Presenting Authors: Victoria Nachar, PharmD, BCOP, University of Michigan, Ann Arbor, MI, and James Davis, PharmD, BCOP, The Medical University of South Carolina, Charleston, SC
BACKGROUND: Cytokine release syndrome (CRS) frequently occurs with BCMA- or GPRC5D-directed bispecific antibodies. Current guidelines (International Myeloma Working Group, mSMART) recommend dexamethasone and/or tocilizumab for low-grade CRS, although the evidence is limited.
OBJECTIVE: To evaluate the safety and efficacy of supportive care alone versus pharmacologic intervention with dexamethasone and/or tocilizumab for CRS management.
METHODS: This retrospective study included 555 patients with relapsed or refractory multiple myeloma from 7 US academic centers that initiated elranatamab, teclistamab, or talquetamab by March 2025. Premedications and step-up dosing (SUD) were per the prescribing information. Adverse event management followed institutional standards. Supportive care included antipyretics, hydration, and/or oxygen. Pharmacologic intervention included tocilizumab (8 mg/kg; maximum, 800 mg) and dexamethasone (4-20 mg per dose). CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per American Society for Transplantation and Cellular Therapy criteria.
RESULTS: Of 555 patients, 36 received elranatamab, 308 teclistamab, and 211 talquetamab. CRS occurred in 55% (grade 1, 38%; grade 2, 15%; grade ≥3, 1.8%), with a median duration of 1 day. The incidence of ICANS was 15%. CRS was managed with supportive care in 87 (28%) patients and with pharmacologic intervention in 219 (72%) patients using dexamethasone (n=68), tocilizumab (n=85), or both (n=66). Supportive care consisted of acetaminophen (90%), hydration (30%), and oxygen (5%). In the pharmacologic intervention group, 71% received acetaminophen (P<.001), 45% hydration (P=.017), and 16% oxygen (P=.017). The median number of dexamethasone doses was 5 (range, 1-34) and of tocilizumab was 1 (range, 1-5). A total of 29 patients received prophylactic tocilizumab; 52% had CRS, mostly grade 1; and 87% were managed with supportive care. ICANS occurred in 45% of patients who received dexamethasone and tocilizumab. The baseline characteristics were similar between the groups. Supportive care patients had more grade 1 CRS (92% vs 61%; P<.001), less grade 2 CRS (8% vs 35%; P<.001), and shorter CRS duration (1.3 days vs 1.8 days; P=.003) than pharmacologic intervention patients. The rates of dose delay (33% vs 36%; P=.304), recurrent CRS (26% vs 32%; P=.306), and hospitalization duration (median, 9 days for both; P=.809) were similar for the supportive care and pharmacologic intervention cohorts. Recurrent CRS in all groups was at the same or lower grade, except for 1 patient who received dexamethasone and tocilizumab and had grade 1 CRS with SUD 1 and grade 2 CRS with SUD 2. The median progression-free survival for both the supportive care and pharmacologic intervention groups was 10 months (P=.83), and the median overall survival was 22.9 months and 17.3 months, respectively (P=.11).
CONCLUSION: Supportive care alone demonstrated similar outcomes to pharmacologic intervention for low-grade CRS, particularly grade 1, which supports its role as a safe, effective initial management strategy that may limit the need for additional intervention.
- Rodriguez-Otero P, Usmani S, Cohen AD, et al. International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma. Lancet Oncol. 2024;25:e205-e216. Errata in: Lancet Oncol. 2024;25:e284; Lancet Oncol. 2025;26:e186.