Associate Professor of Medicine Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA New York, New York, United States
Introduction: Linvoseltamab is a BCMA×CD3 bispecific antibody (Ab) that has shown promising efficacy and generally manageable safety in patients (pts) with relapsed/refractory multiple myeloma (MM) (Lee et al. ASCO 2023). To optimize dose selection, two Ph 2 dose cohorts (50 and 200 mg) were studied in LINKER-MM1 (NCT03761108). Here, we report a detailed comparison of results from these two cohorts.
Methods: LINKER-MM1 enrolled adults with MM who progressed on/after ≥3 lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 Ab; the Ph 2 portion also included pts who were ≥triple class (PI/IMiD/anti-CD38 Ab) refractory. A protocol amendment permitted pts who progressed during 4–12 wks on 50 mg to escalate to 200 mg. Primary endpoint was objective response rate (ORR).
Results: This analysis assessed efficacy and safety in 221 pts (200 mg [n=117] vs 50 mg [n=104]; data cut-off, Feb 28, 2023): aged ≥75 yrs, 26% (200 mg) vs 16% (50 mg); non-White race, both 29%; high-risk cytogenetics, 36% vs 24%; extramedullary plasmacytomas, both 14%; bone marrow plasma cells ≥50%, 22% vs 35%; median soluble BCMA, both 377 ng/mL. The majority of pts (74% [200 mg] vs 88% [50 mg]) were ≥triple class refractory. Median duration of follow-up was 5.6 mo (200 mg) and 7.7 mo (50 mg).
ORR was greater at 200 mg (71%) than 50 mg (50%). Higher ORRs were also seen with 200 vs 50 mg across prespecified subgroups, including by age (18–65 yrs, ORR: 66% vs 42%; ≥65–75 yrs, 79% vs 56%; ≥75 yrs, 68% vs 59%), race (White, 73% vs 45%; non-White, 65% vs 64%), disease stage (ISS stage I, 73% vs 53%; stage II, 73% vs 63%; stage III, 59% vs 25%), functional status (ECOG PS 0, 67% vs 51%; PS 1, 73% vs 50%), serum M protein ( < 1.06 g/dL, 84% vs 58%; ≥1.06 g/dL, 57% vs 47%), involved free light chain ( < 536 mg/L, 83% vs 55%; ≥536 mg/L, 54% vs 45%), and refractory (refr) status (triple-refr, 68% vs 50%; quad-refr, 77% vs 52%; penta-refr, 61% vs 48%). Median PFS was 7.9 mo at 50 mg and not reached at 200 mg. Dose was escalated from 50 to 200 mg in 8 pts; 75% achieved a VGPR.
Treatment-emergent AEs (TEAEs) occurred in all pts (Grade [Gr] ≥3: 79%) at 200 mg and 98% (Gr ≥3: 79%) at 50 mg. Overall, the TEAE profile was similar in both cohorts. The most common TEAE for both doses was cytokine release syndrome (200 mg: 45% [Gr 3: 1%] vs 50 mg: 55% [Gr 3: 2%]); other common TEAEs (>30%) were cough (33% vs 32%), neutropenia (32% vs 28%), fatigue (32% vs 29%), diarrhea (32% vs 28%), anemia (27% vs 40%), and arthralgia (26% vs 31%). There were more opportunistic infections at 200 mg (8% vs 2%).
Conclusions: Linvoseltamab 200 mg showed higher efficacy than 50 mg. Notably, high ORRs with 200 mg were seen across subgroups, even in high-risk and high tumor burden subgroups. Supporting the higher dose, some pts who progressed on 50 mg responded after dose escalating to 200 mg. With a similar safety profile across both doses, these data indicate 200 mg as the recommended dose for future studies.
