CD19 CAR-T 细胞治疗后重度血细胞减少：来自 EBMT 移植并发症工作组的回顾性研究

We investigated the incidence and outcome of anti-CD19 chimeric antigen receptor (CAR) T-cells-associated Common Terminology Criteria for Adverse Events (CTCAE) grade 3 cytopenia. In the EBMT CAR-T registry, we identified 398 adult patients with large B-cell lymphoma who had been treated with CAR-T-cells with axicel (62%) or tisacel (38%) before August 2021 and had cytopenia status documented for the first 100 days. Most patients had received two or three previous lines of therapy, however, 22. 3% had received four or more. Disease status was progressive in 80. 4%, stable in 5. 0% and partial/complete remission in 14. 6%.

25. 9% of the patients had received a transplantation before. Median age was 61. 4 years (min-max; IQR=18. 7-81; (52. 9-69. 5)). The cumulative incidence of grade 3 cytopenia was 9. 0% at 30 days (95% CI (6. 5 to 12. 1)) and 12. 1% at 100 days after CAR T-cell infusion (95% CI (9. 1 to 15. 5)).

The median time from CAR-T infusion to cytopenia onset was 16. 5 days (min-max; IQR=1-90; (4-29. 8)). Grade 3 and grade 4 CTCAE cytopenia occurred in 15. 2% and 84. 8%, respectively. In 47. 6% there was no resolution. Severe cytopenia had no significant impact on overall survival (OS) (HR 1. 13 (95% CI 0. 74 to 1. 73), p=0. 57).

However, patients with severe cytopenia had a poorer progression-free survival (PFS) (HR 1. 54 (95% CI 1. 07 to 2. 22), p=0. 02) and a higher relapse incidence (HR 1. 52 (95% CI 1. 04 to 2. 23), p=0. 03). In those patients who developed severe cytopenia during the first 100 days (n=47), OS, PFS, relapse incidence and non-relapse mortality at 12 months after diagnosis of severe cytopenia were 53. 6% (95% CI (40. 3 to 71. 2)), 20% (95% CI (10. 4 to 38. 6)), 73. 5% (95% CI (55. 2 to 85. 2)) and 6. 5% (95% CI (1.

7 to 16. 2)), respectively. In multivariate analysis of severe cytopenia risk factors, only year of CAR-T infusion (HR=0. 61, 95% CI (0. 39 to 0. 95), p=0. 028) and total number of treatment lines before CAR-T infusion (one or two lines vs three or more, HR=0. 41, 95% CI (0. 21 to 0. 83), p=0. 013) had a significant positive association with the incidence of cytopenia. Other factors, such as previous transplantation, disease status at time of CAR-T, patient age and patient sex, had no significant association.

Our data provide insight on frequency and clinical relevance of severe cytopenia after CAR T-cell therapy in the European real-world setting.