Exploring steroid prophylaxis to mitigate CRS: Enhancing access to bispecific antibodies in RRMM.

Abstract

e19537 Background: Talquetamab, an FDA-approved bispecific antibody (bsAb) for relapsed/refractory multiple myeloma (RRMM), demonstrates an ORR >70% and a 24-month OS rate of 67%. However, CRS rates exceed 70%, with 29%, 44%, and 33% after step-up doses (SUDs) 1, 2, and 3, respectively. Guidelines recommend inpatient monitoring with 48-hour intervals between SUDs due to high CRS rates. Similarly, high CRS rates and need for close monitoring are observed with FDA-approved bsAbs for melanoma and lung cancer, necessitating generalizable strategies to increase bsAb uptake. Prophylactic tocilizumab (toci) reduces CRS rates, but its cost and availability restrict broad use. BsAbs like epcoritamab use post-SUD steroid prophylaxis to mitigate CRS. This study evaluates the role of prophylactic (CRSppx) steroids—dexamethasone (dex) administered between SUDs—in reducing CRS in patients (pts) receiving talquetamab (Tal). Methods: This single-center retrospective study included RRMM pts who completed SUD and received ≥1 treatment dose of Tal from 8/9/23 to 12/31/24. CRSppxwas defined as the group of pts who received dex between each SUD, in addition to standard pretreatment dex. Results: Of the 26 pts who received Tal, 13 received CRSppx. Median age was 65 in CRSppx vs. 70 in standard of care (SOC). High-risk cytogenetics were present in 54% (CRSppx) vs. 62% (SOC). R-ISS stages I, II, and III were 60%, 40%, and 0% (CRSppx) vs. 22%, 33%, and 44% (SOC). Extramedullary disease was present in 6 CRSppx vs. 3 SOC pts; CNS involvement was present in 2 CRSppx pts. Both groups had 1 pt with plasma cell leukemia. Median prior lines of therapy were 7 (CRSppx) vs. 8 (SOC); 85% were penta-refractory in both groups. Median CRSppx dose of dex was 8 mg (range 4 – 10). Any-grade CRS occurred in 4/13 (31%) CRSppx vs. 10/13 (77%) SOC pts; 96% were grade 1 and managed with dex. One CRSppx pt had grade 2 CRS requiring toci, while 2 SOC pts required toci due to persistent CRS despite dex use. No CRS recurrence was noted in CRSppx pts vs. in one SOC pt. One CRSppx pt had concerns for ICANS, though this was confounded by limited pt literacy. Median LOS was 8 days (CRSppx) vs. 9 days (SOC). Any-grade infections occurred in 1 CRSppx vs. 5 SOC pts. 30d-readmission rate was 2/13 (15%) in CRSppx (1 associated with CRS) vs. 3/13 (23%) in SOC. 11 CRSppx and all SOC pts were evaluable for response. At 5.5 months median follow-up, ORR was 91% (70% VGPR) in CRSppx vs. 70% (78% VGPR) in SOC. Disease progression occurred in 2 CRSppx vs. 7 SOC pts. Conclusions: Prophylactic steroids reduced CRS incidence while maintaining high response rates and low infection and readmission rates. This approach could facilitate safe outpatient bsAb administration, improving accessibility in resource-limited settings. Further research is needed to validate these findings, assess steroid-related side effects, and refine dosing. CRSppx has broad applicability with growing use of bsAbs across various tumor types.