Work

P962: Commercial Teclistamab in Anti-bcma Therapy Exposed Relapsed Refractory Multiple Myeloma Patients: the Mskcc Experience.

Year: 2023

Type: article

Abstract: Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Teclistamab (Tec) is the first CD3 x BCMA bispecific antibody receiving accelerated FDA approval for treatment of relapsed or refractory multiple myeloma (RRMM) in patients who have received ≥4 prior lines of therapy, including a PI, IMiD and an anti-CD38 monoclonal antibody. The approval was based on the results of the MajesTec-1 study (Usmani S et al Lancet 2021, Moreau P et al NEJM 2022), demonstrating a 63% overall response rate in a heavily pretreated RRMM population. Patients with prior exposure to anti-BCMA therapies, such as BCMA targeted ADCs, CAR T-cell products and bispecific antibodies were excluded from this study. Aims: Herein, we present our institutional experience with commercial Tec for RRMM including patients with prior BCMA and GPRC5D directed therapies. Methods: We have performed an IRB-approved, retrospective analysis of clinical outcomes of all patients who have received commercial Tec at MSKCC since its approval on 10/26/2022 using the PCD research database. Descriptive analyses were performed for baseline characteristics. The IMWG criteria (Kumar S et al, Lancet Oncol 2016) were used to assess response and define refractoriness to prior therapies. Immune phenotyping of pre-treatment PBMCs was assessed via high-dimensional flow cytometry using lineage, exhaustion, and activation markers. Serum soluble BCMA levels were assessed using an immunoassay. Results: As of 2/27/2023, 26 patients have received commercial Tec and 18 are response evaluable with ≥1 month of clinical follow-up. Median age was 65 (51-80), prior lines of therapy was 8.5 (4-13), time from diagnosis was 7 years (1.5-16), 44% had high-risk cytogenetics, and 33% had EMD. All patients were triple class refractory and 83% were penta-drug refractory. Twelve had prior anti-BCMA therapy (8 Belamaf, 8 BCMA CART, 1 BCMA bispecifisc, 5 with ≥2 anti-BCMA therapies). Among patients with prior exposure to anti-BCMA therapies, median time from last anti-BCMA therapy was 7.2 months. With a median follow-up time of 2.1 months, the median time to best response was 26 days. Overall response rate was 67% (12/18 pts) in all patients and 55% (6/11 pts) in the prior anti-BCMA therapy group. Pts with ≥2 anti-BCMA therapies had a 40% (2/5) response rate to Tec. Clinical benefit rate (CBR) in all patients was 72% (13/18). Cytokine release syndrome was observed in 8/18 patients (44%) during step-up dosing (5/8 with grade 1 and 3/8 with grade 2 CRS) and CBR was 100% in patients with CRS (88% ORR). Additional notable toxicities include 2 patients with grade 2 neurotoxicity that improved with therapy discontinuation. Summary/Conclusion: To our knowledge, this is the first report of commercial Tec in RRMM. Tec remains effective in relapsed or refractory multiple myeloma despite prior exposure to anti-BCMA therapies, though exposure to multiple prior anti-BCMA therapies may be predictive of diminished efficacy. Clinical data on additional patients will be presented at the meeting. Ongoing translational investigations on soluble BCMA levels and patient-specific immune phenotype will also be presented at the meeting. Keywords: Bispecific, Multiple myeloma, relapsed/refractory

Source: HemaSphere

DOI: 10.1097/01.hs9.0000970752.81198.bb