Clinical Outcomes in Black Patients with Relapsed/Refractory Multiple Myeloma Following Talquetamab Treatment: Analyses from the Phase 1/2 Monumental-1 Study

Background: Black individuals have a higher incidence of multiple myeloma (MM) and higher mortality due to MM but are underrepresented in MM clinical trials. Talquetamab (tal) is the first GPRC5D×CD3 bispecific antibody approved for the treatment of patients (pts) with relapsed/refractory multiple myeloma (RRMM) based on data from the MonumenTAL-1 study (NCT03399799/NCT04634552), which showed overall response rates (ORRs) of ≥70% at the recommended phase 2 doses. Preliminary analyses suggest that tal may have a differential safety profile in Black pts, with a potentially higher incidence of on-target, off-tumor effects. We characterized the clinical profile of tal in Black pts in MonumenTAL-1 to determine potential impact on management strategies in this population. Methods: Eligible pts were intolerant to or progressed on established therapies (phase 1) or had ≥3 prior lines of therapy, including ≥1 proteasome inhibitor, ≥1 immunomodulatory drug, and ≥1 anti-CD38 antibody (phase 2). Pts received subcutaneous tal 0.4 mg/kg weekly (QW) or 0.8 mg/kg every other week (Q2W) with step-up doses. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome were graded by ASTCT criteria; all other adverse events (AEs) were graded by CTCAE v4.03. Response was assessed per IMWG criteria. Results: As of June 20, 2024, in the QW (n=143) and Q2W (n=154) cohorts, respectively, 8% (n=12) and 11% (n=17) of pts were Black, and 90% (n=128) and 82% (n=126) were White. Baseline characteristics, including age, International Staging System stage, and cytogenetic risk, were generally similar between groups. In the Q2W cohort, a higher proportion of Black vs White pts had extramedullary disease (41.2% vs 25.4%). In the QW and Q2W cohorts, respectively, median follow-up was 34.6 and 28.6 mo, and ORR was 100% (12/12) and 52.9% (9/17) in Black pts and 71.9% (92/128) and 71.4% (90/126) in White pts. The 12-mo duration of response rates were 50.5% and 53.3% in Black pts and 42.9% and 62.9% in White pts. The 12-mo progression-free survival rates were 61.4% and 30.0% in Black pts and 32.7% and 49.9% in White pts. Rates of grade (gr) 3/4 neutropenia were 41.7% and 17.6% in Black pts and 28.9% and 19.8% in White pts. Rates of gr 3/4 thrombocytopenia were 8.3% and 11.8% in Black pts and 21.9% and 19.8% in White pts. Infections occurred in 66.7% and 58.8% (gr 3/4, 16.7% and 23.5%) of Black pts and 60.2% and 72.2% (gr 3/4, 24.2% and 20.6%) of White pts. CRS was common across groups (75.0% and 70.6% in Black pts; 78.9% and 73.0% in White pts). Taste-related AEs/dysgeusia occurred in 83.3% and 94.1% of Black pts and 71.1% and 69.0% of White pts; 1 Black pt and 2 White pts discontinued tal due to dysgeusia. Skin-related AEs occurred in 91.7% and 82.4% of Black pts and 54.7% and 73.8% of White pts, all gr 1/2; 1 Black pt and 2 White pts discontinued tal due to skin toxicity. Duration of skin-related AEs was 50 and 63 days vs 29 and 39 days in Black vs White pts; more Black pts received concomitant medications for skin-related AEs (75.0% and 58.8%) vs White pts (33.6% and 39.7%). Rates of AEs leading to cycle delay or dose modification were 83.3% and 41.2% in Black pts and 69.5% and 59.5% in White pts; AEs of any kind leading to tal discontinuation occurred in 8.3% and 11.8% of Black pts and 5.5% and 10.3% of White pts. There were no tal-related deaths. Race was not identified as a covariate impacting the pharmacokinetics of tal. Conclusions: Although pt numbers were small, the clinical profile of tal was generally consistent between Black and White pts, with the exception of higher rates of dysgeusia and skin toxicities, and higher ORR in the QW vs Q2W cohort, in Black pts. Further study is needed to confirm these findings and better inform clinical management of Black pts treated with tal.