Aggressive Supportive Care Following Novel Agents May Reduce Infection

Following treatment with linvoseltamab, BCMA bispecific antibodies, or immunotherapies, aggressive supportive care may be imperative to prevent high-grade infection occurrence, according to Surbhi Sidana, MD.

CancerNetwork® spoke with Sidana, associate professor and hematologist of the Department of Medicine, Division of Blood and Marrow Transplantation and Cellular Therapy at Stanford University, about the results from the phase 1/2 LINKER-MM1 trial (NCT03761108) published in the Journal of Clinical Oncology, in which investigators assessed the efficacy and safety of linvoseltamab in patients diagnosed with relapsed/refractory multiple myeloma.1 The interview followed the recent FDA decision to give linvoseltamab a complete response letter for this application due to a third party manufacturing site issue.

Sidana highlighted the need for adequate supportive care following immunotherapy due to treatment-related infection incidence. Additionally, she stressed the importance of supportive care, particularly with intravenous immunoglobulin, in communities lacking clinical trial experience, where grade 3 or higher infections may occur following treatment with B-cell maturation antigen (BCMA) bispecific antibodies. Furthermore, Sidana suggested reducing the dosing frequency of bispecific antibodies to reduce the risk of infections.

Findings from the 1/2 LINKER-MM1 trial found that treatment with once-weekly linvoseltamab at 200 mg achieved an independent review committee-assessed objective response rate (ORR) of 70.9%, with 49.6% and 63.2% of patients achieving either a complete response (CR) or better or a very good partial response (VGPR) or better. The stringent complete response (sCR) rate was 44%. Median time to response for a CR, VGPR, and PR or better was 8.5 months (range, 1.6-14.1), 2.6 months (range, 0.7-15.7), and 1 month (range, 0.5-6.3), respectively.

Grade 1, 2, and 3 cytokine release syndrome (CRS) occurred in 35%, 10%, and 1% of patients who experienced CRS, with no grade 4 or higher cases observed. Median time to initial CRS onset was 11 hours (range, -1.1 to 183.6) with a median resolution time of 15.6 hours (range, 1.0-96.0), primarily occurring during step-up dosing.

Immune effector cell-associated neurotoxicity syndrome (ICANS) was reported in 9 patients (7.7%; grades 1-3, 2.6% each), with these events occurring concurrently with CRS or infusion-related reactions. Furthermore, 74.4% experienced infections (grade 3/4, 35.9%), with frequency and severity increasing over time.

Transcript:

[What] I want to highlight about linvoseltamab and other BCMA bispecific antibodies and immunotherapy in general is the importance of good supportive care. These are very effective agents in terms of efficacy, but the lesson that we learned from the early trials was that infection is a big signal. We have to be very aggressive, especially as these treatments move into the community where they might not have experience with clinical trials. We have to be very aggressive with infection prophylaxis, including using drugs for zoster prophylaxis [and] PJP [pneumocystis jiroveci pneumonia] prophylaxis, because cases of PJP pneumonia were seen. We have to be very aggressive with intravenous immunoglobulin, which is very effective in preventing grade 3 or higher infections in patients treated with BCMA bispecific antibodies. [We] have to be careful.

Also, in the real world, a lot of us are reducing the frequency of these agents. In the teclistamab (Tecvayli) trials (NCT04557098), it was shown that, as you reduce the frequency the risk of infection does go down over time. [These are] very practical aspects that I want to highlight, with not just linvoseltamab, but all BCMA bispecific antibodies.

Reference

Bumma N, Richter J, Jagannath S, et al. Linvoseltamab for treatment of relapsed/refractory multiple myeloma. J Clin Oncol. Published June 16, 2024. doi:10.1200/JCO.24.01008