Evaluating the efficacy of commercial teclistamab in relapsed refractory multiple myeloma patients with prior exposure to anti-BCMA therapies.
Authors: Firestone Ross , Shekarkhand Tala , Patel Dhwani , Tan Carlyn Rose Co , Hultcrantz Malin , Lesokhin Alexander M. , Mailankody Sham , Hassoun Hani , Shah Urvi A , Korde Neha , Maclachlan Kylee , Landau Heather Jolie , Scordo Michael , Chung David J. , Shah Gunjan L. , Lahoud Oscar Boutros , Giralt Sergio , Usmani Saad Zafar 
Published: June 2023

8049 Background: Teclistamab (Tec) is the first CD3 x BCMA bispecific antibody (BsAb) 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 BsAbs were excluded from this study. 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 prior therapy refractoriness. Immune profile 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 2/4/2023, 24 patients have received commercial Tec and 15 are response evaluable with ≥1 month of clinical follow-up. Median age was 66 (51-80), prior lines of therapy was 7 (4-13), time from diagnosis was 7 years (1.5-16), 53% had high-risk cytogenetics, and 40% had EMD. All patients were triple class refractory and 80% were penta-drug refractory. Ten had prior anti-BCMA therapy (7 Belamaf, 8 BCMA CART, 1 BCMA BsAb, 5 with ≥2 anti-BCMA therapies). With a median follow-up time of 1.3 months, the median time to response was 16 days. ORR was 60% (9/15) in all patients and 50% (5/10) 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 73% (11/15). None of the responders have progressed at this short follow-up time. Cytokine release syndrome was observed in 7/15 patients (41%) during step-up dosing (5/7 with g1 and 2/7 with g2 CRS) and CBR was 100% in patients with CRS (71% ORR). Other notable toxicities include 2 patients with grade 2 neurotoxicity that improved with therapy discontinuation. Conclusions: To our knowledge, this is the first report of commercial Tec in RRMM. Tec remains effective in RRMM 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.