Impact of Treatment Modality and Route of Administration on Cytokine Release Syndrome in Relapsed or Refractory Multiple Myeloma: A Meta‐Analysis

Abstract

B‐cell maturation antigen (BCMA)‐targeting immunotherapies (e.g., chimeric antigen receptor T cells (CAR‐T) and bispecific antibodies (BsAbs)) have achieved remarkable clinical responses in patients with relapsed and/or refractory multiple myeloma (RRMM). Their use is accompanied by exaggerated immune responses related to T‐cell activation and cytokine elevations leading to cytokine release syndrome (CRS) in some patients, which can be potentially life‐threatening. However, systematic evaluation of the risk of CRS with BCMA‐targeting BsAb and CAR‐T therapies, and comparisons across different routes of BsAb administration (intravenous (i.v.) vs. subcutaneous (s.c.)) have not previously been conducted. This study utilized a meta‐analysis approach to compare the CRS profile in BCMA‐targeting CAR‐T vs. BsAb immunotherapies administered either i.v. or s.c. in patients with RRMM. A total of 36 studies including 1,560 patients with RRMM treated with BCMA‐targeting CAR‐T and BsAb therapies were included in the analysis. The current analysis suggests that compared with BsAbs, CAR‐T therapies were associated with higher CRS incidences (88% vs. 59%), higher rates of grade ≥ 3 CRS (7% vs. 2%), longer CRS duration (5 vs. 2 days), and more prevalent tocilizumab use (44% vs. 25%). The proportion of CRS grade ≥ 3 may also be lower (0% vs. 4%) for BsAb therapies administered via the s.c. (3 studies, n = 311) vs. i.v. (5 studies, n = 338) route. This meta‐analysis suggests that different types of BCMA‐targeting immunotherapies and administration routes could result in a range of CRS incidence and severity that should be considered while evaluating the benefit–risk profiles of these therapies.