FDA Approves Linvoseltamab for Adults with R/R Multiple Myeloma

Linvoseltamab received accelerated FDA approval for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.¹

Results from the pivotal phase 1/2 LINKER-MM1 study serve as the basis for the approval. In the study, linvoseltamab demonstrated an objective response rate (ORR) of 70% and a complete response (CR) rate of 45%, as assessed by an independent review committee.

“Myeloma has become an increasingly complex space, especially in the relapsed setting.  Bispecific antibodies have been approved in one way and utilized in the clinic in a somewhat different way; [they are] given q2 and q4 weeks in non-standard/non-studied ways.  This approval allows for planned q2 and q4 week dosing with preplanned analysis and confirmation of a more optimal strategy.  With monthly dosing built in at week 24, we allow patients to only have to come into the clinic once a month for extremely effective therapy,” Joshua Richter, MD, associate professor of Medicine, Division of Hematology and Medical Oncology, Tisch Cancer Institute, Mount Sinai, told Blood Cancers Today.

Notably, the median time to response was less than a month (0.95 months [range, 0.5-6 months). Responses appeared durable with the median duration of response (DOR) not reached (95% CI, 12 months to not estimable). There was an 89% estimated DOR at 9 months (95% CI, 77 -95 months) and an estimated 12-month DOR rate of 72% (95% CI, 54-84 months).

Safety results showed that 95% of patients in the study experienced treatment-emergent adverse events (TEAEs), of which 66% were grade 3 or higher. The most common any-grade TEAEs included cytokine release syndrome (37%), fatigue (32%), and anemia (28%). Two patients in the study developed grade 3 ICANS.

“The rates of CRS and ICANS are somewhat lower for this asset when compared with others. However, given the recent NCCN inclusion of prophylactic tocilizumab to reduce rates of CRS with bispecifics, we can utilize this approach to even further reduce the incidence of adverse events,” Dr. Richter explained.

Based on the safety findings in LINKER-MM1 being consistent across the dose levels explored in phase 2, the FDA approved the 200 mg dose to be administered weekly until week 14, when patients transition to a bi-weekly treatment. The approval includes a box warning for the potential for common TEAEs and common laboratory abnormalities, including decreased lymphocyte count, decreased neutrophil count, decreased hemoglobin, and decreased white blood cell count, which occur in 30% of patients.

Linvoseltamab joins two other bispecific T-cell-engaging antibodies approved for RRMM. Dr. Richter stated: “Because there are subtle but important differences in the studies, it is difficult to compare one drug to another.  That being said, linvoseltamab seems to have the highest ORR and the lowest CRS rate, making it a phenomenal option. Furthermore, the step-up strategy is different, which will require less hospitalization, which is favorable on all sides.”