Hematopoietic stem cell boost for persistent neutropenia after CAR T-cell therapy: a GLA/DRST study

Abstract

Hematotoxicity after chimeric antigen receptor (CAR) T-cell therapy is associated with infection and death but management remains unclear. We report results of 31 patients receiving hematopoietic stem cell boost (HSCB; 30 autologous, 1 allogeneic) for either sustained severe neutropenia of grade 4 (<0.5 × 109/L), sustained moderate neutropenia (≤1.5 × 109/L) and high risk of infection, or neutrophil count ≤2.0 × 109/L and active infection. Median time from CAR T-cell therapy to HSCB was 43 days and median absolute neutrophil count at time of HSCB was 0.2. Median duration of neutropenia before HSCB was 38 days (range, 7-151). Overall neutrophil response rate (recovery or improvement) was observed in 26 patients (84%) within a median of 9 days (95% confidence interval, 7-14). Time to response was significantly associated with the duration of prior neutropenia (P = .007). All nonresponders died within the first year after HSCB. One-year overall survival for all patients was 59% and significantly different for neutropenia (≤38 days; 85%) vs neutropenia >38 days before HSCB (44%; P = .029). In conclusion, early or prophylactic HSCB showed quick response and improved outcomes for sustained moderate to severe neutropenia after CAR-T.

Figure 1.

(A) Cumulative incidence of response (recovery or improvement), overall survival according to response (B), and duration of neutropenia before hematopoietic stem cell boost (C). A response was observed in 26 patients (84%), and the median time to response after the boost was 9 days (95% CI, 7-14) in all patients. All nonresponders died within the first year after HSCB, showing 1-year OS of 0% vs a 1-year OS of 74% (95% CI, 54-94; P < .001) for responders. The 1-year OS for neutropenia ≤38 days was 85% (95% CI, 65-100) vs 44% (95% CI, 27-61; P = .029) for neutropenia >38 days before HSCB.