Presenting Author: James A. Davis, PharmD, BCOP, Hollings Cancer Center, The Medical University of South Carolina, Charleston, SC
Co-Authors: Katelynn Granger, PharmD, and Kimberly M. Green, DO, Hollings Cancer Center, The Medical University of South Carolina, Charleston, SC; Jordan Snyder, PharmD, BCOP, and Zahra Mahmoudjafari, PharmD, MBA, BCOP, FHOPA, University of Kansas Cancer Center, Westwood, KS; Mikhaila Rice, PharmD, BCOP, Jack Khouri, MD, and Joslyn Rudoni, PharmD, BCOP, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH; Donald C. Moore, PharmD, BCOP, Shebli Atrash, MD, Hailey Hill, PharmD, BCOP, Jessica McElwee, PharmD, BCOP, and Grace Elsey, PharmD, BCOP, Levine Cancer Institute, Charlotte, NC; Christopher Cahoon, PharmD, Kelley Julian, PharmD, BCOP, and Charlotte B. Wagner, PharmD, BCOP, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT; Victoria Nachar, PharmD, BCOP, University of Michigan Rogel Cancer Center, Ann Arbor, MI
BACKGROUND: Teclistamab is a B-cell maturation antigen-directed bispecific antibody approved for use in patients with relapsed/refractory multiple myeloma. In the MajesTEC-1 trial, cytokine release syndrome (CRS) occurred in 72.1% of patients and was primarily managed with tocilizumab.1 Recently, the International Myeloma Working Group released guidelines supporting the use of tocilizumab for low-grade CRS.2
OBJECTIVE: To evaluate the safety and efficacy of CRS management with dexamethasone compared with tocilizumab.
METHODS: In all, 6 US academic medical centers contributed data on 243 patients who started teclistamab as of July 2024. All patients received teclistamab in a step-up dosing manner per the prescribing information. Patients received adverse event management based on institutional protocols. CRS was graded using the American Society for Transplantation and Cellular Therapy criteria.3 Outcomes included incidence and severity of CRS, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS).
RESULTS: Of the 243 patients included, 133 (55%) patients had CRS (41% grade 1; 13% grade 2). Three grade 3+ events resolved with intensive care. At a median follow-up of 8.7 months, the ORR, median PFS, and median OS were 66%, 6, and 14.3 months, respectively. Dexamethasone was used in 23% of patients, tocilizumab in 29%, and dexamethasone and tocilizumab were used in 23% of patients. Of the 30 patients in the dexamethasone and tocilizumab group, 11 received dexamethasone before tocilizumab. Of those 11, 6 received dexamethasone for immune effector cell-associated neurotoxicity syndrome and 2 of the remaining 5 received subsequent tocilizumab due to grade 2 CRS not resolved with dexamethasone.
Of the 31 patients who had CRS in the dexamethasone group, 87% had grade 1 events. Thirteen patients (42%) who received dexamethasone had recurrent CRS after a subsequent teclistamab dose; however, all subsequent events were of the same or lower grade and resolved with a median of 2 (range, 2-5) additional dexamethasone doses.
In the tocilizumab group, 68% and 32% of patients had grade 1 and 2 events, respectively. The majority (92%) of patients received 1 dose of tocilizumab, with 3 patients requiring multiple doses. Six patients (16%) had recurrent CRS after a subsequent dose.
Median duration of CRS was 1 day for both groups, and step-up doses were delayed a median of 1 day in approximately a quarter of patients in both groups (P=.78). ORR, PFS, and OS were similar between the groups.
CONCLUSIONS: Although more patients had subsequent CRS with dexamethasone, CRS was low grade and manageable with repeated dexamethasone. While considering advantages over tocilizumab in regard to availability, ease of use, and cost, this study highlights the feasibility of dexamethasone for the management of CRS in patients receiving teclistamab.
- Moreau P, Garfall AL, van de Donk NWCJ, et al. Teclistamab in relapsed or refractory multiple myeloma. N Engl J Med. 2022;387:495-505.
- 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. Erratum in: Lancet Oncol. 2024;25:e284.
- Lee DW, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625-638.