Real-World Safety and Efficacy of Teclistamab for Patients with Heavily Pretreated Relapsed-Refractory Multiple Myeloma

Background: Teclistamab is a B-cell maturation antigen (BCMA) targeting bispecific T-cell engager approved in October of 2022 for patients with relapsed-refractory multiple myeloma (RRMM) who have received at least 4 prior lines of therapy (LOT) based on the results of the pivotal MajesTEC-1 trial. In this multicenter retrospective study, we evaluated the real-world safety and efficacy of teclistamab, highlighting patterns of utilization and outcomes, including patients who would have been considered ineligible for MajesTEC-1 trial.

Methods: Five U.S. academic centers, part of the US Myeloma Innovations Research Collaborative (USMIRC), contributed data to this retrospective analysis, which included 102 patients with RRMM who received teclistamab as of 7/1/2023. Baseline characteristics were outlined by descriptive analysis. Teclistamab was administered in a step-up dosing manner as per the package insert. All patients had received at least the two step up doses and the first full dose of teclistamab. Patients received antimicrobial prophylaxis, supportive care, and toxicity management per institutional protocols. Responses to therapy including overall response rate (ORR), very good partial response (VGPR), and complete response or better (≥CR) were evaluated using the International Myeloma Working group (IMWG) criteria. Adverse events were graded based on the CTCAE v5.0 criteria. The Kaplan-Meier method was used for progression free survival (PFS), duration of response (DOR), and overall survival (OS) calculation.

Results: Of the 102 patients included in this analysis, 25% were non-Hispanic Black and 44% had extramedullary disease (EMD); the median number of prior LOT was 6 (range 4-17). More than 80% (83/102) of the patients would not have met the MajesTEC-1 eligibility criteria; main reasons for ineligibility included: prior BCMA-directed therapy (BDT) (55%), ECOG performance status ≥2 (28%), and baseline cytopenias: grade 3-4 anemia (26%), and grade 3-4 thrombocytopenia (20%). All patients were triple class exposed and 92% were triple class refractory, 78% were penta-class exposed and 67% were penta-class refractory. More than half of the patients (55%) were refractory to prior BDT. Baseline characteristics are summarized in Table 1. Cytokine release syndrome (CRS) was observed in 65% of patients, all of which, except one, were grade 1-2 events, while immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 15% of the patients, with three patients having grade 3-4 events. The most common grade 3-4 hematological toxicities were neutropenia (23%), leukopenia (18%), thrombocytopenia (17%), and anemia (17%). Infections occurred in 28% of the patients, half of which were characterized as severe. The vast majority (80%) of infections involved the respiratory tract and 7% of patients discontinued teclistamab permanently due to recurrent or severe infections. After a median follow up of 3.2 months, the ORR was 64% for the entire cohort; ORR was 57%, 66% and 45% for patients who were BDT-refractory, penta-refractory, or had EMD, respectively. Of those who did respond, responses were found to be deep (72% ≥VGPR; 45% ≥CR). Patients that would have been ineligible for the MajesTEC-1 trial had an ORR of 59%. Detailed responses for the groups of interest are reported separately in Table 1. The estimated 6-month PFS, DOR, and OS of the entire cohort were 38% (95% CI, 26-56), 54% (95% CI, 34-85) and 68% (95% CI, 58-80), respectively (Figure 1). No treatment-related mortality was observed, although 26% of the patients had died at the time of data cut-off, with 89% of the deaths attributed to disease progression.

Conclusion: This is the largest real-world experience of the safety and efficacy of teclistamab for RRMM. Overall, teclistamab was well tolerated with no major safety concerns, despite worse performance status and cytopenias than the MajestTEC-1 trial population. Moreover, despite the increased incidence of high-risk features, including penta-refractoriness, BDT refractoriness, and presence of EMD in this heavily pre-treated RRMM patient population, early efficacy assessment of teclistamab in a real-world setting was encouraging.