Safety and Efficacy of Teclistamab in Patients with Relapsed/Refractory Multiple Myeloma: A Real-World Experience from the US Myeloma Innovations Research Collaborative (USMIRC)

Introduction Teclistamab is a BCMA-directed bispecific antibody approved for relapsed-refractory multiple myeloma (RRMM) on the basis of the MajesTEC-1 trial. The goal of our study was to report clinical outcomes with teclistamab in a real-world RRMM population. Methods Five large US academic centers, part of the USMIRC, contributed data to this multicenter retrospective analysis, which included patients who received teclistamab under a commercial FDA label or an expanded access program between 8/1/22 and 8/15/23. For categorical variables logistic regression analysis was applied. The progression free (PFS) and overall survival (OS) were estimated by Kaplan-Meier method and were analyzed using log-rank tests. In the multivariable context, the Cox proportional hazards model was utilized. Results A total of 106 patients were included; 83% of whom would have been considered ineligible for the MajesTec-1 trial; main reasons were: prior BCMA-directed therapy (BDT) (53%), ECOG performance status (PS) ≥2 (33%), any severe baseline cytopenia (31%), and renal insufficiency (13%). The median number of prior lines of therapy (LOT) was 6 (range 4–17). All patients were triple class exposed, 64% were penta-class refractory, and 53% were exposed/refractory to prior BDT. Cytokine release syndrome was observed in 64% of patients and only one event was grade ≥3. Immune effector cell-associated neurotoxicity syndrome was observed in 14% of patients (three events were grade 3-4). Grade 3-4 hematological toxicities included neutropenia (24%), anemia (19%), and thrombocytopenia (18%). One-third (31%) of patients experienced an infection, with nearly half of these infections graded as severe (grade ≥3). A total of 12 (11%) patients discontinued teclistamab permanently due to treatment-related toxicities (8%) or other reasons (3%) (apart from disease progression or death). The overall response rate (ORR) and complete or better response rate were 66% and 29%, respectively. The ORR was 47%, 68% and 53% for patients with extramedullary disease (EMD), prior BCMA-refractory, and penta-refractory disease, respectively. At a median follow-up of 3.8 months, the median PFS was 5.4 months (95% CI, 3.4-not reached), while median OS was not reached. On multivariate analysis, the factors associated with inferior ORR included: ECOG PS ≥2 (p=0.002), known history of prior EMD (p=0.001), and more than 4 prior LOT (p=0.035). Likewise, patients with ECOG PS ≥2, EMD, and age ≤70 years had inferior PFS on multivariable analysis. Conclusion This is the largest real-world experience of the outcomes of teclistamab for RRMM. Overall, teclistamab was well tolerated with no major safety concerns despite worse performance status and worse cytopenias than the MajestTEC-1 trial population. Our study demonstrates reasonable safety and good efficacy of teclistamab in patients with RRMM treated in the real-world setting.