Teclistamab in Relapsed and Refractory Multiple Myeloma Patients - Czech Multi-Center Real World Evidence Analysis

Background Teclistamab is a bispecific antibody designed to target multiple myeloma (MM) cells by simultaneously binding to B-cell maturation antigen (BCMA) on MM cells and CD3 on T cells, facilitating a T-cell-mediated anti-tumor immune response. In the MajesTEC-1 clinical trial, teclistamab demonstrated high efficacy in heavily pretreated relapsed and refractory MM (RRMM) patients. As approximately 40% of MM patients are ineligible for clinical trials, the importance of real-world evidence (RWE) data on the efficacy and safety of teclistamab becomes increasingly significant. Aims We conducted a RWE analysis of teclistamab monotherapy in heavily pretreated RRMM patients. Additionally, we evaluated the efficacy of teclistamab in patients with a reduced dosing frequency. Patients and methods A total of 48 RRMM patients were treated with teclistamab between 2023 and 2024 outside clinical trials across all major Czech hematology centers. Teclistamab was administered either on a standard schedule (weekly for at least six months) or a reduced frequency schedule (every other week), based on the physician's decision. The response was evaluated according to the IMWG Response Criteria. Patient data were collected and analyzed from the Czech Registry of Monoclonal Gammopathies (RMG). Results The median age at the first teclistamab administration was 65.5 years (range 46-76). The median number of previous treatment lines was 5 (range 3-13), with 66.7% (32/48) of patients being penta-refractory (refractory to 2 proteasome inhibitors, 2 IMiDs, and an anti-CD38 antibody). The overall response rate (ORR), defined as partial response (PR) or better was 61.7% (27/44 evaluable patients) and the rate of very good partial response (VGPR) or better was 54.5% (24/44). The median follow-up was 4 months (range 1-13). The median progression-free survival (PFS) was 9.4 months (95% CI: 6.4-NA). Median overall survival (OS) was not reached with 58.9% (95% CI: 43.8-79.2) survival after 12 months. In 25.0% (12/48) of patients, teclistamab was administered every other week. The estimated proportion of patients without a PFS event at 6 months of follow-up was comparable regardless of the dosing schedule (weekly: 62.3% (95% CI: 47.4-81.9) vs. non-weekly: 81.5% (95% CI: 61.1-100.0); p=0.226). The OS data, based on the dosing scheme, were immature. Conclusion Our RWE data demonstrate high efficacy of teclistamab monotherapy in heavily pretreated RRMM population, comparable to MajesTEC-1 registration trial results. Preliminary data suggest that non-weekly dosing could be similarly effective compared to the standard protocol.