Linvoseltamab with Carfilzomib/Bortezomib Shows Promise in Early Treatment of Relapsed/Refractory Multiple Myeloma

Regeneron Pharmaceuticals, Inc., a notable biotechnology firm, has revealed promising initial findings from the Phase 1b LINKER-MM2 trial, focusing on linvoseltamab paired with two distinct proteasome inhibitors (PIs), carfilzomib and bortezomib, for treating relapsed/refractory multiple myeloma (MM). This study targeted patients who had not experienced success with previous therapies, specifically those who had undergone two or more lines of treatment and were either resistant to both immunomodulatory drugs (IMiD) and PIs or had been exposed to IMiD, PI, and anti-CD38 monoclonal antibodies. These encouraging results are slated for presentation at the American Society of Clinical Oncology (ASCO) 2025 Annual Meeting.

Salomon Manier, M.D., Ph.D., Professor of Hematology at Lille University Hospital, expressed optimism about the outcomes of linvoseltamab combinations, even in patients previously exposed to the PIs being tested. He anticipates these promising results will continue to develop over time, potentially sustaining the benefits noted in the trial.

The trial's cohort involving carfilzomib demonstrated significant therapeutic responses. All participants had prior experience with PIs, and over half were resistant to at least one. This cohort included individuals with baseline soft tissue plasmacytomas and those aged over 75, marking them as high-risk patients. Among 21 evaluable patients, objective response rates reached 90%, with 76% achieving complete responses. Statistical projections indicated high probabilities of maintaining response and progression-free status at the one-year mark. Further research will compare this treatment combination against conventional therapies in a forthcoming Phase 3 trial.

Regarding safety, common treatment emergent adverse events (TEAEs) included neutropenia, cytokine release syndrome (CRS), diarrhea, and thrombocytopenia. Infections were prevalent, with some severe cases leading to a fatal outcome. Serious adverse events affected a significant portion of participants, and dose-limiting toxicity was observed in certain doses.

The second cohort, involving bortezomib, also showed notable clinical activity with 85% of evaluable patients achieving an objective response, half of whom attained complete remission. The safety profile was similar, with common TEAEs comprising CRS, neutropenia, and thrombocytopenia. Infections affected the majority of patients, with adverse events causing two deaths: one related to treatment-induced pneumonia and another unrelated to the treatment due to COVID-19 complications.

The use of linvoseltamab combined with carfilzomib or bortezomib remains investigational and lacks approval from regulatory authorities. Linvoseltamab, branded as Lynozyfic™ in the European Union, is sanctioned for specific use in adults who have undergone multiple prior therapies without success. Meanwhile, in the United States, the FDA is reviewing linvoseltamab for adults with relapsed/refractory MM, with a decision expected by mid-2025.

Multiple myeloma, the second most prevalent blood cancer, poses significant health challenges, with thousands of new cases diagnosed worldwide annually. The cancer is characterized by malignant plasma cells that impair healthy blood cell production and can cause severe organ damage. Although advancements have been made in treatment, MM remains incurable, necessitating ongoing therapeutic development.

The LINKER-MM2 trial is an open-label study assessing linvoseltamab in combination with various cancer treatments for relapsed/refractory MM. The trial features novel therapeutic combinations alongside standard treatments, focusing on determining dose-limiting toxicities and treatment emergent adverse events as primary endpoints, with secondary endpoints evaluating response rates and progression-free survival.

Regeneron continues to research linvoseltamab through various trials, exploring its potential both as a standalone treatment and in combination with other therapies across different stages of MM. Their expansive clinical development program aims to advance cancer treatment solutions, pushing boundaries with innovative approaches.