The impact of granulocyte colony stimulating factor on patients receiving chimeric antigen receptor T ‐cell therapy

The impact of granulocyte colony stimulating factor on patients receiving chimeric antigen receptor T-cell therapyTo the Editor:Infectious complications following immunosuppressive therapy increase morbidity and mortality in patients combatting malignancy. 1 The inverse relationship between circulating leukocyte levels and infection potential places patients with prolonged and profound neutropenia at greatest infection risk. 2 Granulocyte colony stimulating factor (GCSF) after aggressive chemotherapy is a supportive measure recommended to reduce neutropenia intensity and ultimately abrogate infection.Chimeric antigen receptor T-cell (CAR-T) therapy represents a major advancement in the management of refractory or relapsed malignancies.3 Patients receiving CAR-T therapy have multiple factors that impair their immunity and increase infection risk.4 The theoretical potential for GCSF to exacerbate cytokine release syndrome (CRS) prompted guidelines to recommend against administering GCSF within 14 days after CAR-T infusion.5 However, few studies exist that characterize outcomes after CAR-T therapy and the ultimate impact of concurrent GCSF remains unknown.6 Our primary objective was the comparison of neutrophil kinetics between patients who did and did not receive GCSF after axicabtagene ciloleucel.Secondary outcomes included comparing CAR-T therapy-related toxicity characteristics and infection rates.This Mayo Foundation Institutional Review Board approved retrospective analysis evaluated consecutive, adult cancer patients who received commercial axicabtagene ciloleucel between January 2018 and December 2020.Patients actively participating in a CAR-T clinical trial, considered a vulnerable population, or refusing research participation were excluded.All patients provided written informed consent or had consent provided for them by their legal power of attorney prior to data collection.The electronic health record (EHR) data was compiled utilizing a standardized form developed by the investigators.Baseline criteria were established immediately prior to lymphodepleting chemotherapy.Lymphoma diagnosis with subtyping was reported according to World Health Organization classification criteria.7 Relevant laboratory values, medications, and microbiology were abstracted from the time of CAR-T infusion through disease relapse, death, or a maximum of 100 days after infusion.Neutropenia and severe neutropenia were defined as an absolute neutrophil cell (ANC) count below 0.5 Â 10 9 cells/L and 0.1 Â 10 9 cells/L, respectively.1 The ANC recovery occurred when the count exceeded and stayed above 0.5 Â 10 9 cells/L cells for two consecutive days.Also, GCSF was originally prescribed and administered throughout the period of neutropenia until ANC recovery.In April 2019, our institutional cellular therapy practice committee changed from ANC-based GCSF administration, where prescribing occurred at ANC of 0.5 Â 10 9 cells cells/L and GCSF was discontinued after two consecutive days where an ANC measured above 0.5 Â 10 9 cells/L, to an infection-based indication with GCSF prescribing reserved for patients presenting after CAR-T infusion with febrile neutropenia and an increased concern for infection after a thorough evaluation.