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The BCMA-directed bispecific antibody linvoseltamab demonstrated promising results in a phase 2 trial of patients with relapsed/refractory multiple myeloma (RRMM), particularly at the 200-mg dose level. The results of the study were presented at the International Myeloma Society Annual Meeting 2023.
These results were consistent in a subgroup analysis, including among groups that are typically challenging to treat, including older patients, higher stage, and penta-refractory disease.
The phase 2 trial (ClinicalTrials.gov Identifier: NCT03761108) evaluated 2 dose levels: 50 mg or 200 mg given weekly for the first 3 cycles followed every 2 weeks for cycles 4 and 5. In the 50-mg group (n=104), every 2-week dosing was continued from cycle 6 and onward. In the 200-mg group (n=117), patients who achieved at least a very good partial response (VGPR) switched to dosing every 4 weeks from cycle 6 and onward, whereas all other patients continued with every 2-week dosing. Patients in both groups underwent step-up dosing with 24-hour hospitalization with 5 mg on day 1 and 25 mg on day 8.
Patients in the 50 mg cohort with disease progression within 4 to 12 weeks of treatment were allowed to cross-over to 200-mg dosing.
The primary endpoint was objective response rate (ORR) and secondary endpoints included duration of response (DOR), progression-free survival (PFS), minimal residual disease (MRD) status, and overall survival (OS).
At baseline, the median age was 65 in the 50-mg group and 70 in the 200-mg group, with 16.3% and 26.5% of patients, respectively, aged 75 or older. More patients in the 50-mg group were ISS stage III, had a prior autologous transplant, and were triple-, quad-, or penta-refractory. More patients in the 200-mg group had high risk cytogenetics.
ORR was higher in the 200-mg group at 71% compared with 50% in the 50-mg group. In the 200-mg group, the rate of stringent complete response (CR) was 16%, CR was 14%, and VGPR was 29%. In the 50-mg group, the rates were 14% for stringent CR, 7% for CR, and 20% for VGPR.
Of the 8 patients who crossed over from the 50-mg to 200-mg group, 75% achieved a VGPR. With the 200-mg dose, the ORR was 56.3% with EMP, 61.9% with high-risk cytogenetics, 67.7% in patients aged 75 or older, 59.1% in patients with ISS stage III disease, and 60.7% in patients with penta-refractory disease.
The median PFS was not yet reached in the 200-mg group and was 7.9 months in the 50-mg group. The 3- and 6-month PFS was 79.6% and 72.7%, respectively, among patients in the 200-mg group compared with 59.4% and 54.6%, respectively, among patients in the 50-mg group.
In the 200-mg group, the most common grade 3-4 treatment-emergent adverse events (TEAEs) were hematologic, including neutropenia, thrombocytopenia, and lymphopenia. Treatment discontinuation due to TEAEs occurred among 16.2% of patients.
Cytokine release syndrome of any grade occurred among 45.3% of patients, with 1 patient experiencing grade 3-4 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) of any grade developed in 5.9% of patients, with 1.8% of patients experiencing it as grade 3-4. Infections were common, occurring in 59.8% of patients, with 36.8% of cases grade 3 or higher.
“Linvoseltamab 200 mg showed early, deep, and durable responses across subgroups including those difficult to treat,” the authors concluded in their poster. The phase 3 LINKER_MM3 trial with the 200-mg dose level is planned.
Disclosures: One of the study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.
Reference
Richter J, Bumma N, Dhodapkar MV, et al. Evaluation of the efficacy and safety of two different linvoseltamab Phase 2 dose regimens: Results from LINKER-MM1. Presented at IMS 2023. September 27-30, 2023. Abstract P-044.
This article originally appeared on Hematology Advisor
