早期粒细胞集落刺激因子给药在预防发热性中性粒细胞减少中的作用及其对复发/难治性 B 细胞淋巴瘤患者抗 CD19 CAR-T 毒性与疗效的影响

Chimeric Antigen Receptor T cells (CAR-T) are an outbreaking treatment option for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are the most common specific toxicities, while severe neutropenia and infections are often observed as well. From March 2020, early G-CSF prophylaxis at day (D) two post-infusion was systematically proposed.

We then compared patients treated before that date who did not receive G-CSF or who received late (after D5) G-CSF as control group. Patients administered with early G-CSF had similar duration of grade 4 neutropenia but significantly decreased incidence of febrile neutropenia (58% versus 81%, p = 0. 018). Similar rate of toxicities was observed, including overall and grade 3-4 CRS (p = 0. 93 and p = 0. 28, respectively), and overall and grade 3-4 ICANS (p = 0. 62 and p = 0. 88, respectively).

We observed no difference in the quality of CAR T-cells expansion (p = 0. 79, %Cmax), nor in response rate (best ORR, 57. 6% vs 61. 8%, p = 0. 93), nor survival even in a group of patients adjusted by a propensity score.

In conclusion, early G-CSF administration was safe and effective in reducing febrile neutropenia without impact on toxicities nor on anti-lymphoma activity of CAR-T.