Real-World Analysis of Teclistamab in 115 RRMM Patients from Germany

Abstract

Background Bispecific antibodies and CAR-T cells are currently changing the treatment landscape of relapsed and refractory multiple myeloma (RRMM), having shown high response rates and durable remissions of more than a year in clinical trials. However, some discrepancies to these results have been observed lately, with lower median progression free survival (PFS) and overall survival (OS) in the real-world setting for idecabtagene vicleucel (ide-cel), possibly related to strict entry criteria of the study and known general benefits for patients participating in clinical trials regardless of study arm allocation. Whether this also holds true for Teclistamab, a B-cell maturation antigen (BCMA) x CD3 bispecific antibody approved for treatment of RRMM in 2022 in several countries, has yet to be determined. Therefore, we thought to assess Teclistamab efficacy and tolerability in the real-world setting. Methods Data of 115 patients with RRMM treated with Teclistamab at 18 different German centers from July 2022 to July 2023 were retrospectively collected and analyzed. The patients had received at least one full treatment dose of Teclistamab. Responses were evaluated in accordance with the IMWG response criteria; in addition, near complete response was defined as serological complete remission lacking bone marrow assessment, as this was not always part of clinical routine. In non-secretory disease, response evaluation was based on radiological criteria. Kaplan-Meier methods were applied for time-to-event-analyses. For comparison of survival among groups, the log-rank test and Cox regression analysis were used. For comparison of response rates among groups, the Chi square test was applied. Results The included 115 patients (49 female, 66 male with a median age of 66.0 years) had a median history of MM diagnosis of 6.5 years and were heavily pretreated with a median of 6 (range 3-14) prior lines of therapy. The majority of patients had triple-class (91.3%) or even penta-drug (58.3%) refractory disease. 35.6% (41/115) had received BCMA-directed pretreatment, among them 20 with ide-cel, 21 with belantamab mafodotin and single patients with both or a BCMA-directed study medication. Cytogenetic high-risk features defined as del(17p), t(4;14) and/or t(14;16) and extramedullary disease (EMD) were present in 38.0% and 37.2% of patients, respectively. Around one third of patients had high disease burden with bone marrow infiltration ≥60% (37.0%) or ISS 3 (35.2%) in the latest assessment before initiation of Teclistamab. Overall, a substantial proportion of 40.9% of the treated patients would not have met selected inclusion criteria of the MAJESTEC-1 trial like measurable disease, stable hematopoiesis and kidney function. With median times to response and best response of 4.3 weeks and 8.0 weeks, we observed an ORR, defined as partial remission or better, of 56.8%. 20.9% of all patients reached a near complete or complete response. With a median follow-up of 3.9 months, median PFS was 8.7 months. Median duration of response and median OS were not reached. In the group of patients with BCMA-directed pretreatment, the ORR of belantamab-pretreated patients (70%) was comparable to that in anti-BCMA naïve patients (60.0%), whereas ide-cel pretreated patients showed a significantly lower ORR of 27.8%. Interestingly, PFS did not differ significantly between ide-cel pretreated and ide-cel naïve patients. In further subgroup analyses, the presence of EMD and an ISS of 3 were associated with inferior ORR and PFS in univariable and multivariable analysis. Safety was similar to the experience in MAJESTEC-1. 60.0% of patients developed CRS and 6.9% neurotoxicity with grade 3 or 4 events in 1.7% and 0.9% of patients, respectively. Tocilizumab was administered in 25.2% and dexamethasone in 15.7% of patients. Infections occurred in 49.6% of patients, nearly half of them requiring hospitalization. 53.9% experienced grade 3 or 4 cytopenia according to CTCAE during treatment. Conclusions With an ORR of 56.8% in all patients and 60.0% in anti-BCMA naive patients, Teclistamab showed a similar ORR in the real-world setting to that observed in the MAJESTEC-1 trial. PFS was slightly lower, but our patient collective comprised higher proportions of patients with high risk disease, extramedullary disease, high disease burden, hematopoietic or renal impairment.