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Real-World Evidence Evaluating Teclistamab in Patients with Relapsed/Refractory Multiple Myeloma: A Systematic Literature Review

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Submitted:

09 October 2024

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10 October 2024

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Abstract
Teclistamab (TEC) is the first B-cell maturation antigen-directed bispecific antibody approved by the European Medicines Agency and Food and Drug Administration for triple-class exposed relapsed/refractory multiple myeloma (RRMM). As TEC is increasingly being used in real-world (RW) settings, this study sought to gather existing RW evidence on effectiveness, safety, healthcare resource utilization, and clinical practices associated with TEC. A systematic literature review was performed to identify RW observational studies of adults with RRMM treated with TEC. Sixty-one records representing 41 unique studies were included; sample sizes ranged from 8 to 572 patients. Where reported, median follow-up ranged from 2.3 to 33.6 months and more than 65% of patients would have been ineligible for the pivotal trial of TEC (MajesTEC-1) in all but one study. Across populations with ≥50 patients, overall response rates ranged from 50 to 66% and cytokine release syndrome (CRS) rates ranged from 18 to 64%. Tocilizumab use for CRS management was reported in 14 studies, with two indicating lower CRS rates (13% and 26%) when used prophylactically. Survival and infection outcomes showed wide variability due to short follow-up in most studies. Overall, early RW effectiveness and safety outcomes of TEC were comparable to findings from MajesTEC-1.
Keywords: 
Subject: Medicine and Pharmacology  -   Hematology

1. Introduction

Multiple myeloma (MM) accounted for 1.8% of all cancer diagnoses and 2.0% of deaths in the United States through July, 2024 [1]. While 5-year survival rates of MM have more than doubled since the 1970s [2], the disease is typically characterized by a series of responses and relapses meaning patients ultimately require multiple lines of therapy [3]. It imposes substantial healthcare burden as patients progress through successive lines of therapy; a recent retrospective database study found that all-cause healthcare costs averaged $35,760 per patient per month among patients with four or more prior lines of therapy [4]. After the three main classes of drugs for MM (proteasome inhibitors [PI], immunomodulatory imide drugs [IMiD], and anti-CD38 monoclonal antibodies [CD38 mAb]) have failed patients, few effective options remain for relapsed/refractory multiple myeloma (RRMM). Deciding on next steps in treatment requires clinicians and patients to consider the pace of disease progression, patient comorbid conditions, potential clinically relevant toxicities, and the timing as well as financial implications of treatment [5].
The treatment landscape for RRMM has evolved considerably with the introduction of innovative targeted therapies, including B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR) T-cell and bispecific therapies [6]. Teclistamab-cqyv (TECVAYLI®, Janssen Biotech) is the first-in-class BCMA-targeted bispecific antibody (BsAB) approved by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) in August and October 2022, respectively, for adult patients with RRMM who have previously received at least three prior lines of therapy in Europe or at least four prior lines of therapy in the US, including a PI, IMiD, and CD38 mAb. Teclistamab (TEC) is administered subcutaneously initially using a step-up dosing (SUD) schedule due to the risk of cytokine release syndrome (CRS) and neurotoxicity, followed by weight-based weekly or every-other-week treatment doses; patients must also be monitored longitudinally for infection and receive the recommended prophylaxis. For patients referred by community clinicians to specific centers for TEC SUD, clinicians must then consider how to transition care for patients back to the community setting following SUD. In real-world (RW) practices, clinicians have been exploring different care models for TEC SUD, including outpatient administrations, with the goal of reducing healthcare resource utilization (HCRU) and improving treatment experiences while ensuring patient safety [7,8,9].
MajesTEC-1, the initial phase I/II trial reporting on the efficacy and safety of TEC, demonstrated an overall response rate (ORR) of 63%, including 46% of patients achieving complete response (CR) or better [10,11]. CRS occurred in 72% of patients (most CRS events were grade 1 or 2 in severity while one patient [0.6%] experienced a grade 3 event), and 3% developed immune effector cell-associated neurotoxicity syndrome (ICANS) [10]. MajesTEC-1 utilized stringent eligibility criteria that excluded patients with significant disease burden, such as those with organ dysfunction, poor performance status, serious comorbid conditions, severe cytopenias, and/or prior BCMA-directed therapy exposure; however, these characteristics are common in RW practice [10,12]. As a result, patients treated in MajesTEC-1 may not have been representative of all indicated patients in a RW setting [12]. Several consortia and institutions have disseminated reports on early RW outcomes and safety with TEC; synthesis of these results remains an area of unmet need. As TEC is increasingly being used in RW settings with a growing amount of RW evidence being published, this systematic literature review (SLR) aimed to identify and summarize the latest RW outcomes of TEC, including effectiveness, safety, healthcare provider practices, and associated HCRU.

2. Materials and Methods

This SLR was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [13].
Study eligibility criteria were defined in terms of the population, intervention, comparator, outcome, and study design (PICOS) structure outlined in Supplementary Table A.1, which guided the identification and selection of studies for the SLR. The target population included adult patients (≥18 years) with MM. The only intervention of interest was TEC, but no restrictions were applied to comparators. No restrictions were applied to outcomes to ensure all relevant evidence was captured. Observational RW studies (prospective and retrospective) were included, while clinical trials, pooled analyses of clinical trials, case reports, case series, and narrative reviews were excluded. Publications of SLRs were excluded, but the bibliographies of relevant SLRs were screened for any relevant citations not otherwise captured in the main searches (i.e., these references served only as secondary sources to ensure that all studies meeting the eligibility criteria were identified). Only English-language publications of full-text articles and conference materials (i.e., abstracts, posters, or oral presentations) were included, and a time restriction from the years 2023 to 2024 was applied.
Relevant studies were identified by searching the following databases through the Ovid platform: Medical Literature Analysis and Retrieval System Online (MEDLINE) and Excerpta Medica database (Embase). The specific search algorithms included a combination of indexing and free-text terms (see search terms in Supplementary Table B.1 and Table B.2). The population terms were adapted from existing reviews [14,15], and terms for the generic and brand names of TEC were incorporated.
The main database searches were augmented with searches of 15 specific clinical or managed care conference proceedings from 2023 and 2024 (Supplementary Table C.1). The Northern Light database was used to search for studies from conferences that were indexed in the database (see search terms in Supplementary Table B.3), while conference websites were hand searched for the remaining conferences. Database searches were conducted at the end of May 2024, and further hand searches were conducted through the end of June 2024 to ensure all relevant materials were captured through the first half of 2024.
One reviewer performed all citation screening and data extraction, with quality checks performed by a second reviewer; a third reviewer was included to reach consensus on any remaining discrepancies where necessary. Screening decisions and extracted data were stored and managed in Microsoft Excel (Microsoft, Redmond, Washington, United States). The process of study identification and selection was summarized with a PRISMA flow diagram [13]. Kaplan-Meier (KM) curves for progression-free survival (PFS) and overall survival (OS) were extracted using DigitizeIt (DigitizeIt, Braunschweig, Germany), and reconstructed using an algorithm published by Guyot et al., 2012 [16]. The Newcastle-Ottawa Scale (Ottawa Hospital Research Institute, Ottawa, Canada) was used to assess the quality of observational studies where full-text publications were available (Supplementary Table D.1). The scale utilizes a 'star system' to judge (i) the selection of the study groups; (ii) the comparability of the groups; and (iii) the ascertainment of either the exposure or outcome of interest for case-control or cohort studies respectively.

3. Results

3.1. Study Characteristics

Of the 156 records identified across all sources, a total of 61 publications (five full-texts [12,17,18,19,20] and 56 conference abstracts, posters, or oral presentations) representing 41 unique studies evaluating TEC in a RW setting were identified (Figure 1); these are summarized in Table 1. The included studies spanned seven countries in North America and Europe. Thirty-five of the 41 studies were retrospective in design. Fifteen studies (36.6%) reported results pooled from multiple centers while 25 studies (61.0%) reported experience from a single center. The majority of studies (n=34) were chart reviews and seven studies reported data gathered from secondary databases. In 40 studies, sample sizes ranged from 8 to 572 patients. One study using the FDA Adverse Event Reporting System database reported 719 adverse event (AE) cases of TEC, rather than the event rates among patients, and therefore was not included in the results summary [21]. Median follow-up (mFU) duration was reported in 19 studies (46.3%) and ranged from 2.3 [22] to 33.6 months [23]. ORR and CRS rates were the most frequently reported effectiveness and safety measures, respectively. AE management using tocilizumab (TCZ), length of hospital stay during TEC SUD, ICANS, and infections were also frequently reported. Common subpopulations included patients with prior anti-BCMA exposure and outpatient SUD. Studies that included other interventions alongside TEC were included when TEC only subpopulation data were available (labeled as “TEC treatment group” in subsequent tables). Based on the Newcastle-Ottawa Scale, the five included full-text publications [12,17,18,19,20] were high quality in terms of study population selection and ascertainment of outcomes; all five studies had a non-comparative design so could not be compared directly.

3.2. Population Characteristics

Population characteristics are reported in Table 2 and Table 3; additional characteristics are available in Supplementary Table E.1 and Table E.2. Within the overall populations, median age ranged from 64 [38] to 75 [54] years, and 45.6% [44] to 91.2% [33] of patients were White. High-risk cytogenetic abnormalities were reported in 21 studies and were present in 21.7% [59] to 84.6% [42] of patients. Thirteen studies consistently defined high-risk cytogenetics as having one of the following abnormalities: del17p, t(4;14), or t(14;16); nine of these studies included 1q gain/amp, six studies included t(14;20) [7,18,19,42,66,71], one study included TP53 mutations [48], and one study included monosomy 17 [66]. The remaining eight studies did not provide a definition.
Extramedullary disease (EMD) was present in 6% [7,26] to 77% [53] of patients in 17 chart review studies, where documented. One study utilizing data from a French post-marketing access program (Acces précoce) found EMD was present in 21% of patients [59], and one study utilizing data from a multi-center MM electronic medical record (EMR) database reported that EMD diagnosis codes were present in 5.7% of patients [26]. Of these studies, 11 did not provide a definition for EMD; four of the remaining studies defined EMD as any plasmacytomas [7,17,26,42] and four defined EMD as plasmacytomas not associated with bone [12,19,66,71]. Median number of prior lines of therapy ranged from 4 [50,55,59] to 7 [17,24,38,46], which included patients with prior BCMA-directed therapy exposure. Other prior lines of therapy can be found in Supplementary Table E.1.
MajesTEC-1 ineligibility was reported in eight studies, where more than 65% of patients were ineligible in seven of these (87.5%); one study reported 39% of patients as ineligible [62]. The most common reasons for ineligibility in these studies included prior BCMA-directed therapy (13% [53] to 100% [46]), poor performance status (Eastern Cooperative Oncology Group [ECOG] ≥2; 29.8% [44] to 52% [53]), cytopenia(s) (31% [12] to 48.3% [44]), and/or renal impairment/failure (12% [66] to 32.6% [24]). Additionally, individual cytopenia ranges across all studies included anemia (22.6% [46] to 59.3% [25]), neutropenia (2% [12] to 28.6% [7]), and thrombocytopenia (20% [12] to 32.3% [46]).

3.3. Outcomes

The following sections summarize the most frequently reported outcomes of interest for the overall populations in the included studies, focusing on the most recent timepoint in each study.

3.3.1. Effectiveness Outcomes

Twenty studies reported on effectiveness outcomes (Table 4 and Figure 2) and wide variability in response and survival rates was observed across these studies. Among larger studies that included at least 50 patients, ORR (partial response [PR] or better) ranged from 50% [44] to 66% [12] (n=7 studies), very good partial response (VGPR) or better ranged from 24% [44] to 51% [19] (n=6 studies), and CR or better ranged from 19% [66] to 29% [12] (n=4 studies).
The variability in PFS and OS across all studies is shown in Figure 2. Of the studies with at least 50 patients (n=6 studies; mFU 2.3 [22] to 5.5 [20] months), median PFS ranged from 2.8 [44] to 13 [66] months and was not reached in one study [19]. The 6-month PFS rate was similar across studies where reported (52% [19] to 58% [66] in three studies; mFU 3.5 [19] to 9.5 [71] months). Among larger studies with at least 50 patients, median OS was not reached in four studies (mFU 3.5 [19] to 5.5 [20] months) while one reported a median of 15 months (mFU 5 [66] months). The 6-month OS rate ranged from 70% [12] to 80% [19] (n=3 studies; mFU 3.5 [19] to 5 [66] months).

3.3.2. Safety Outcomes

Safety outcomes were reported in 33 studies (Table 5) with wide variability in the proportion of patients experiencing AEs observed across all studies. Of these, 28 studies reported CRS rates, 17 studies reported ICANS rates, and 12 studies reported infection rates in the overall population. Among the larger studies with at least 50 patients, the proportion of patients who developed any grade CRS ranged from 18% [26] to 64% [12,18] (n=11 studies), and a small proportion of patients (0.5% [66] to 4.5% [19]) experienced grade 3 CRS (n=7). When stratified by data source and care models, any grade CRS rates from chart reviews of patients with inpatient monitoring ranged from 40% [56] to 64% [12], and CRS rates from secondary databases (e.g., payer claims, EMRs) ranged from 18.4% [26] to 41.2% [25], as identified by the International Classification of Diseases 10th Revision codes. Five studies reported any grade ICANS rates ranging from 4% [26] to 14% [12] and three studies reported grade 3 ICANS rates ranging from 0% [26] to 4.5% [19]. Any grade infections were experienced by 31% [12] to 60% [66] of patients (n=5 studies), and approximately 26% of patients had grade 3 infections (n=2 studies) [19,20]. There was a much broader range in CRS, ICANS, and infection rates when considering studies with smaller sample sizes. Two studies reported the impact on CRS rates when using prophylactic TCZ [53,56], as described in more detail below.
The most frequently reported healthcare outcome related to provider practices was TCZ use in AE management, which was reported in 12 studies. Among seven studies with at least 50 patients, TCZ usage ranged from 10% [69] to 41% [12] in the overall population. Additionally, two studies with any sample size reported on prophylactic TCZ use. Kowalski 2023 only included patients (n=31) treated with prophylactic TCZ before TEC treatment, and there was a CRS rate of 13% (all grade 1; 95% CI 4, 30; p < 0.01) [53]. Within an inpatient setting, Marin 2023 assessed patients treated with prophylactic TCZ prior to the second TEC SUD (n=38) and compared them to a cohort of patients who received TEC without prophylactic TCZ (n=15) [56]. The cohort with prophylactic TCZ had a 26% rate of any grade CRS (21% grade 1), while the cohort without prophylactic TCZ had a much higher rate of 73% any grade CRS (67% grade 1) [56].
The most frequently reported HCRU outcome was hospital length of stay (LOS) during TEC SUD for TEC administration or AE management if admitted after an outpatient administration. Four studies with at least 50 patients reported an inpatient SUD administration model, with the median LOS ranging from 8 days [26,66] to 9 days [12,57]. Two studies, both with sample size of at least 50, reported on mean LOS during SUD with values of 8.6 (SD 1.7) days [69] and 8.5 (SD 3.0; extreme outliers excluded) days [25]. Two studies with any sample size reported separate LOS data for day 1-3-5 and day 1-4-7 dosing schedules. Kawasaki 2024 reported a mean 7.6 and 9.2 days for the 1-3-5 and 1-4-7 schedules, respectively, and Graf 2024 reported a median 6 and 9 days for the 1-3-5 and 1-4-7 schedules, respectively. Additionally, three studies (any sample size) with patients undergoing outpatient SUD reported LOS for admissions at any time due to AEs, with medians of 1.5 days [28], 2 days [58], and 4 days [51] per admission.
Two studies reported that LOS for SUD decreased over time: Banerjee 2023a, using nationally representative payer claims data, reported a mean LOS of 11.4 (SD 9.0) days for patients who initiated TEC within the first four months of FDA approval (through February 2023), and a mean LOS of 7.0 (SD 1.4) days for patients who initiated TEC in the most recent month (July 2023 by the data cut-off) [25]. Similarly, Banerjee 2023b, using a multi-center MM EMR database, reported a median LOS of 11 days in December 2022, and a median LOS of 6.5 days in May 2023 [26].
Three recently published studies reported the proportion and timing of patients switching from weekly dosing to less frequent dosing (e.g., every-other-week). Tan 2024 reported that 32 patients (37%) switched at a single academic center with a median time to switch of 3.3 months [71]. Additionally, given most patients switched after reaching a desired response, an high ORR was observed (94%); after a median follow-up of 6.4 months after switching, 6-month PFS rate post-switch was 90%, indicating that patients maintained response after switching [71]. Two studies, using nationally representative secondary data, estimated the probability and timing of patients switching to less frequent dosing using KM analysis. The probability of switching to less frequent dosing at three months was 15.5% [27] and 19.0% [60], and this increased to 38.3% [27] and 38.6% [60] at six months. The median time to switch was 8.5 months in one study [27], and was not reached at mFU of 4.2 months in the other [60].

4. Discussion

This is the first SLR to consolidate RW studies of TEC globally. Wide variance was seen in the effectiveness and safety of TEC across the entire evidence base, with ORR ranging from 44% to 87%, CRS rates of 6% to 85% depending on data sources and care models, and ICANS being present in 0% to 23% of patients. When restricting to larger studies that included at least 50 patients, the range of results narrowed: ORR ranged from 50% to 66%, CRS rates ranged from 18% to 64% depending on data sources and care models, and ICANS rates ranged from 4% to 14%. Wide variability in PFS and OS estimates and limited data on infection was observed given short follow-up time in most studies, and this trend was still observed when only considering studies with larger sample sizes. Early RW use of TEC was characterized by administration to a diverse group of patients, including minorities, patients with significant comorbid conditions, high-risk features, and those with prior BCMA-directed therapy exposure.
The collation of these data provides early insight into how RW outcomes of TEC compare with the results of the MajesTEC-1 trial, taking into account that most RW studies reported more than half of patients would have been ineligible for the MajesTEC-1 trial. Patients in the RW differ from the trial populations since they are not required to meet stringent eligibility criteria and may have more comorbidities and less hematopoietic or organ reserve [10,12]. Additionally, with TEC being a first-in-class BCMA BsAB and these studies capturing data from the first year since TEC approval, the patients included in RW studies may have had advanced disease and may have been more heavily pretreated. Despite this, the early effectiveness and safety profile of RW TEC appeared comparable with MajesTEC-1.
The ORR in MajesTEC-1 was 63% [10]; studies evaluating ORR in this SLR also provided similar results with RW evidence showing a range of 50% [44] to 66% [12] among studies with at least 50 patients. Despite the similarities in ORR, depth of response differed in the early RW patients. In MajesTEC-1, 45.5% of patients achieved a response of CR or better [10], whereas the CR rates ranged from 19% [66] to 29% [12] in the early RW setting. The RW CR or better rate is likely a reflection of the hard-to-treat population which included those with heavily pretreated disease, high-risk features, significant comorbidities, and/or those with prior exposure to BCMA-directed therapy. Additionally, many RW patients may have not undergone bone marrow biopsies or 24-hour urine samples to confirm International Myeloma Working Group CR status, which would have been further categorized as having a VGPR and resulted in an underestimated rate of CR or better. Moreover, the short follow-up in the RW studies may have limited the ability to assess for deep responses due to delayed clearance of paraprotein following tumor killing [75]. Given the median time to best response in MajesTEC-1 was 3.8 months [10], the RW studies with short follow-up durations were unable to effectively measure best response, PFS or OS. Furthermore, clarifying the duration between the patient’s prior BCMA-directed therapy and the first TEC dose in patients with prior exposure to BCMA-directed therapy will also be paramount to interpreting their survival outcomes.
The rate of any grade CRS in the MajesTEC-1 clinical trial was 72% [10], which was greater than the range reported in RW studies with at least 50 patients (18% [26] to 64% [12,18]). Additionally, the CRS rates in RW studies that used prophylactic TCZ (13% and 26%) [53,56] were similar to the subgroup in the MajesTEC-1 cohort that received prophylactic TCZ (26%) [76]. There was notable variation in CRS rates across the included studies, possibly due to differences in data sources, data collection methods, and the care models for CRS prophylaxis and monitoring. Patients found within secondary databases (e.g., payer claims, EMR) are expected to have lower rates due to their reliance on diagnostic codes; for example, healthcare professionals may not be coding fever as CRS or coding fever at all, and diagnosis codes specifically for CRS may not always been used. Chart reviews of patients with inpatient monitoring may represent a more stringent definition of RW CRS rates with TEC, i.e., data are directly from physician’s notes and CRS-relevant signs and symptoms are continuously monitored and recorded systematically in the hospital setting. Data on patients who received outpatient monitoring tend to have lower rates compared to inpatient monitoring as they may have different triggers and thresholds of CRS reporting, and sometimes may rely on patient-reported symptoms. These differences in data sources and settings differ from the MajesTEC-1 trial as well, and therefore should be considered while interpreting results.
Studies included in the SLR also did not report if general neurotoxicity and ICANS were assessed together or if the reported value was ICANS alone. Including neurotoxicity with ICANS may explain the higher rate of ICANS in the RW setting (4% [26] to 14% [12] in studies with at least 50 patients) versus that observed in MajesTEC-1 (3%), as neurotoxicity symptoms cover a wide spectrum and definitions vary across practices.
Infection rates were sparsely reported across the RW studies which limited the ability to analyze these data; among the larger studies, only five studies reported any grade infections (31% [12] to 60% [66]) and only two studies reported grade ≥3 infections (26% [19] and 27% [20]). MajesTEC-1 reported a higher rate of infections (76%) with 45% of patients experiencing grade 3 or 4 infections [77], though this was with longer follow-up. Unlike CRS and ICANS, which occur at the beginning of treatment and are less dependent on follow-up times in RW studies, infection risk persists throughout treatment, so studies with shorter follow-up times may report lower rates. Additionally, as TEC was the first BCMA BsAB treatment and because MajesTEC-1 enrolled patients concurrently with the onset of the COVID-19 pandemic before widespread vaccine availability, infection management could be different in the post-pandemic period; therefore, the infection rates in the RW should not be directly compared with MajesTEC-1. Guidelines agreed upon by expert consensus have since been published, allowing for optimal treatment of infections during TEC treatment [77,78]. With adoption of infection management guideline recommendations for MM, other reasons for lower RW infection rates could be routine vaccination against COVID-19 and prophylactic intravenous immunoglobulin use for hypogammaglobulinemia and antibiotic use. Given the short follow-up durations, data on long-term infection prophylaxis and management will need to be assessed in future work.
Large chart review studies conducted in multiple centers may be more generalizable to the wider population. Five multi-center chart review studies with sample sizes ≥50 patients (Supplementary Table F.1) demonstrated relatively consistent ORR and lower CRS rates than MajesTEC-1 despite a high proportion of ineligible patients. Short follow-up times hinder the comparability of these studies to MajesTEC-1 for several outcomes, especially OS, PFS, and infections. Future analyses may address this issue as data-cuts with longer follow-up are released.
This review also provides initial insights into healthcare provider practices and HCRU associated with TEC in the RW setting. The use of TCZ during SUD and other medications often used for managing AEs associated with TEC were frequently reported in the studies included in the SLR. Although preliminary results showed benefits of using prophylactic TCZ in Marin 2023 [56] and Kowalski 2023 [53], further studies with larger sample sizes are warranted. Based on studies published in 2023 and the first half of 2024, most patients received TEC SUD in an inpatient setting, with some institutions starting to implement outpatient SUD models [7,9,28,50,66]. This is reflected in a recent study that conducted a panel interview of clinicians from 20 practices across 13 states who were among the first ones to start TEC in their practices after FDA approval. Within seven months of approval, 74% of these practices provided SUD exclusively in an inpatient setting, while 26% provided SUD in an outpatient or hybrid setting; all participating practices using inpatient SUD expressed desire of moving to outpatient SUD for BsAb in the future [79]. In two secondary database analyses that monitored inpatient LOS for SUD over time, a decreasing trend was observed [25,26]. This observation might be due to improved familiarity with TEC among providers over time, availability of well-established AE management protocols, and quality improvement models that institutions might have implemented to reduce HCRU. Furthermore, two studies using large databases of medical records suggest that patients were able to complete SUD without delay with the two-day and three-day dosing schedules being the most common and that the majority of patients were taking pre-medications as recommended [26,69].
Recent studies with RW data available for patients who switched to a less frequent dosing schedule (e.g., every-other-week) have shown results in line with the MajesTEC-1 trial. In MajesTEC-1, patients were allowed to switch from weekly TEC doses to every-other-week if they achieved a PR or better after four or more cycles in the first phase or a CR or better for six or more months in the second phase [10,11]. With over two years of follow-up, TEC demonstrated deep and durable responses and reduced new onset grade ≥3 infections over time, including in patients who switched to less frequent dosing [11]. The reduction in new onset grade ≥3 infections may also be impacted by increasing usage of IVIG and prophylaxis [11]. Three RW studies identified in the SLR reported on less frequent TEC dosing, mainly with an every-other-week schedule among patients who switched [27,60,71]. Monthly dosing was observed rarely within these studies, and the median time to switch varied from 3.3 months [71] to 8.5 months [27] (not reached in one study at mFU of 4.2 months [60]). Of note, Tan 2024 reported a high 6-month PFS rate (90%) from the date of switching to less frequent dosing and concluded that less frequent dosing was feasible in patients who responded and could also be used for safety management [71]. Future research with longer follow-up and larger sample sizes is needed to further understand effectiveness and safety associated with less frequent dosing, as well as the optimal timing of switching.
This SLR has some limitations. First, the recent approval of TEC resulted in the restriction of studies to the 2023 and 2024 calendar years, leading to an evidence base consisting of mostly conference materials with only five full-texts. As conferences abstracts may not include as detailed information as full-text publications, these results should be interpreted with caution. Due to the publication date restriction, most studies included patients who initiated TEC within 1 year of approval, which resulted in short follow-up periods and small sample sizes, and more time is needed for the long-term outcomes to mature. Many of these early patients were expected to be sicker with higher disease burden, which explains the high percentage of reported MajesTEC-1 ineligibility. Despite this, the early effectiveness and safety outcomes remain consistent with the clinical trial. When sample sizes allow, results may be stratified by MajesTEC-1 eligibility to provide a more balanced comparison with clinical trial results. Further, given the short follow-up periods, outcomes such as PFS, OS, and infection rate often need to be considered carefully as current data may not reflect true estimates over time. Finally, numbers at risk over time or total number of events are needed for reasonable accuracy during KM curve extraction and recreation [16], but this information was not available in several studies. As a result, comparisons made through the KM curves are limited and need to be interpreted cautiously. These limitations are further affected by a wide variation in data due to differences in sample sizes, differences in data sources, and differences in RW clinical practices across health centers. Due to these limitations, a meta-analysis with patient-level data would be an appropriate next step once data matures.

5. Conclusions

In conclusion, this SLR summarizes the initial RW evidence available for TEC. Variation and immature data limits the interpretation of long-term outcomes; however, results from studies with larger sample sizes suggest that the early effectiveness and safety profiles for TEC in the RW are comparable to those from the pivotal trial, even for patients who were sicker, with high disease burden, and would not have met eligibility criteria for MajesTEC-1.

Author Contributions

Conception and design: BD, FRW, DL, BW, MF, JF, APS, NK, MD, AM, JC, and SK. Data collection: IS, FRW, DL, BW, and NK. Analysis and interpretation of results: All authors. Manuscript writing: All authors. All authors have read and agreed to the published version of the manuscript.

Funding

This study was sponsored by Janssen Scientific Affairs, LLC.

Data Availability Statement

All data generated or analyzed during this study are included in this published article and its supplementary information files.

Acknowledgments

Additional contributions by those who do not meet authorship requirements include Dylan McLoone for the creation of the KM curve overlays and Carole Lunny for data extraction and QC.

Conflicts of Interest

B Derman is an employee of UChicago Medicine; and declares consulting services for Janssen Scientific Affairs, Cota Healthcare, Guidepoint Global, Gerson Lehrman Group, Precision AQ, Sanofi, and Canopy; and honoraria from OncLive/MJH Life Sciences, Plexus, and Multiple Myeloma Research Foundation; and research funding from GlaxoSmithKline and Amgen. C Tan is an employee of Memorial Sloan Kettering Cancer Center; and declares consulting services for Janssen Medical Affairs and Sanofi; honoraria from MJH Life Sciences; and may hold stock and other ownership interests in Johnson & Johnson/Janssen, Moderna Therapeutics, ImmunityBio, Nektar, and Pfizer; and research funding from Janssen and Takeda. I Steinfield, FR Wilson, and S Keeping are employees of Precision AQ. D Lin, B Wu, M Fernandez, J Fowler, A Paner-Straseviciute, N Kim, M Doyle, A Marshall, and J Cheadle are employees of Johnson & Johnson Innovative Medicine and may hold stock or stock options of Johnson & Johnson. JJ Liu is an employee of Illinois Cancer Care.

Appendix A – PICOS Criteria.

Table A.1. Eligibility criteria for systematic literature review.
Table A.1. Eligibility criteria for systematic literature review.
Criteria Inclusion Exclusion
Population Adult (≥18 years) patients with multiple myeloma Patients aged <18 years
Interventions Teclistamab Interventions not listed
Comparators No restrictions --
Outcomes No restrictions --
Study design Real-world observational studies (prospective, retrospective) Clinical trials
Case reports or case series
Pooled analyses of trials
Systematic literature reviewsa
Non-systematic/narrative reviews
Publication type Full text publications
Conference abstracts/postersb 		Letters to editors
Editorials
Commentary
Expert opinion
Guidelines
Language Only studies published in English Studies published in a language other than English (even if abstract is in English)
Time Published between 2023 and 2024 Published before 2023
Notes: Double dashes (“—“) indicate data not reported. a) Systematic reviews were excluded, but bibliography of relevant systematic reviews were reviewed to capture relevant citations; b) Conference abstract/poster citations captured through search of Embase were screened, and conferences of interest were also searched separately in the Northern Light database or published proceedings from target conferences.

Appendix B – Literature Search Strategies

Table B.1. Search strategy for Embase.
Table B.1. Search strategy for Embase.
Database: Embase 1974 to May 22, 2024
Search executed on May 23, 2024
# Criteria Search terms Results
1 Population terms exp multiple myeloma/ 102,883
2 exp plasmacytoma/ 14,274
3 exp Paraproteinemias/ 183,815
4 (myeloma or (multiple adj2 myeloma$) or plasmacytom$ or plasmocytom$ or mgus or (monoclonal adj2 gammopath$)).mp. 149,247
5 or/1-4 221,071
6 Intervention terms exp teclistamab/ 406
7 (teclistamab or Tecvayli or JNJ-64007957 or teclistamab-cqyv).mp. 424
8 or/6-7 424
9 SIGN filters for observational studies Clinical study/ 166,793
10 Case control study/ 217,895
11 Family study/ 25,824
12 Longitudinal study/ 213,746
13 Retrospective study/ 1,624,202
14 Prospective study/ 919,580
15 Randomized controlled trials/ 274,328
16 14 not 15 908,367
17 Cohort analysis/ 1,167,616
18 (Cohort adj (study or studies)).mp. 517,217
19 (Case control adj (study or studies)).tw. 176,157
20 (follow up adj (study or studies)).tw. 76,223
21 (observational adj (study or studies)).tw. 276,600
22 (epidemiologic$ adj (study or studies)).tw. 125,861
23 (cross sectional adj (study or studies)).tw. 373,627
24 (retrospective adj7 (study or studies or design or analysis or analyses or cohort or data or review)).ti,ab. 1,254,000
25 or/9-13,16-24 4,466,453
26 Combined criteria 5 and 8 and 25 96
27 Language filter limit 26 to english language 96
28 Date filter limit 27 to yr=”2023 -Current” 72
Note: Embase search was performed again at the end of June 2024 and no additional, relevant publications were identified.
Table B.2. Search strategy for MEDLINE.
Table B.2. Search strategy for MEDLINE.
Database: Ovid MEDLINE(R) ALL <1946 to May 22, 2024>
Search executed on May 23, 2024
# Criteria Search terms Results
1 Population terms exp multiple myeloma/ 49,135
2 exp plasmacytoma/ 8,932
3 exp Paraproteinemias/ 64,055
4 (myeloma or (multiple adj2 myeloma$) or plasmacytom$ or plasmocytom$ or mgus or (monoclonal adj2 gammopath$)).mp. 84,636
5 or/1-4 96,987
6 Intervention terms (teclistamab or Tecvayli or JNJ-64007957 or teclistamab-cqyv).mp. 89
7 SIGN filters for observational studies Epidemiologic studies/ 9,543
8 exp case control studies/ 1,506,567
9 exp cohort studies/ 2,607,741
10 Case control.tw. 162,188
11 (cohort adj (study or studies)).tw. 351,806
12 Cohort analy$.tw. 13,035
13 (Follow up adj (study or studies)).tw. 58,204
14 (observational adj (study or studies)).tw. 178,369
15 Longitudinal.tw. 345,820
16 Retrospective.tw. 812,750
17 Cross sectional.tw. 562,700
18 Cross-sectional studies/ 502,656
19 or/7-18 4,003,471
20 Combined criteria 5 and 6 and 19 11
21 Language filter limit 20 to english language 11
22 Date filter limit 21 to yr="2023 -Current" 11
Table B.3. Search strategy for Northern Light Life Sciences Conference Abstracts.
Table B.3. Search strategy for Northern Light Life Sciences Conference Abstracts.
Database: Northern Light Life Sciences Conference Abstracts 2010 - 2024 Week 20
Search executed on May 23, 2024
# Criteria Search terms Results
1 Population terms exp multiple myeloma/ 27388
2 exp plasmacytoma/ 1694
3 exp Paraproteinemias/ 30424
4 (myeloma or (multiple adj2 myeloma$) or plasmacytom$ or plasmocytom$ or mgus or (monoclonal adj2 gammopath$)).mp. 30055
5 or/1-4 32556
6 Intervention terms (teclistamab or Tecvayli or JNJ-64007957 or teclistamab-cqyv).mp. 102
7 Conference filter Academy of Managed Care Pharmacy.cf. 2749
8 American Society of Clinical Oncology.cf. 79140
9 American Society of Hematology.cf. 66037
10 European Hematology Association.cf. 31727
11 European Society for Medical Oncology.cf. 22763
12 International Myeloma.cf. 2497
13 Oncology Nursing Society.cf. 1267
14 Society of Hematologic Oncology.cf. 2052
15 or/7-14 208232
16 Combined criteria 5 and 6 and 15 82
17 Date filter limit 16 to yr="2023 -Current" 47

Appendix C – List of Conferences Searched

Table C.1. Conferences searched in systematic literature review.
Table C.1. Conferences searched in systematic literature review.
Conference Dates held Search method
Academy of Managed Care Pharmacy (AMCP) Meeting March 21-24, 2023
April 15-18, 2024		 Northern Light database via OvidHand search of website
AMCP Nexus October 16-19, 2023 Hand search of website
American Society for Transplantation and Cellular Therapy (ASTCT) and Center for International Blood and Marrow Transplant Research (CIBMTR) Tandem Meeting February 15-19, 2023
February 21-24, 2024		 Hand search of website
American Society of Clinical Oncology (ASCO) Annual Meeting June 2-6, 2023May 31-June 4, 2024 Northern Light database via OvidHand search of website
American Society of Hematology (ASH) Annual Meeting December 9-12, 2023 Hand search of website
European Hematology Association (EHA) Annual Congress June 8-11, 2023
June 13-16, 2024		 Northern Light database via Ovid
Hand search of website
European Society for Medical Oncology (ESMO) October 20-24, 2023 Northern Light database via Ovid
European Myeloma Network (EMN) meeting April 20-22, 2023
April 18-20, 2024		 Hand search of website
Hematology/Oncology Pharmacy Association (HOPA) Annual Conference March 29-April 1, 2023
April 3-6, 2024		 Hand search of website
International Conference on Oncology and Research Treatment (ORT) November 30-December 1, 2023 Hand search of website
International Myeloma Society (IMS) Annual Meeting September 27-30, 2023 Northern Light database via Ovid
Journal of the Advanced Practitioner in Oncology (JADPRO) Live November 9-12, 2023 Hand search of website
Lymphoma, Leukemia & Myeloma (LL&M) Congress October 18-21, 2023 Hand search of website
Oncology Nursing Society (ONS) Congress April 26-30, 2023
April 24-28, 2024		 Northern Light database via Ovid
Hand search of website
Society of Hematologic Oncology (SOHO) Annual Meeting September 6-9, 2023 Northern Light database via Ovid

Appendix D – Risk of Bias Assessment

Table D.1. Newcastle-Ottawa quality assessment scale – cohort studies.
Table D.1. Newcastle-Ottawa quality assessment scale – cohort studies.
Domain Response
Selection
1. Representativeness of the exposed cohort Truly representative of the average _______________ (describe) in the community*
Somewhat representative of the average ______________ in the community*
Selected group of users (e.g. nurses, volunteers)
No description of the derivation of the cohort
2. Selection of the non-exposed cohort Drawn from the same community as the exposed cohort*
Drawn from a different source
No description of the derivation of the non-exposed cohort
3. Ascertainment of exposure Secure record (e.g. surgical records)*
Structured interview*
Written self-report
No description
4. Demonstration that outcome of interest was not present at start of study Yes*
No
Comparability
1. Comparability of cohorts on the basis of the design or analysis Study controls for _____________ (select the most important factor)*
Study controls for any additional factor (this criteria could be modified to indicate specific control for a second important factor)*
Outcomes
1. Assessment of outcome Independent blind assessment*
Record linkage*
Self-report
No description
2. Was follow-up long enough for outcomes to occur Yes (select an adequate follow up period for outcome of interest)*
No
3. Adequacy of follow up of cohorts Complete follow up - all subjects accounted for*
Subjects lost to follow up unlikely to introduce bias - small number lost - >____% (select an adequate %) follow up, or description provided of those lost)*
Follow up rate <____% (select an adequate %) and no description of those lost
No statement
Note: A study can be awarded a maximum of one star for each numbered item within the selection and exposure categories. A maximum of two stars can be given for comparability.

Appendix E – Additional Patient Characteristics and Effectiveness Outcomes

Table E.1. Summary of prior lines of therapy.
Table E.1. Summary of prior lines of therapy.
Study ID Overall / subgroup details n Prior BCMA CAR T, n (%) Prior BCMA ADC, n (%) Prior BCMA BsAB, n (%) Prior non-BCMA, n (%) Prior AlloSCT, n (%) Prior AutoSCT, n (%) Triple-class, n (%) Penta-class, n (%)
CAR-T BsAB Exposed Refractory Exposed Refractory
Asoori 2023 Overall 46 9 (19.6)a 4 (8.7)a 3 (6.5)a -- -- -- -- -- 41 (89.1) -- --
Banerjee 2023a Overall 92 8 (8.7) 9 (9.8)b -- -- -- 43 (46.7) -- -- -- --
Banerjee 2023b Overall 247 27 (10.9) 25 (10.1) 1 (<1) -- -- -- -- -- -- -- --
Bansal 2024 TEC treatment group 48 20 (71.4) -- -- -- -- -- -- -- -- -- --
Dima 2023 Overall 106 -- -- -- -- -- 3 (3) 61 (58) -- 97 (92) -- 68 (64)
>70 years old 33 -- -- -- -- -- -- 19 (58) -- 32 (97) -- 19 (58)
Patients with EMD 45 -- -- -- -- -- -- 29 (64) -- 42 (93) -- 26 (58)
Faiman 2023 Overall 26 -- 1 (3.8)a -- -- -- 10 (38)c -- 26 (100) -- (92)
Firestone 2023 Overall 52 19 (37) 16 (31) 2 (4) 3 (6) 5 (10) 3 (6) 40 (77) 50 (96) -- -- 35 (67)
Ghamsari 2024 Overall 18 5 (27.8)a 2 (11.1)a -- -- -- -- -- -- 18 (100.0) -- 17 (94.4)
Gordon 2023 Overall 58 12 (20.7) 15 (25.9)b -- -- -- 2 (3.4) 40 (69) 58 (100.0) -- 42 (72.4) --
Graf 2024 Overall 25 -- -- -- --- -- -- -- -- 20 (80) -- 12 (48)
Grajales-Cruz 2023 Overall 36 26 (72.2) 4 (11.1) -- -- -- -- 25/33 (75.8)c -- 35 (97.2) -- 22 (61.1)
Hamadeh 2024 Overall 72 19 (27.5)d -- 3 (4.2)d 2 (2.8)d,e 7 (9.7)d,f 5 (6.9)d 48 (66.7)d -- -- -- --
Prior TCRT 27 19/21 (90) -- 3/10 (30) 2/21 (10)e 7/10 (70)f 3 (11) 19 (70) -- -- -- --
No prior TCRT 45 -- -- -- -- -- 2 (1) 29 (64) -- -- -- --
Howard 2023 Overall 23 -- -- -- -- -- 1 (4) 16 (70) -- 20 (87) -- 10 (43)
Kawasaki 2024 Overall 27 -- -- -- -- -- -- 18 (66.7) -- 27 (100.0)d -- --
Dosing schedule 1, 3, 5 (days) 23 -- -- -- -- -- -- 15 (65) -- 23 (100) -- --
Dosing schedule 1, 4, 7 (days) 4 -- -- -- -- -- -- 3 (75) -- 4 (100) -- --
Kowalski 2023 Overallg 31 -- -- -- -- -- 12 (39)h 31 (100) 26 (84) 21 (68) 6 (19)
Marin 2023 Overal 53 -- -- -- -- -- -- -- -- 53 (100.0)d,i -- --
No prophylactic TCZ 15 -- -- -- -- -- -- -- -- 15 (100.0)i -- --
Prophylactic TCZ 38 -- -- -- -- -- -- -- -- 38 (100.0)i -- --
Midha 2023 Overall 56 13 (23.2) 12 (23.2) -- -- -- 33 (58.9)j -- -- -- --
Mohan 2024 Overall 110 -- -- -- -- -- -- 96 (87) -- 95 (86) -- 84 (76)
Perrot 2023 Overall 572 -- -- -- -- -- -- -- -- 398k (69.6) -- 183k (32.0)
Pianko 2024 Overall 419 51 (12.2) 71 (16.9) 0 (0.0) -- -- -- -- -- -- -- --
Reidhammer 2024 Overall 123 21 (17.1)a,l 23 (18.7)a -- -- -- -- -- -- 114k (92.6) -- 74k (60.2)
Sandahl 2023 Overall 49 10 (20.4) 5 (10.2) -- -- -- -- -- -- -- -- --
Schaefers 2023 Overall 16 -- -- -- -- -- -- -- -- -- -- 16 (100)
Tabbara 2024 Overall 25 1 (4) -- -- -- -- 13 (52)j -- -- -- --
Tan 2023a Overall 204 40 (19.6)a 25 (12.3)a 5 (2.5)a -- -- -- -- -- 123/156 (79.0) -- 56/150 (37.0)
Tan 2024 Overall 86 21/32 (66) 19/32 (60) 3/32 (9) -- -- 3 (3) 53 (62) -- -- -- --
Venkatesh 2023 Overall 22 -- -- -- -- -- 17 (77)j -- 20 (91) -- 13 (59)
Notes: Double dashes (“—“) indicate data not reported. Table only includes studies where the relevant characteristics were reported. a) % hand calculated; b) Reported as belantamab; c) Reported as HSCT; d) Calculated from stratified cohorts; e) Includes 1 (5%) GPRC5D and 1 (5%) CD38-targeted CAR-T therapy; f) Includes 3 (30%) GPRC5D and 4 (40%) FcRH5-targeted BsAB therapies; g) Overall population was treated with prophylactic tocilizumab; h) Reported as SCT; i) IMID, PI and CD38 mAb refractory; j) Allogenic or autologous not distinguished; k) n hand calculated; l) Reported as ide-cel. Abbreviations: ADC, antibody-drug conjugate; AlloSCT, allogenic stem cell transplant; AutoSCT, autologous stem cell transplant; BCMA, B-cell maturation antigen; BsAB, bispecific antibody; CAR-T, chimeric antigen receptor t-cell; CD-38, cluster of differentiation 38; EMD, extramedullary disease; GPRC5D, G protein–coupled receptor, class C, group 5, member D; IMID, immunomodulatory imide drugs; HSCT, hemopoietic stem cell therapy; mAb, monoclonal antibody; PI, proteasome inhibitors; SCT, stem cell therapy; TCRT, T-cell redirection; TCZ, tocilizumab; TEC, teclistamab.
Table E.2. Summary of comorbidities at baseline.
Table E.2. Summary of comorbidities at baseline.
Study ID Overall / subgroup details Sample size Hemodialysis/ dialysis, n (%) Peripheral neuropathy, n (%) Hypogamma-globulinemia, n (%) CNS involvement, n (%)
Asoori 2023 Overall 46 2 (5.4) -- 32 (69.6) --
Banerjee 2023a Overall 124 9 (4.9) 57 (31.3) 52 (28.6) --
Banerjee 2023b Overall 247 -- 89 (36) 39 (15.8) --
Dima 2023 Overall 106 -- -- -- 4 (4)
Grajales-Cruz 2023 Overall 33 -- -- 17 (53.1) --
Kowalski 2023 Overallb 31 -- -- -- 2 (7)
Lachenal 2023 Overall 15 15 (100)c -- -- --
Midha 2023 Overall 56 -- -- -- 7 (12.5)
Pianko 2024 Overall 419 -- -- 125 (29.8) --
Sandahl 2023 Overall 49 -- 28 (57.1) 20 (40.8) --
Tabbara 2024 Overall 25 1 (4.0) -- -- --
Tan 2023a Overall 204 2 (1)a -- 105/153 (69) --
Tan 2023b Overall 113 -- 41 (36.3) -- --
Tan 2024 Overall 86 2 (2) 35 (41) -- --
Notes: Double dashes (“—“) indicate data not reported. Table only includes studies where the relevant characteristics were reported. a) n hand calculated; b) Overall population was treated with prophylactic tocilizumab; c) Assumed based on inclusion criteria. Abbreviations: CrCl, creatine clearance; CNS, central nervous system; TCRT, T-cell redirection therapy; TCZ, tocilizumab; TEC, teclistamab.
Table E.3. Summary of key effectiveness outcomes.
Table E.3. Summary of key effectiveness outcomes.
Study ID Overall / subgroup details Sample size Timepoint / mFU Overall response rate, n (%) Stratified best response, n (%)
PR or better VGPR or better CR or better PD SD PR VGPR CR sCR
Asoori 2023 Overall 46 Median 3 months 32a (70.0) -- -- -- -- 7 (15.2)b 19 (41.3)b 6 (13.0)b
Dima 2023 Overall 104 Median 3.8 months 70 (66) -- -- 26 (24) 10 (9.5) 21 (20) 18 (17) 31 (29)
>70 years old 34 Median 3.8 months 24 (71) -- 10 (30)c -- -- -- -- -- --
Faiman 2023 Overall 26 Median 2.5 months -- -- -- 6 (24) 4 (16) 6 (24) 5 (20) 4 (16) --
Firestone 2023 Overall 47 Median 3.1 months 30 (64) 18a (38) -- -- -- -- -- -- --
Ghamsari 2024 Overall 18 June 2023 cut-off 9a (50) 9a (50) -- -- -- -- -- -- --
Gordon 2023 Overall 58 -- 29a (50.0) 14a (24.1) -- -- 8a (13.1)b 15a (25.9) 14a (24.1) -- --
Grajales-Cruz 2023 Overall 36 Median 4.2 months 19a (52.8) -- -- -- -- 3a (8.3) 0 (0.0) 16a (44.5)
Hebraud 2023 Overall 8 July 2023 cut-off -- 6 (75)b -- -- -- -- -- -- --
Kowalski 2023 Patients with secretory diseased 30 Median 3.4 monthse 15 (50) -- -- 4 (13) 11 (37) 4 (13) -- 9 (30) --
Kumar 2023 Overall 9 3 months 6 (66.7) -- -- 3 (33.3)b -- 2 (22.2)b 1 (11.1)b 1 (11.1)b 2 (22.2)b
Lachenal 2023 Overall 15 Median 5.2 months 13 (86.7)b -- -- -- -- 2 (13.3)b 7 (46.7)b 2 (13.3)b 2 (13.3)b
Midha 2023 Overall 56 Median 2.3 monthse 30a (53.6) -- -- -- -- -- -- -- --
Mohan 2024 Overall 98 Median 3.5 months 61 (62) 50a (51) 20a (20) -- -- -- -- -- --
Nader 2023 Overall 27 33.6 monthsf 19 (70) -- -- -- -- -- -- -- --
Riedhammer 2024 Overall 123 Median 5.5 months 73a (59.3) -- -- -- -- 14a (11.4) 32a (26.0) 27a (22.0)g
Schaefers 2023 Overall 16 3.4 monthse 7a (44) 5a (31) -- 7a (44) 2a (13) 2a (13) -- -- --
Tan 2023a Overall 180 Median 5 months 115a (64) -- -- 40a (22) 25a (14) 25a (14) 56a (31) 34a (19)
Tan 2024 Overall 86 Median 9.5 months 47 (61.0) 33 (43.0) -- -- -- -- -- -- --
Prior BCMA-directed therapy 32 Median 9.5 months 14 (43) -- -- -- -- -- -- -- --
Venkatesh 2023 Overall 22 Median 3.1 months 11a (50) -- -- -- -- -- -- --
Notes: Double dashes (“—“) indicate data not reported. Table only includes studies where the relevant outcomes were reported. a) n hand calculated; b) % hand calculated; c) Based on July 2023 cut-off (n=33); d) Population was treated with prophylactic tocilizumab; e) Converted from days to months; f) Converted from years to months; g) Reported as near complete or complete response. Abbreviations: BCMA, B-cell maturation antigen; CI, confidence interval; CR, complete response; NA, not available; NR, not reached; PD, progression of disease; PR, partial response; sCR, stringent complete response; SD, stable disease; TEC, teclistamab; VGPR, very good partial response.

Appendix F – Summary of Real-World Outcomes from Large, Multi-Center Chart Review Studies

Table F.1. Summary of real-world outcomes from large, multi-center chart review studies.
Table F.1. Summary of real-world outcomes from large, multi-center chart review studies.
MajestTEC-1
(n=165)		 Tan 2023a
(n=204)		 Dima 2023
(n=106)		 Mohan 2024
(n=110)		 Gordon 2023
(n=58)		 Riedhammer 2024
(n=123)
Study description
Study design Clinical trial Retrospective RW study Retrospective RW study Retrospective RW study Retrospective RW study Retrospective RW study
MajesTEC-1 ineligibilty, % 0 70 83 -- 87.9 39
Median follow-up, mos 23 5 3.8 3.5 -- 5.5
Median prior LOTs 5 6 6 6 5 6
Data source & setting -- 9 academic centers across 5 countries 5 US academic centers as part of UMIRC 5 US academic centers 4 academic centers in NYC metro area 18 German centers
Select efficacy/effectiveness
ORR, % (overall) 63 64 66a 62 50 59.3
CR or better, % 45.5 19 29 20 -- 22
VGPR or better, % 59.4 50b 46b 51 24.1 48b
Median PFS, mos (95% CI) 11.3 (8.8 – 16.4) 13 5.4 (3.4 – NR) 6-month rate: 52% (42% - 64%) 2.83 (1.18 – NA) 8.7
Median OS, mos (95% CI) 21.9 (15.1 – NE) 15 NR 6-month rate: 80% (72% - 89%) NR (4.27 – NA) NR
Select safety
CRS (any grade), % 72 Overall: 54c
Inpatient: 59
Outpatient: 36		 64 56 52 58.5
ICANS (any grade), % 3 -- 14 11 11 --
Infections (any grade), % 80 60 31 40b -- 54.5
Notes: Double dashes (“—“) indicate data not reported. a) Evaluable population n=104; b) Calculated from stratified best response; c) Calculated from stratified cohorts. Abbreviations: CR, complete response; CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; LOT, line of therapy; NA, not available; NE, not estimated; NR, not reached; NYC, New York City; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; RW, real-world; US, United States; USMIRC, U.S. Myeloma Innovations Research Collaborative.

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Figure 1. PRISMA flow diagram of included studies. Abbreviations: ASCO, American Society of Clinical Oncology; ASH, American Society for Hematology; EHA, European Hematology Association; HOPA, Hematology/Oncology Pharmacy Association; IMS, International Myeloma Society; LL&M, Lymphoma, Leukemia & Myeloma Congress; ONS, Oncology Nursing Society; SOHO, Society of Hematologic Oncology.
Figure 1. PRISMA flow diagram of included studies. Abbreviations: ASCO, American Society of Clinical Oncology; ASH, American Society for Hematology; EHA, European Hematology Association; HOPA, Hematology/Oncology Pharmacy Association; IMS, International Myeloma Society; LL&M, Lymphoma, Leukemia & Myeloma Congress; ONS, Oncology Nursing Society; SOHO, Society of Hematologic Oncology.
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Figure 2. Overlay of progression-free survival (a) and overall survival (b) curves reported up to 18 months in included studies. Values under the curves represent the number of patients at risk in each study. N at risk was generated based on reconstructed individual patient data for Asoori 2023, Dima 2023, Gordon 2023, Grajales-Cruz 2023, Midha 2023, Tan 2023a, and Schaefers 2023. The maximum PFS follow-up in Tan 2023a was 26.5 months.
Figure 2. Overlay of progression-free survival (a) and overall survival (b) curves reported up to 18 months in included studies. Values under the curves represent the number of patients at risk in each study. N at risk was generated based on reconstructed individual patient data for Asoori 2023, Dima 2023, Gordon 2023, Grajales-Cruz 2023, Midha 2023, Tan 2023a, and Schaefers 2023. The maximum PFS follow-up in Tan 2023a was 26.5 months.
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Table 1. Summary of study characteristics and outcomes evaluated.
Table 1. Summary of study characteristics and outcomes evaluated.
Study ID Study design Data source Chart review vs. secondary database Setting Study timeframe mFU (months) Sample size Relevant outcomes evaluated
Asoori 2023 [24] Retrospective Treated patients at UCSF Chart review Academic, single-center NR – July 2023 3 46 ORR, OS, PFS, Infection AEs, IVIG use in AEs
Banerjee 2023a [25] Retrospective All-payer claims database (ARMMRD) Secondary database Multi-center October 2022 – July 2023 -- 182 LOS, CRS
Banerjee 2023b [26,27] Retrospective Acentrus MM electronic medical records (EMRs) Secondary database Academic centers/ community-based hospitals, multi-center October 2022 – November 2023 5.1 247 LOS, CRS, ICANS, step-up dosing schedule, time to treatment switch or death
Bansal 2023 [28,29] Retrospective Treated patients at the Mayo Clinic, Rochester, MN Chart review Academic, single-center October 2020 – July 2023 -- 24 LOS, CRS, remote monitoring, hospitalizations
Bansal 2024 [30] Retrospective Treated patients at the Mayo Clinic Rochester, MN Chart review Academic, single-center December 2022 – January 2024 -- 48 ORR
Bolton 2024 [31] Prospective Treated patients at three Kaiser Permanente institutions Chart review Academic, multi-center NR -- 9 CRS, ICANS, discontinuations due to any cause
Catamero 2023 [32] Retrospective Treated patients at Mount Sinai Hospital Chart review Academic, single-center December 2022 – May 2023 -- 26 CRS, TCZ use in AE management
Charkviani 2024 [33] Retrospective Patients treated at the Mayo Clinic Healthcare System Chart review Academic, multi-center December 2022 – May 2023 -- 34 Acute kidney injury (AKI) incidence and treatment
Dima 2023 [12,34,35,36,37] Retrospective Treated patients at USMIRC centers Chart review Academic, multi-center August 2022 – August 2023 3.8 106 CRS, ICANS, Infections, ORR, DOR, OS, PFS, TCZ use in AE management, hospitalizations
Faiman 2023 [38] Retrospective Treated patients at Cleveland Clinical Chart review Academic, single-center December 2022 – May 2023 2.5 26 CRS, TCZ use in AE management, ICANS, infections, best response
Firestone 2023 [17,39,40,41] Retrospective Treated patients at Memorial Sloan Kettering Cancer Center Chart review Academic, single-center November 2022 – July 2023 3.1 52 Survival, PFS, ORR, safety
Ghamsari 2024 [42] Retrospective Treated patients at University of California San Diego Chart review Academic, single-center January 2023 – June 2023 -- 18 CRS, ICANS, Infections, ORR, DOR, OS, PFS, TCZ use in AE management
Glenn 2024 [43] Prospective Treated patients at Smilow Cancer Hospital at Yale New Haven Hospital Chart review Academic, single-center NR -- 18 CRS
Gong 2023 [21] Retrospective FDA Adverse Event Reporting System database Secondary database Multi-center 2019 – 2023 -- 719a Reporting OR, CRS, ICANS, infection, non-ICANS neurotoxicity, mortality, hospitalizations
Gordon 2023 [44] Retrospective Treated patients at four New York City metro area centers Chart review Academic, multi-center NR -- 58 ORR, CRS, ICANS, Tocilizumab use in AE management, discontinuations
Graf 2024 [45] Retrospective Treated patients at Medical University of South Carolina Chart review Academic, single-center November 2022 – August 2023 -- 25 Hospitalization, LOS, proportion of fever at each dose of teclistamab;, incidence, severity, and onset of CRS
Grajales-Cruz 2023 [46,47] Retrospective Treated patients at Lee Moffitt Cancer Center; chart review Chart review Academic, single-center December 2022 – October 2023 4.2 36 ORR, PFS, OS, CRS, TCZ use in AE management, infection, LOS, ICU admission
Hamadeh 2024 [18,48,49] Retrospective Memorial Sloan Kettering Cancer Center’s institutional plasma cell disorders database Chart review Academic, single-center November 2022 – July 2023 -- 69 CRS
Hebraud 2023 [50] Retrospective Treated patients at Institut Universitaire du Cancer de Toulouse Chart review Academic, single-center January 2021 – July 2023 -- 8 CRS, ORR, TCZ & IVIG use in AE management
Howard 2023 [51] Retrospective Treated patients at the Memorial Sloan Kettering Cancer Center Chart review Academic, single-center NR -- 23 LOS, unscheduled physician communications, hospitalizations
Kawasaki 2024 [52] Retrospective Treated patients at the University of California Davis (UCD) medical center Chart review Academic, single-center December 2022 – December 2023 -- 27 CRS, ICANS, LOS, hematological toxicities, infections, hepatotoxicity, diarrhea, and IVIG in AE management
Kowalski 2023 [53] Prospective Treated patients at University of Miami Hospital & Clinics, Sylvester Comprehensive Cancer Center Chart review Academic, single-center October 2022 – July 2023 3.4b 31 Best response, ORR, CRS, ICANS, PFS
Kumar 2023 [54] Prospective Treated patients at University of Connecticut Health Center Chart review Academic, single-center November 2022 – February 2023 -- 9 Best response, ORR, CRS, ICANS
Lachenal 2023 [55] Retrospective Treated patients in French AP program Secondary databasec Multi-center November 2022 – October 2023 5.2 15 CRS, TCZ use in AE management, ICANS, ORR, IVIG in AE management
Marin 2023 [56] Prospective Treated patients at Emory University hospital Chart review Academic, single-center December 2022 – August 2023 -- 53 CRS, TCZ use in AE management, TCZ dosing, ICANS, readmissions,
Midha 2023 [22] Retrospective Treated patients at Dana-Farber Cancer Institute/Brigham and Women’s Hospital Chart review Academic, single-center NR – August 2023 2.3b 56 CRS, TCZ use in AE management, infections, ORR, PFS
Mohan 2024 [19,57] Retrospective Treated patients at 5 US academic centers Chart review Academic, multi-center NR 3.5 110 CRS, ICANS, Infections, ORR, best response, LOS, IVIG use in AE management, TCZ use in AE management
Mooney 2024 [58] Retrospective Patients treated at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital Chart review Academic, single-center January 2023 – NR -- 19 Hospital admission, LOS, CRS and ICANS
Nader 2023 [23] Retrospective Patients treated at the Indiana University School of Medicined Chart review Academic, single-centerd 2000 – 2021e 33.6f 49 PFS, OS, treatment response
Perrot 2023 [59] Retrospective Treated patients in French AP program Secondary databasec Multi-center October 2022 – April 2023 2.9 572 Discontinuations, AE-related mortality
Pianko 2024 [60] Retrospective Komodo Healthcare MapTM Secondary database Multi-center October 2022 – December 2023 4.2 419 Dosing schedule of teclistamab, time to less frequent dosing, time to next treatment (TTNT)
Rees 2024 [61] Retrospective Treated patients at the Mayo Clinic centers Chart review Academic, multi-center April 2018 – June 2023 9 41 PFS, DOR, OS
Riedhammer 2024 [20,62] Retrospective Treated patients at 18 German centers Chart review Multi-center July 2022 – October 2023 5.5 123 Time to response, best response, ORR, PFS, infections
Sandahl 2023 [7,63] Retrospective Treated patients at 3 Mayo Clinic centers Chart review Academic, multi-center October 2022 – September 2023 -- 49 CRS, ICANS, TCZ use in AE management, admissions, LOS, time between TEC administration & check-out
Schaefers 2023 [64] Prospective Treated Patients at the University Medical Center Hamburg-Eppendorf tertiary center Chart review Academic, single-center July 2022 – May 2023 3.4b 16 CRS, ICANS, infections, neutropenia, ORR, OS, PFS, DOR
Tabbara 2024 [65] Retrospective Treated patients at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center; Inpatient/Outpatient unit Chart review Academic, single-center January 2023 – December 2023 -- 25 Neutropenia, infection, CRS, ICANS, patients receiving dexamethasone, hospital admission, death
Tan 2023a [66,67,68] Retrospective Treated patients at IMF-associated centers Chart review Academic, multi-center NR – October 2023 5 204 ORR, OS, PFS, CRS, ICANS, TCZ use in AE management, IVIG use in AE management, LOS
Tan 2023b [69,70] Retrospective Premier healthcare database Secondary database Multi-center November 2022 – March 2023 -- 113 LOS, step-up dosing schedule, hospitalizations, CRS, TCZ use in AEs
Tan 2024 [71,72] Retrospective Treated patients at the Memorial Sloan Kettering Cancer Center Chart review Academic, single-center November 2022 – March 2024 Overall population: 9.5
Patients switching to less-frequent dosing:
6.4		 86 ORR, DOR, PFS, time to response
Varshavsky-Yanovsky 2023 [9,73] Retrospective Treated patients at Fox Chase Cancer Center Chart review Academic, single-center December 2022 – May 2023 -- 18 CRS, ICANS
Venkatesh 2023 [74] Retrospective Treated patients at the University of Kansas Chart review Academic, single-center NR – February 2023 3.1 22 CRS, ICANS, ORR, mortality, best response
Notes: a) Number of adverse event cases; note this differs from other studies which report number of individual patients and therefore not included in result summary; b) Converted from days to months; c) French AP program follows hospitals that request reimbursement for innovative medicines prior to and after market authorization, data comes from these reimbursement claims; d) Not reported; assumed based on all but one authors’ affiliation being the Indiana University School of Medicine; e) Given the FDA approval of TEC in 2022, the year 2000 start date is assumed to be an error; f) Converted from years to months. Abbreviations: AE, adverse event; AKI, acute kidney injury; AP, Accès Précoce; ARMMRD, All-payer Real-world Multiple Myeloma Research-ready Data; CRS, cytokine release syndrome; DOR, duration of response; EMR, electronic medical record; FDA, Food and Drug Administration; ICANS, Immune effector cell-associated neurotoxicity syndrome; ICU, intense care unit; IMF, International Myeloma Foundation; IVIG, intravenous immunoglobulin; LOS, length of stay; mFU, median follow-up; MM, multiple myeloma; MN, Minnesota; NR, not recorded; PFS, progression-free survival; ORR, overall response rate; OS, overall survival; TCZ, tocilizumab; TEC, teclistamab; TTNT, time to next treatment; UCD, University of California Davis; UCSF, University of California San Francisco; US, United States; USMIRC, US Myeloma Innovations Research Collaborative.
Table 2. Summary of patient characteristics.
Table 2. Summary of patient characteristics.
Study ID Overall / subgroup details Sample size Median age (range), years Female, n (%) Race, n (%) High risk cytogenetics, n (%) Median prior lines of therapy Extramedullary disease, n (%)
White Black Asian
Asoori 2023 Overall 46 71 (50 – 91) 23 (50.0)a 23 (50.0) 2 (4.3) 14 (30.4) 13 (38.2) 7 --
Banerjee 2023a Overall 182 73 (39 – 85) 91 (50.0) 123 (67.6) 20 (11.0) 5 (2.7) -- -- --
Banerjee 2023b Overall 247 69 (41 – 89) 111 (44.9) 138 (75.8)b 23 (12.6)b 21 (11.5)b -- -- 14 (5.7)
Bansal 2023 Overall 24 66 9 (39)a -- -- -- 9 (38) 5 --
Bansal 2024 TEC treatment groupc 48 -- -- -- -- -- -- -- --
Bolton 2024 Overall 9 -- -- -- -- -- -- -- --
Catamero 2023 Overall 26 -- -- -- -- -- -- -- --
Charkviani 2024 TEC treatment group 34 66.4 (55.4 – 70.8)d 11 (32.4) 31 (91.2) 1 (2.9) 1 (2.9) -- -- --
Dima 2023 Overall 106 66.5 (35 – 87) 55 (54)a 72 (68) 28 (26) 2 (2) 56 (59) 6 45 (42)
>70 years old 33 75 (71 – 87) -- -- -- -- 19 (58) 6 13 (39)
Patients with EMD 45 68 (43 – 83) 10 (22.0)a 35 (78.0) -- -- 25 (55.5) 6 45 (100.0)
Faiman 2023 Overall 26 64 (45 – 75) 14e (54) 19e (73) -- -- -- 7 --
Firestone 2023 Overall 52 70 (30 – 80) -- -- -- -- 17 (33) 7 18 (35)
Ghamsari 2024 Overall 18 67 (50 – 83) -- -- -- -- 11 (84.6)f,g 6.5 8 (44)
Glenn 2024 Overall 18 -- -- -- -- -- -- -- --
Gong 2023 Overall 719 casesh 65 (57 – 72)e 229 (31.8) -- -- -- -- -- --
Gordon 2023 Overall 58 67 (45 – 88) 31 (53.4) 26 (45.6) 15 (26.3) 3 (5.2) 21 (36.2) 5 28 (48.3)
Graf 2024 Overall 25 66 (37 – 78) 12 (48.0) 14 (56.0) -- -- 9 (36.0) 5 13 (52.0)
Grajales-Cruz 2023 Overall 36 67 (48 – 88) 16 (44.4)a -- -- -- 15 (44.1) 7 16 (57.0)
Hamadeh 2024 Overall 72 (39 – 88) 30 (41.7)i 56 (77.8)i 12 (16.7)i -- 36 (50.0)i -- 21 (29.2)i
Prior T-cell redirection therapies (TCRT) 27 70 (51 – 88) 10 (37) 23 (85) 2 (7) -- 19 (70) 8 9 (33)
No prior TCRT 45 69 (39 – 88) 20 (44) 33 (73) 10 (22) -- 17 (38) 5 12 (27)
Hebraud 2023 Overall 8 69 (43 – 81) -- -- -- -- -- 4 --
Howard 2023 Overall 23 67 (51 – 88) -- -- -- -- 5 (22) 6 6 (26)
Kawasaki 2024 Overall 27 -- 12 (44.4)i 18 (66.7)i -- -- -- -- 8 (29.6)i
Dosing schedule 1, 3, 5 (days) 23 69 9 (39)f 16 (69) -- -- -- -- 6 (26)
Dosing schedule 1, 4, 7 (days) 4 64 3 (75)f 2 (50) -- -- -- -- 2 (50)
Kowalski 2023 Overallj 31 71 (50 – 84) 21 (68) 22 (71) -- -- 9 (29) 5 24 (77)
Kumar 2023 Overall 9 75 (41 – 81) -- -- -- -- -- 6 --
Lachenal 2023 Overall 15 68 (58 – 83) -- -- -- -- 7 (70.0)k 4 --
Marin 2023 Overall 53 69 (43 – 83) 15 (28.3)a,i 25 (47.2)i 24 (45.3)i 1 (1.9)i 21 (39.6)i -- --
No prophylactic tocilizumab (TCZ) 15 58 (47 – 73) 2 (13.3)a 7 (46.7) 8 (53.3) -- 4 (26.7) 6 --
Prophylactic TCZ 38 69 (43 – 83) 13 (34.2)a 18 (47.4) 16 (42.1) 1 (2.6) 17 (44.7) 5 --
Midha 2023 Overall 56 69 (45 – 83) 21 (37.5)a -- -- -- -- 6 24 (42.9)
Mohan 2024 Overall 110 68 (37 – 89) 54 (49) 67 (61) 32 (29) 2 (1.8) 59l (62) 6 48 (44)
Mooney 2024 Overall 19 -- -- -- -- -- -- -- --
Nader 2023 Overall 49 70 (59 – 75)d 27 (55.0) 41 (84.0) 5 (10.0) -- -- >4 --
Perrot 2023 Overall 572 71 (64 – 76)d 241 (42.1) -- -- -- 124 (21.7) 4 121 (21.2)
Pianko 2024 Overall 419 65 (58 – 73)d 183 (43.7) 185 (63.4)m 91 (31.2)m 16 (5.4)m -- 5 --
Rees 2024 TEC treatment groupc 41 -- -- -- -- -- -- -- --
Riedhammer 2024 Overall 123 67 (35 – 87) 53e (43.1) -- -- -- 39 (36.8)n 6 43 (36.1)
Sandahl 2023 Overall 49 67.2 (38.7 – 84.2) 18 (36.7) 43 (87.8) 3 (6.1) 1 (2.0) 31 (63.3) -- 3 (6.1)
Schaefers 2023 Overall 16 65.5 (51 – 86) 5 (31) -- -- -- 8 (80) 6 --
Tabbara 2024 Overall 25 70 (59 – 89) 14 (56.0) 19 (76.0) 5 (20.0) 0 (0.0) -- 6 --
Tan 2023a Overall 204 66 (33 – 91) 91 (45) 143 (70) 15 (7) 19 (9) 90 (44) 6 38 (19)
Tan 2023b Overall 113 65 (58 – 74)d 44 (38.9) 74 (65.5) 24 (21.2) 3 (2.7) -- -- --
Tan 2024 Overall 86 71 (64 – 78)d 44 (51) 65 (76) 14 (16) -- 56 (71)o 6 30 (38)o
Patients switched to less frequent dosing schedule 32 70 (65 – 78)d 20 (62)a -- 3e (9) -- 17 (59) 6 10 (34)p
Varshavsky-Yanovsky 2023 Overall 18 66 (46 – 81) -- -- -- -- -- -- --
Venkatesh 2023 Overall 22 70 (43 – 85) 9 (41)g -- -- -- 9 (41) 6 14 (64)
Notes: Double dashes (“—“) indicate data not reported. a) Calculated from reported proportion of males; b) Evaluated population = 186; c) Overall population combined multiple treatments, TEC only data is limited; d) IQR; e) n hand calculated; f) Evaluable population n=13; g) % hand calculated; h) Number of individual cases; i) Calculated from stratified cohorts; j) Overall population was treated with prophylactic tocilizumab; k) n=10 evaluable; l) n=95 evaluable; m) Evaluable population n=292; n) Evaluable population n=106; o) Evaluable population n=79; p) Evaluable population n=29. Abbreviations: EMD, extramedullary disease; IQR, interquartile range; TCRT, T-cell redirection therapies; TCZ, tocilizumab; TEC, teclistamab.
Table 3. Summary of MajesTEC-1 ineligibility.
Table 3. Summary of MajesTEC-1 ineligibility.
Study ID Overall / subgroup details Sample size MajesTEC-1 ineligibility, n (%) Prior BCMA therapy, n (%) ECOG PS ≥2, n (%) Cytopenia, n (%) Renal impairment/ failure, n (%) CrCl <30mL/min or 40mL/min, n (%)
Overall Anemia Neutropenia Thrombocytopenia
Asoori 2023 Overall 46 31 (67.3) 16 (34.8) -- -- -- -- -- -- 15 (32.6)
Banerjee 2023a Overall 182 -- 15 (16.3)a -- -- 108 (59.3) 36 (19.8) -- 77 (42.3) --
Banerjee 2023b Overall 247 -- 48 (19.4) -- -- 126 (51.0) 55 (22.3) -- 100 (40.5) --
Dima 2023 Overall 106 88 (83) 56 (53) 35 (33) 33 (31) 27 (25) 2 (2) 21 (20) 14 (13) 14 (13)
>70 years old 33 -- -- 15 (45.0 -- -- -- -- -- --
Patients with EMD 45 -- 25 (55.5) 16 (35.5) -- -- -- -- -- --
Faiman 2023 Overall 26 -- 9 (38) -- -- -- -- -- -- --
Firestone 2023 Overall 52 -- 27 (52) -- -- -- -- -- -- --
Ghamsari 2024 Overall 18 -- 7 (39) -- -- -- -- -- -- --
Gordon 2023 Overall 58 51 (87.9) 23 (39.7) 17 (29.8) (48.3) -- -- -- 13 (22.4) --
Graf 2024 Overall 25 -- 11 (44) -- -- -- -- -- -- --
Grajales-Cruz 2023 Overall 36 36 (100.0) 36 (100.0) -- -- 7 (22.6) 2 (6.45) 10 (32.3) -- 6 (18.8)
Howard 2023 Overall 23 -- 8 (35) -- -- -- -- -- -- --
Kowalski 2023 Overallc 31 26 (84) 4 (13) 16 (52)d 15 (48)e -- -- -- -- --
Lachenal 2023 Overall 15 -- -- -- -- -- -- -- 15 (100)f --
Midha 2023 Overall 56 45 (80.0) 20 (35.7) 17 (30.4) -- -- -- -- -- 11 (19.6)
Mohan 2024 Overall 110 -- 38 (35) -- -- -- -- -- -- --
Perrot 2023 Overall 572 -- 49g (8.6) 108g (18.9)d -- -- -- -- 102g (17.8) --
Pianko 2024 Overall 419 -- 102 (24.3) -- -- 164 (39.1) 50 (11.9) -- 206 (49.2) --
Rees 2024 TEC treatment groupb 41 -- 25 (61.0) -- -- -- -- -- -- --
Riedhammer 2024 Overall 123 48g (39) 45 (37.4) -- -- -- -- -- -- --
Sandahl 2023 Overall 49 -- 17 (34.7) -- -- 27 (55.1) 14 (28.6) -- 15 (30.6) --
Tan 2023a Overall 204 122 (70)h 91 (45.0) -- -- -- -- -- -- 25 (12)
Tan 2023b Overall 113 -- -- -- -- 65 (57.5) -- -- 32 (28.3) --
Tan 2024 Overall 86 -- 32 (37) 5 (10)i -- -- -- -- -- 9 (10)
Patients switched to less frequent dosing schedule 32 -- 10 (31) -- -- -- -- -- -- --
Notes: Double dashes (“—“) indicate data not reported. a) Based on evaluated population (n=92); b) Overall population combined multiple treatments, TEC only data is limited; c) Overall population was treated with prophylactic tocilizumab; d) % hand calculated; e) Reported as hematological ineligibility; f) Reported as renal disease; g) n hand calculated; h) Based on evaluated population (n=175); i) Based on evaluable population n=50. Abbreviations: BCMA, B-cell maturation antigen; CrCl, creatinine clearance; ECOG, Eastern Cooperative oncology Group performance status; EMD, extramedullary disease; TCRT, T-cell redirection therapy; TCZ, tocilizumab, TEC, teclistamab.
Table 4. Summary of key effectiveness outcomes.
Table 4. Summary of key effectiveness outcomes.
Study ID Overall / subgroup details Sample size Timepoint / mFU Overall response rate, n (%)
PR or better VGPR or better CR or better
Asoori 2023 Overall 46 Median 3 months 32b (70.0) 25 (54.3)c,d 6 (13.0)c,d
Bansal 2024 TEC treatment groupa 48 January 2024 cut-off 29b (61.0) -- --
Dima 2023 Overall 104 Median 3.8 months 70 (66)b 49 (46)c 31 (29)c
>70 years old 34 Median 3.8 monthse 24 (71) -- 10 (30)f
Faiman 2023 Overall 26 Median 2.5 months 15 (60)c 9 (36)c 4 (16)c
Firestone 2023 Overall 47 Median 3.1 months 30 (64) 18b (38) --
Prior anti-BCMA exposure 26 Median 3.1 monthse 13 (50.0) -- --
Ghamsari 2024 Overall 18 June 2023 cut-off 9b (50) 9b (50) --
Gordon 2023 Overall 58 -- 29b (50.0) 14b (24.1) --
Grajales-Cruz 2023 Overall 36 Median 4.2 months 19b (52.8) 16b (44.5)c 16b (44.5)c
Hebraud 2023 Overall 8 July 2023 cut-off -- 6 (75)d --
Kowalski 2023 Patients with secretory diseaseg 30 Median 3.4 monthsh 15 (50) -- 9 (30)c
Kumar 2023 Overall 9 3-month evaluation 6 (66.7) 4 (44.4)c 3 (33.3)c
Lachenal 2023 Overall 15 Median 5.2 months 13 (86.7)d 11 (73.3)c,e 4 (26.7)c,d
Midha 2023 Overall 56 Median 2.3 monthsh 30b (53.6) -- --
Mohan 2024 Overall 98 Median 3.5 months 61 (62) 50b (51) 20b (20)
Nader 2023 Overall 27 Median 33.6 monthsi 19 (70) -- --
Riedhammer 2024 Overall 123 Median 5.5 months 73b (59.3) 59b (48.0)c 27b (22.0)c,j
Schaefers 2023 Overall 16 Median 3.4 monthsh 7b (44) 5b (31) --
Tan 2023a Overall 180 Median 5 months 115b (64) 90b (50)c 34b (19)c
Tan 2024 Overall 77 Median 9.5 months 47 (61) 33 (43) --
Prior BCMA-directed therapy 32 Median 9.5 monthse 14 (43) -- --
Venkatesh 2023 Overall 22 Median 3.1 months 11b (50) -- --
Notes: Double dashes (“—“) indicate data not reported. a) Overall population studied TEC and other interventions in a combined cohort, the stratified subgroup data is presented here and is included in overall ranges; b) n hand calculated; c) Calculated from stratified best response; d) Based on July 2023 cut-off (n=33); e) Median follow-up assumed to apply to subgroup data as both share the same data cut-off; f) % hand calculated; g) Population was treated with prophylactic tocilizumab; h) Converted from days to months; i) Converted from years to months; j) Reported as near complete or complete response. Abbreviations: BCMA, B-cell maturation antigen; CR, complete response; mFU, median follow-up; PR, partial response; TEC, teclistamab; VGPR, very good partial response.
Table 5. Summary of key safety outcomes.
Table 5. Summary of key safety outcomes.
Study ID Overall / subgroup details Sample size Timepoint / mFU CRS, n (%) ICANS, n (%) Infections, n (%)
Any grade Grade 1 Grade 2 Grade 3+ Any grade Grade 1 Grade 2 Grade 3+ Any grade Grade 3+
Chart review – mixed inpatients and outpatient, or not reported
Asoori 2023 Overall 46 Median 3 months -- -- -- -- -- -- -- -- 39 (84.8) 14 (35.8)a
Bansal 2023 Overallb 24 July 2023 cut-off 13 (54.2) -- -- -- -- -- -- -- -- --
Catamero 2023 Overall 26 May 2023 cut-off 20c (78) -- -- -- -- -- -- -- -- --
CRS patients 20 May 2023 cut-off -- 17c (85) 3c (15) 0 (0) -- -- -- -- -- --
Glenn 2024 Overall 18 -- 1 (5.6) -- -- -- -- -- -- -- -- --
Gordon 2023 Overall 58 -- 30c (52) -- -- -- 6c (11) -- -- -- -- --
Grajales-Cruz 2023 Overall 36 Median 4.2 months 21 (58.3) 15 (45.5) 4 (12.1) 0 (0) -- -- -- -- 21 (58.3) --
Hamadeh 2024 Overall 72 July 2023 cut-off 46c (63.9)d 36c (50.0)d 10c (13.9)d -- -- -- -- -- -- --
Prior TCRT 27 July 2023 cut-off 10c (37) 8c (30) 2c (7) -- -- -- -- -- -- --
No prior TCRT 45 July 2023 cut-off 36c (80) 28c (62) 8c (18) -- -- -- -- -- -- --
Kawasaki 2024 Overall 27 -- -- 13c (48.1)d,e -- 4c (14.8)d -- -- -- -- --
Dosing schedule 1, 3, 5 (days) 23 -- -- 11 (48)e -- 4 (17) -- -- -- -- --
Dosing schedule 1, 4, 7 (days) 4 -- -- 2 (50)e -- 0 (0) -- -- -- -- --
Kowalski 2023 Prophylactic tocilizumab 31 Median 3.4 monthsf 4c (13) -- -- -- 3c (10) -- -- -- 8 (26) --
Kumar 2023 Overall 9 3-month evaluation 7 (77.8)d -- -- -- 1 (11.1)d -- -- -- -- --
Midha 2023 Overall 56 Median 2.3 monthsf 29 (51.8) -- -- 1 (1.8) -- -- -- -- 32 (57.1) --
Mohan 2024 Overall 110 Median 3.5 months 62c (56) 57c (51.8)d,e 5 (4.5)d 12 (11) -- -- 5 (4.5) 44 (40) 29 (26)
Riedhammer 2024 Overall 123 Median 5.5 months 72 (58.5) -- -- 2 (1.6) -- -- -- -- 67 (54.5) 33 (26.8)
Tabbara 2024 Overall 25 December 2023 cut-off -- 15 (60)e 0 (0) 4 (16) -- 2 (8) 0 (0) 6 (24) 3 (12)
Tan 2023a Overall 204 Median 5 months 110 (53.9)c,d 84 (41.2)c,d 25 (12.3)c,d 1 (0.5)c,d -- -- -- -- 115 (60.0) --
Venkatesh 2023 Overall 22 Median 3.1 months -- 9 (41.0)d,e -- 5 (23) -- -- 2 (9) -- --
Chart Review – inpatient monitoring
Bolton 2024 Overall 9 -- -- 3 (33.3) -- -- -- 2 (22.2) -- -- -- --
Dima 2023 Overall 106 Median 3.8 months 68 (64) 57 (54) 10 (9) 1 (1) 15 (14) 5 (5) 7 (6) 3 (3) 33 (31) --
>70 years old 33 July 2023 cut-off 22 (67) -- -- 1 (3) 7 (21) -- -- 0 (0) 11 (33) --
Faiman 2023 Overall 26 Median 2.5 months 22 (85) -- -- -- 5 (19) -- -- -- 7 (26.9)e --
Firestone 2023 Overall 52 Median 3.1 months 27 (52) -- -- -- -- -- -- -- -- --
Ghamsari 2024 Overall 18 June 2023 cut-off 12 (67) -- 4 (22.2)d 0 (0) 2 (11) -- 1 (5.6)d -- 12c (67) --
Graf 2024 Overall 25 August 2023 cut-off 13 (52) 12 (48) 1 (4) -- 1 (4) -- -- -- -- --
Marin 2023 Overall 53 August 2023 cut-off 21c (39.6)g -- -- -- 5 (9.4)c -- -- -- -- --
Prophylactic TCZ 38 August 2023 cut-off 10c (26.3) -- -- -- 2c (5.3) -- -- -- -- --
No prophylactic TCZ 15 August 2023 cut-off 11c (73.3) -- -- -- 3c (20.0) -- -- -- -- --
Mooney 2024 Patients admitted to hospital 15 -- 13 (86.7)d,h -- -- -- 13 (86.7)d,h -- -- -- -- --
Schaefers 2023 Overall 16 Median 3.4 monthsf 4 (25) -- -- 0 (0) 0 (0) -- -- 0 (0) 13 (81) 9 (56)
Tan 2023a Inpatients 160 Median 5 months 94 (59) 72 (45) 22 (14) 0 (0) -- -- -- -- -- --
Chart review – outpatient monitoring
Hebraud 2023 Overall 8 July 2023 cut-off 3 (37.5)d -- -- -- -- -- -- -- -- --
Sandahl 2023 Overall 45 September 2023 cut-off 13 (28.9) 10 (22.2) 2 (4.4) 1 (2.2) 2 (4.4) -- -- -- -- --
Tan 2023a Outpatients 44 Median 5 months 16 (36) 12 (27) 3 (7) 1 (2) -- -- -- -- -- --
Varshavsky-Yanovsky 2023 Overall 18 6-month evaluation -- 5 (27.8) 1 (5.6) -- -- -- -- -- -- --
Secondary databases
Banerjee 2023a Overall 131 July 2023 cut-off 54 (41.2) 39 (29.8) 9 (6.9) 2 (1.5) -- -- -- -- -- --
Banerjee 2023b Overall 76 Median 5.1 months 14 (18.4) 8 (10.5) 3 (3.9) 1 (1.3) 3 (3.9) 2 (2.6) 1 (1.3) 0 (0) -- --
Gong 2023 Total count of AEs 1,317 eventsi -- 130 (9.5) events -- -- -- 34 (2.5) events -- -- -- 214 (15.7) events --
Lachenal 2023 Overall 15 Median 5.2 months -- 11 (73.3)d,e -- 1 (6.7)d -- -- -- 9 (60.0)d --
Tan 2023b Overall 58 April 2023 cut-off 15 (25.9) 11 (19.0) 4 (6.9) -- -- -- -- -- -- --
Notes: Double dashes (“—“) indicate data not reported. Results based on most recent timepoint in each study. A) Reported as grade ¾ infections; b) Most recent data cut-off no longer reports TEC alone and is not included in the overall population summary ranges; c) n hand calculated; d) % hand calculated; e) Reported as grade 1 and 2; f) Converted from days to months; g) Only the no tocilizumab cohort of the overall population is included in the ranges; h) Reported as CRS and/or ICANS; i) Total number of events, note this differs from other studies which report total number of patients. Abbreviations: AE, adverse event; CRS, cytokine release syndrome; ICANS, Immune effector cell-associated neurotoxicity syndrome; TCRT, T-cell redirection therapies; TCZ, tocilizumab.3.3.3. Healthcare provider practices and resource utilization.
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