Impact of Granulocyte Colony Stimulating Factor Use Following CD-19 Chimeric Antigen Receptor T-Cell Therapy

CD-19 chimeric antigen receptor T-cell therapy (CAR-T) has improved outcomes in relapsed/refractory B-cell malignancies but is associated with cytokine-mediated toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hematologic toxicities, and infection. Neutropenia is common following CAR-T and varies in duration. Granulocyte colony-stimulating factor (G-CSF) is used to support neutropenia following CAR-T. However, its use within 14 d post-CAR-T is debated due to concerns it may contribute to CRS and ICANS. Data on the efficacy and safety of G-CSF after CAR-T remain inconclusive with no consensus on its use. The objective of this study was to evaluate the difference in CRS or ICANS development and neutropenia outcomes in patients who received G-CSF within 14 d post-CAR-T versus beyond 14 d. This was a retrospective study evaluating patients ≥ 18 yr who received commercial anti-CD-19 CAR-T therapy from December 1, 2019, through June 30, 2024, at Vanderbilt University Medical Center (VUMC) or Veterans Affairs Tennessee Valley Healthcare System (TVHS). Patients were divided into an early cohort (first G-CSF ≤ d +14) and a late/no cohort (first G-CSF > d +14 or none). Primary outcomes were the incidence of CRS and ICANS. Secondary outcomes included severity of CRS and ICANS, duration of neutropenia, and incidence of early (30 d) and late (90 d) neutropenia. Outcomes were compared across early and late/no G-CSF groups with logistic regression or a proportional odds model as appropriate, with propensity score adjustment for treatment center differences. One hundred fifty-seven patients were included in the analysis (61% early, 39% late/no G-CSF). Most patients were white (81%), male (74%) and received axicabtagene ciloleucel (69%). The most common indication for CAR-T cell therapy was diffuse large B-cell lymphoma (69%) after a median of 3 (IQR 2 to 4) prior lines of therapy. The primary outcome of CRS occurred in 92.7% of the early G-CSF group versus 75.4% of the late/no G-CSF group, though the odds were not significantly different in the adjusted analysis (OR 1.92, 95% CI 0.54 to 6.84, P = 0.317). ICANS occurred in 58.3% of early group versus 41.0% of late/no group patients and was also not statistically significant (OR 1.76, 95% CI 0.71 to 4.36, P = 0.223). Although not statistically significant, higher-grade CRS was more likely in the early group (OR 1.93, 95% CI 0.81-4.57, P=0.136). Grade 3 or 4 ICANS occurred in 24.0% of early and 29.5% of late/no G-CSF patients, with no significant difference. Duration of neutropenia in the first 30 d and incidence of early and late neutropenia were similar between groups. Using G-CSF within 14 d post-CAR-T does not increase the risk of CRS or ICANS compared to use after 14 d or no use. The study found no significant difference in severity of CRS or ICANS, duration of neutropenia, or incidence of early and late neutropenia. This questions the utility of G-CSF for CAR-T patients, as it was not shown to improve neutropenia outcomes.