LINKER-MM1 Trial for Relapsed Multiple Myeloma

Studying the optimal dose of Linvoseltamab in myeloma patients

LINKER-MM1 study presented the efficacy and safety of linvoseltamab, a BCMA bi-specific antibody, in patients with relapsed or refractory multiple myeloma. The study evaluated two dosing cohorts of linvoseltamab at 50 milligrams and 200 milligrams. The overall response rate was 50% for the 50 milligram dose and 71% for the 200 milligram dose, including complete response rate or better of 30%. Patients who achieved complete response or stringent complete response also showed a high proportion of minimal residual disease negativity. The responses were durable, with a median time to response of 0.95 months and a six-month probability of maintaining a response of 84% in the 200 milligram cohort. The most common adverse event was cytokine release syndrome (CRS), occurring in 45% of patients in the 200 mg cohort, the majority of which were grade 1 in severity.   When CRS did occur, it typically started and resolved within 24 hours after treatment during the step-up dosing period. Infection rates were similar between the two dose cohorts. These results support the further development of linvoseltamab in multiple myeloma, and a Phase 3 trial (Linker-MM3) will be initiated.

• The Phase 2 parts of the Linker-MM1 study evaluated the efficacy and safety of linvoseltamab in patients with relapsed or refractory multiple myeloma.
• Linvoseltamab is a bispecific antibody that targets BCMA on plasma cells and CD3 on the T-cell receptor.
• The study included two dosing cohorts: 50 milligrams and 200 milligrams of linvoseltamab.
• The overall response rate was 50% for the 50 milligram dose and 71% for the 200 milligram dose.
• Complete responses were achieved in 30% of patients.
• Among patients with complete responses, 54% had minimal residual disease negativity at a sensitivity of 10^-5.
• Responses were durable, with a median time to response of 0.95 months and a six-month probability of maintaining a response of 84% in the 200 milligram cohort.
• The most common adverse event was cytokine release syndrome (CRS), which occurred in 55% of patients in the 50 milligram cohort and 45% in the 200 milligram cohort.
• Infections were similar between the two dose cohorts, with 62% of patients in the 50 milligram cohort and 60% in the 200 milligram cohort experiencing infections.
• The study supports the further development of linvoseltamab in multiple myeloma, and a Phase 3 trial (LINKER-MM3) will be initiated.

Authors:
Hans C. Lee, Naresh Bumma, Joshua Ryan Richter, Madhav V. Dhodapkar, James E. Hoffman, Attaya Suvannasankha, Jeffrey A. Zonder, Mansi R. Shah, Suzanne Lentzsch, Joseph J. Maly, Jing Christine Ye, Ka Lung Wu, Michelle DeVeaux, Dhruti Chokshi, Anita Boyapati, Anasuya Hazra, Karen Rodriguez-Lorenc, Glenn Scott Kroog, Yariv J. Houvras, Sundar Jagannath

Clinical trial information: NCT03761108 (https://clinicaltrials.gov/ct2/show/NCT03761108)