Abstract Introduction/background: Cytokine release syndrome (CRS) is one of the most common adverse effects of bispecific antibodies (BsAbs) during the step-up dosing (SUD) phase of treatment. The addition of tocilizumab (Toci) at 8 mg/kg to pre-medication regimen (dexamethasone, acetaminophen and diphenhydramine) proved to be an effective mitigation strategy where CRS rates declined significantly from 72-80% to 14-30%. These findings prompted the National Cancer Comprehensive Network (NCCN) to recommend Toci as a pre-medication for CRS prophylaxis in the recent multiple myeloma guidelines. Based on published evidence regarding cytokine storm prevention with 4 mg/kg of Toci among patients with COVID-19 infections, we are reporting our center's experience using low-dose Toci (Toci-lo) for preventing CRS during the BsAbs SUD phase of treatment. Methods: Patients with relapsed/refractory multiple myeloma (RRMM) who were hospitalized for initiating BsAbs and received prophylactic Toci-lo administered prior to the first SUD per institutional guidelines were included (cohort 1). For comparison, a historic cohort of patients that did not receive Toci prophylaxis during the SUD phase was selected (cohort 2) using the institutional plasma cell disorders database after matching for the following: disease characteristics (high risk cytogenetic features, presence of extramedullary disease, elevated LDH), type of BsAbs, prior exposure to T-cell redirection therapies (TCRT) and absolute lymphocyte count. CRS was graded using the American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria. The Fisher's exact/Chi-square test was used to compare CRS rates between the two cohorts. Univariate/multivariate logistic regression analysis was performed to estimate the CRS risk with Toci prophylaxis. All statistical analyses were performed using IBM SPSS statistics (version 26). Results: 64 patients were included in the analysis (33 in cohort 1 and 31 in cohort 2); baseline characteristics were comparable between the two cohorts except for the number of prior lines of therapy (cohort 1: 5, range: 2-11 and cohort 2: 7, range: 3-12; p=0.01); 18% (n=6) and 19% (n=6) were exposed to TCRTs (chimeric antigen receptor- T cells, CAR T-cells: 2, BsAbs: 2 and both: 2) in cohorts 1 and 2, respectively; high risk cytogenetics 17p del, TP53, gain/amp 1q, t(4;14), t(14;16) and t(14;20) were present in 52% (n=17) of the patients in cohort 1 and 29% (n=9) in cohort 2 (p=0.08). Extramedullary disease was found in 36% (n=12) of patients in cohort 1 compared to 23% (n=7) in cohort 2 (p=0.28). Teclistamab was administered to 58% of the patients in both cohorts 1 (n=19) and 2 (n=18). Talquetamab was administered to 32% (n=11) and 29% (n=9) of patients in cohorts 1 and 2, respectively. The remaining patients in both cohorts received elranatamab (cohort 1: 10% and cohort 2: 13%). The CRS rate was significantly lower in cohort 1 (n=7; 21%, 95% CI:10.7-37.8%) compared to cohort 2 (n=17; 55%, 95% CI: 38.0-70.8%; p=0.009). Based on univariate and multivariate analyses (adjusted for prior lines of therapy), prophylactic use of Toci-low was associated with a significant reduction in the incidence of CRS during the SUD phase with an odds ratio of 0.2 (95% CI: 0.06-0.65; p=0.01). All CRS events were treated with Toci 8 mg/kg. Most of the CRS events occurred following SUD1 (57% in cohort 1 and 58% in cohort 2). The rate of grade 2 CRS was 0% in cohort 1 compared to 17% in cohort 2 (n=3; p=0.50). Recurrent CRS events were noted only in a single patient from cohort 1 and 26.0% (n=6) in cohort 2 (p=0.64). The rate of neurotoxicity/immune effector cell-associated neurotoxicity syndrome (ICANS) was 6% in cohort 1 (n=3) and cohort 2 (n=2). One patient in each cohort developed grade 2 neurotoxicity/ICANS which resolved more than 48 hours following management per institutional guidelines. Cost-effectiveness analysis of Toci-lo will be shared at the ASH meeting. Conclusion: Based on our findings, a single prophylactic Toci-lo proved to be an effective approach which can be utilized as an option to reduce CRS incidence during the SUD phase of BsAbs treatment.
Derkach et al. (Mon,) studied this question.