Administration of Granulocyte-macrophage colony-stimulating factor enhanced CAR T-cell expansion and cellular immunity recovery without inducing cytokine release syndrome：a retrospective study

Background: Leukopenia and cytokine release syndrome (CRS) are two major toxicities of CAR-T cell therapy. GM-CSF is an ideal candidate treatment for leukopenia except for its potential aggravation of CRS. We hypothesized that the optimal timing of supplemental with GM-CSF in a shortage of host immunity and CAR T-cell was chosen as avoidance of CRS. In the study we evaluated the safety and efficacy of GM-CSF intervention post-CAR T-cell therapy while circulating CAR T-cell declined. Methods Nine patients received GM-CSF therapy who displayed moderate leukopenia with white blood cell counts (WBC) < 3000 cells/mm 3 and absolute neutrophil counts (ANC) < 1500 cells/mm 3 with concomitant declination of circulating CAR T-cell after CAR T-cell therapy. Results The median duration of GM-CSF intervention was 15 days (4–30). CAR T-cell expansion was observed in eight patients (8/9), including cerebrospinal fluid of one patient and peripheral blood (PB) of other seven patients. And the peaks of CAR T-cell levels in cerebrospinal fluid and PB appeared in day 6 and day 7 (2–11) following the initiation of GM-CSF administration. Also, increased white blood cells in PB was observed in all patients. The median onset and duration time of WBC recovery were 9 (1–14) and 17(3–53) days. Moreover, the increment of WBC, neutrophil, lymphocyte and CD3-CD16 + CD56 + natural killer cell in PB was observed. In addition, no CRS or fatal infection occurred during GM-CSF treatment. Conclusion This study provides evidence for the clinical feasibility of combining CAR T-cell therapy with the GM-CSF to treat leukopenia patients with concomitant declination of circulating CAR T-cell.