Real-World Characteristics, Step-up Dosing Patterns, and Early Safety Outcomes of Patients with Multiple Myeloma Treated with Teclistamab within Vs. after the First Year of FDA Approval

Background The first-in-class B-cell maturation antigen (BCMA) x CD3 bispecific antibody, teclistamab, gained US regulatory approval in October 2022 for relapsed/refractory multiple myeloma (RRMM). Published real-world analyses of teclistamab in the US have used data cutoffs within one year of approval.1,2 We sought to examine real-world data of patients with RRMM who initiated teclistamab early (within one year of approval) vs later (after one year) to examine changes in patient characteristics, step-up dosing (SUD) patterns, or early safety outcomes as teclistamab is administered to more patients at more centers. Methods This was a retrospective observational cohort study using the All-payer Real-world Multiple Myeloma Research-ready Data (ARMMRD) registry, employing previously described methods and with an updated identification period between 10/26/22 and 1/31/24.3 Patients were classified as having a complete SUD period using a claims-based algorithm and stratified by index date into early initiators (October 2022 through September 2023) and recent initiators (September 2023 to January 2024). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were identified via ICD-10-CM codes and symptom-based codes (‘Keating algorithm‘4 for CRS) in patients with a complete SUD period. Variables were summarized descriptively. Results Among 754 patients who met study criteria, 506 (67%) were early initiators and 248 (33%) were recent initiators. Early initiators were younger than recent initiators (median age [range]: 70 years [31-84] vs 72 years [42-85]), with a higher proportion being <65 years (31% vs 21%). A higher proportion of early initiators than recent initiators had commercial insurance (16% vs 11%). In both cohorts, about half of the patients were male and most were White and non-Hispanic; Black or Asian race was reported in 18% of patients in both cohorts. Compared to recent initiators, early initiators had a higher mean (standard deviation) Quan-Charlson Comorbidity Index (QCCI) score (4.2 [3.9] vs 3.8 [3.7]) and numerically higher prevalence of baseline comorbidities such as peripheral neuropathy (39% vs 36%), hypogammaglobulinemia (29% vs 23%), and neutropenia (21% vs 15%). Prior to teclistamab, higher proportions of early initiators than recent initiators received commercial BCMA-targeted therapy (18% vs 10%) or stem cell transplant (SCT, 45% vs 36%). Among patients with an observed complete SUD by data cutoff (269 early and 115 recent initiators), higher proportions of recent initiators than early initiators had >1 outpatient administration for teclistamab SUD (31% vs 18%). During SUD, higher proportions of early initiators than recent initiators had an observed CRS event (41% vs 34% per ICD-10-CM codes and 35% vs 30% per Keating algorithm). Majority of CRS events were grade 1 or 2 in both early and recent initiators (87% and 85%, respectively, per ICD codes). Observed ICANS rates were similar in early and recent initiators (11% vs 10% per ICD codes and 6% vs 5% per symptom codes). Conclusions In this study using nationally representative real-world all-payer claims data of teclistamab-treated patients in the US, early initiators were younger, sicker, and more heavily pretreated (including prior commercial anti-BCMA therapies) as compared to recent initiators. A higher proportion of recent initiators were observed to have received SUD in the outpatient setting. Recent initiators had lower rates of CRS than early initiators. These evolving patient characteristics and outpatient SUD models likely reflect growing familiarity with teclistamab. Real-world outcomes with teclistamab may improve with time as more fit patients receive this therapy. Larger and longer follow-up are needed to further understand changes over time. References 1. Dima D, et al. Transplant Cell Ther. 2024;30(3):308 e1-308 e13. 2. Mohan M, et al. Blood Cancer J. 2024;14(1):35. 3. Banerjee R, et al. Blood. 2023;142(Suppl 1):5087-5087. 4. Keating SJ, et al. Transplant Cell Ther. 2022;28(7):404 e1-404 e6.