Aggressive supportive care following treatment with linvoseltamab, BCMA bispecific antibodies, or other immunotherapies is crucial to prevent high-grade infections in patients with relapsed/refractory multiple myeloma. This recommendation comes from insights shared by Surbhi Sidana, MD, following the recent LINKER-MM1 trial results and the FDA's complete response letter for linvoseltamab due to manufacturing issues. The focus is on managing treatment-related infection risks, particularly in settings lacking extensive clinical trial experience.
The LINKER-MM1 Trial and Infection Risks
The phase 1/2 LINKER-MM1 trial (NCT03761108), published in the Journal of Clinical Oncology, assessed the efficacy and safety of linvoseltamab in patients with relapsed/refractory multiple myeloma. The trial revealed an objective response rate (ORR) of 70.9% with once-weekly linvoseltamab at 200 mg. Complete response (CR) or better was achieved in 49.6% of patients, and a very good partial response (VGPR) or better in 63.2%. However, the study also highlighted a significant incidence of infections, with 74.4% of patients experiencing infections (35.9% grade 3/4), increasing in frequency and severity over time.
Importance of Supportive Care
Dr. Sidana emphasized the necessity of aggressive infection prophylaxis, including drugs for zoster and Pneumocystis jirovecii pneumonia (PJP) prophylaxis, as cases of PJP were observed. She also highlighted the effectiveness of intravenous immunoglobulin in preventing grade 3 or higher infections in patients treated with BCMA bispecific antibodies. Cytokine release syndrome (CRS) occurred in some patients (grades 1-3), and immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 7.7% of patients.
Reducing Dosing Frequency
In real-world settings, reducing the frequency of BCMA-targeting agents may also decrease infection risk. Data from teclistamab trials (NCT04557098) suggest that less frequent dosing is associated with a lower risk of infection over time. This practical adjustment can be crucial in managing the balance between efficacy and safety.
Implications for Clinical Practice
The insights from the LINKER-MM1 trial and expert recommendations underscore the importance of comprehensive supportive care strategies when using novel agents like linvoseltamab and other BCMA bispecific antibodies in multiple myeloma treatment. Vigilant infection prophylaxis, intravenous immunoglobulin, and potentially reduced dosing frequencies are key considerations for optimizing patient outcomes and minimizing treatment-related complications.
