Cytokine Release Syndrome in Relapsed/Refractory Multiple Myeloma: Teclistamab Study Overview

In the MajesTEC-1 phase 1/2 study, Teclistamab, a bispecific antibody targeting B-cell maturation antigen and CD3, exhibited an overall response rate of 63.0% among 165 patients with relapsed or refractory multiple myeloma who had undergone extensive prior treatment. The study reported that 72.1% of the 165 patients exhibited cytokine release syndrome (CRS), a recognized manifestation of T-cell redirection. The patients were administered teclistamab at a dosage of 1.5 mg/kg subcutaneously on a weekly basis, following two step-up doses of 0.06 and 0.3 mg/kg. Chronic Rhinosinusitis was evaluated based on the grading criteria established by the American Society for Transplantation and Cellular Therapy. The management of CRS was carried out in accordance with the study protocol, which involved the administration of tocilizumab and/or steroids.

The majority of cases of cytokine release syndrome were observed during the step-up dosing regimen of teclistamab and were classified as grade 1 (50.3% of patients) or grade 2 (21.2% of patients). A solitary instance of grade 3 CRS was documented in a patient with concomitant grade 3 pneumonia. All Common Terminology Criteria for Adverse Events (CTCAE) cases related to the Clinical Research Study were resolved without any treatment discontinuation. In total, 33.3% of the patients experienced more than one cytokine release syndrome event. The recurrence of CRS was observed to be lower when tocilizumab was administered during the first CRS event as compared to when it was not administered (20.0% vs. 62.2%, respectively). The baseline characteristics, including tumor burden and cytokine levels, did not significantly correlate with the incidence or severity of cytokine release syndrome. The results of this study provided evidence for the necessity of proactive preparation and timely intervention in cases of cytokine release syndrome among individuals undergoing treatment with T-cell–engaging bispecific antibodies. The administration of tocilizumab as an intervention for cytokine release syndrome has been observed to reduce the probability of patients encountering subsequent CRS episodes while maintaining the efficacy of teclistamab treatment.

Source:https://acsjournals.onlinelibrary.wiley.com/doi/full/10.1002/cncr.34756#cncr34756-tbl-0001

Clinical Trial:https://clinicaltrials.gov/ct2/show/NCT04557098

Thomas G. Martin, Maria Victoria Mateos, Ajay Nooka, Arnob Banerjee, Rachel Kobos, Lixia Pei, Ming Qi, Raluca Verona, Margaret Doyle MSc, Jennifer Smit MBA, Weili Sun, Danielle Trancucci MSc, Clarissa Uhlar, Niels W. C. J. van de Donk, Cesar Rodriguez/ Detailed overview of incidence and management of cytokine release syndrome observed with teclistamab in the MajesTEC-1 study of patients with relapsed/refractory multiple myeloma/Cancer. https://doi.org/10.1002/cncr.34756