P-095: Impact of granulocyte colony-stimulating factor exposure on cytokine release syndrome during bispecific antibody initiation in relapsed/refractory multiple myeloma

Introduction: Bispecific antibodies (BsAb) are a novel class of immunotherapy agents used in the treatment of multiple myeloma. They are associated with notable adverse events including cytokine release syndrome (CRS), cytopenias, and infections. While granulocyte colony-stimulating factors (GCSF) can be used to treat neutropenia and reduce infection risk, little is known about their safety during the BsAb initiation period (during step up doses [SUD] and first treatment dose [FTD]), when patients are at highest risk of CRS. The objective of this study was to assess the impact of GCSF exposure on CRS rates during BsAb initiation.

Methods: We included all patients who received at least one SUD of commercial teclistamab, elranatamab, or talquetamab between November 2022 and April 2024 at Memorial Sloan Kettering Cancer Center. Exposure to GCSF was defined as administration of at least one dose of filgrastim from 48 hours before up to 7 days after BsAb SUD or FTD, or one dose of peg-filgrastim between 7 days prior to up to 7 days after BsAb SUD or FTD. Data collection included patient demographics, disease characteristics/history, and CRS rates/grades. Baseline characteristics were compared using Fisher’s exact or Wilcoxon rank sum tests. Association of CRS and GCSF exposure was evaluated with univariate cox proportional hazard model with GCSF as a time-dependent covariate.

Results: A total of 126 patients were included, of which 18 were GCSF-exposed and 108 were non-exposed. Baseline characteristics were comparable except for baseline absolute neutrophil count/ANC (1.3 x 10⁹/L [IQR 1-2] in GCSF-exposed vs 3 [2-4.4] in non-exposed; p< 0.001). Median prior lines of therapy were 7 (5-9) vs 6 (4-8), p=0.3. This included BCMA-directed therapy in 56% vs 47% (p=0.5) and BsAb therapy in 28% vs 11% (p=0.07). Extramedullary disease (EMD) was present in 54% vs 35% (p=0.2).

Four (22%) patients received GCSF prior to first SUD at a median of 23 hours (14-31), 5 (28%) received GCSF in between SUD/FTD, and 9 (50%) received GCSF after FTD at a median of 75 hours (62-132). The median ANC at time of GCSF exposure was 0.5 (0.4-0.7). An increase in ANC after GCSF by at least 50% was observed in 11 (61%) patients. CRS occurred in 4 (22%) patients after GCSF exposure vs in 53 (49%) of non-exposed patients. There was a trend towards increased CRS after GCSF exposure, although not significant potentially due a limited number of patients in the GCSF-exposed cohort (HR 2.6, 95% CI 0.9-7.1, p=0.07). Grade 2 CRS occurred in 2 (50%) GCSF-exposed patients. No CRS occurred in patients exposed to GCSF after FTD.

Conclusions: Exposure to GCSF during BsAb initiation was not significantly associated with increased risk of CRS. These results suggest that there are no major safety concerns with GCSF administration for neutropenia during BsAb initiation, although larger cohorts are needed to confirm these findings.