Cevostamab Post-CAR T: Management and Feasibility in Outpatient/Community Care

In a presentation of data from the phase 2 Sequential T Cell-Engagement for Myeloma (“STEM”) trial (NCT05801939), Adam Cohen, MD and colleagues reported on the safety and preliminary efficacy of consolidating standard-of-care B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR T) therapy with the bispecific antibody cevostamab in relapsed/refractory multiple myeloma.

Here, among 27 enrolled patients, the most common any-grade treatment-emergent adverse events (AEs) included hematologic AEs such as lymphopenia, neutropenia, thrombocytopenia, anemia, and febrile neutropenia, as well as infections in over half (52%) of patients.¹ Importantly, cytokine release syndrome (CRS) occurred in 15% of patients, and no dose-limiting toxicities or immune effector cell-associated neurotoxicity syndrome (ICANS) events were observed.

In this interview, Cohen, associate professor of Medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania, outlines the specific practical management protocol required with this regimen with respect to the observed toxicity profile and comments on the regimen’s feasibility in the outpatient and community settings.

Given the prolonged B-cell and plasma cell ablation with this treatment which can give rise to hypogammaglobulinemia, intravenous immunoglobulin (IVIG) replacement is necessary. This replacement therapy is crucial not only while the patient is actively receiving cevostamab, but also for several months or potentially up to a year thereafter. In addition to IVIG, patients must receive antiviral and pneumocystis prophylaxis to mitigate the risks of infection.

Managing hematologic toxicities, particularly cytopenias, is another crucial element. While these toxicities typically resolve once treatment is completed, general awareness is necessary while patients are on the regimen.

“If this [regimen is] adopted, [providers] would need to know to hold drug, give granulocute colony-stimulating factor [GCSF] and make sure that those patients are supported as they get through [the regimen],” Cohen explained in the interview.

Despite the need for careful management, Cohen believes the regimen is feasible in the outpatient setting. Although the initial trial design required a 48-hour hospitalization period for the first step-up dose and full dose, subsequent safety data indicate that hospitalization may not be necessary, given that appropriate systems are in place to evaluate patients quickly in the event of AEs. This confidence stems from the low 15% CRS rate observed in the study, with all cases being grades 1 or 2 events.

Cohen also believes the regimen’s feasibility extends to community practices. Because the risk of CRS essentially disappears after the step-up dosing, and many community practices are already familiar with administering bispecific antibodies, the simple 2-hour IV infusion of cevostamab can readily be translated to community settings, particularly once the first cycle is complete.

REFERENCE

1. Cohen A, Susanibar-Adaniya S, Garfall A, et al. Phase 2 study of cevostamab consolidation following BCMA CAR T cell therapy: preliminary safety, efficacy, and correlative data from the “STEM” (Sequential T Cell-Engagement for Myeloma) trial. Blood. 2025;146(Supplement 1):699-699. doi:10.1182/blood-2025-699