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Effect of Granulocyte Colony-stimulating Factor on Toxicities After CAR T Cell Therapy for Lymphoma and Myeloma

Abstract

Chimeric antigen receptor T cells (CAR T) are groundbreaking therapies but may cause significant toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias. Granulocyte colony-stimulating factor (G-CSF) is often used to mitigate neutropenia after CAR T, but there is no consensus recommended strategy due to hypothesized, but largely unknown risks of exacerbating toxicities. To investigate the impact of G-CSF, we retrospectively analyzed 197 patients treated with anti-CD19 CAR T for lymphoma and 47 patients treated with anti-BCMA CAR T for multiple myeloma. In lymphoma, 140 patients (71%) received prophylactic G-CSF before CAR T (mostly pegylated G-CSF) and were compared with 57 patients (29%) treated with G-CSF after CAR T or not exposed. Prophylactic G-CSF was associated with faster neutrophil recovery (3 vs. 4 days, P < 0.01) but did not reduce recurrent neutropenia later. Prophylactic G-CSF was associated with increased grade ≥2 CRS (HR 2.15, 95% CI 1.11-4.18, P = 0.02), but not ICANS. In multiple myeloma, prophylactic G-CSF was not used; patients were stratified by early G-CSF exposure (≤2 days vs. ≥3 days after CAR T or no exposure), with no significant difference in toxicities. Future trials should clarify the optimal G-CSF strategy to improve outcomes after CAR T.

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References
1.
Gill S, Brudno J . CAR T-Cell Therapy in Hematologic Malignancies: Clinical Role, Toxicity, and Unanswered Questions. Am Soc Clin Oncol Educ Book. 2021; 41:1-20. DOI: 10.1200/EDBK_320085. View

2.
Hill J, Seo S . How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies. Blood. 2020; 136(8):925-935. PMC: 7441168. DOI: 10.1182/blood.2019004000. View

3.
Abid M . Granulocyte Colony-Stimulating Factor Usage in Recipients of Chimeric Antigen Receptor T-Cell Immunotherapy. J Clin Oncol. 2022; 40(13):1508-1509. DOI: 10.1200/JCO.21.02694. View

4.
Hay K, Hanafi L, Li D, Gust J, Liles W, Wurfel M . Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood. 2017; 130(21):2295-2306. PMC: 5701525. DOI: 10.1182/blood-2017-06-793141. View

5.
Lievin R, Di Blasi R, Morin F, Galli E, Allain V, De Jorna R . Effect of early granulocyte-colony-stimulating factor administration in the prevention of febrile neutropenia and impact on toxicity and efficacy of anti-CD19 CAR-T in patients with relapsed/refractory B-cell lymphoma. Bone Marrow Transplant. 2022; 57(3):431-439. PMC: 8907072. DOI: 10.1038/s41409-021-01526-0. View