We looked into the prevalence and effects of anti-CD19 chimeric antigen receptor ( CAR ) T-cell-associated Common Terminology Criteria for Adverse Events( CTCAE ) & ge, grade 3 cytopenia. We found 398 adult patients with large B-cell lymphoma who had received CAR-T cells with axicel( 62 %%) or tisacel( 38 %%) prior to August 2021 and had their cytopenia status documented for the first 100 days in the EBMT CDT registry. 22.3 % of patients had received four or more lines of therapy, compared to the average of two or three. 80.4 % of patients had progressive disease, 5.0 % were stable, and 14.6 % had partial or complete remission. 25.9 % of the patients had previously undergone a transplant. Median age was 61.4 years old( min & ndash, max, IQR = 18.7 / 2, 81, 52.9 %, and 69.5 %).
A cumulative incidence of & ge, grade 3 cytopenia was 9.0 % at 30 days( 95 % CI ( 6. 5 to 12.1 ) and 12.1 % at 100 days following CAR T-cell infusion( 9.5 to 15.5 ). The median period of time from CAR-T infusion to the onset of cytopenia was 16.5 days( min & ndash, max, IQR = 1, NDASH, 90, and( 4 nascent, 29.8 ). 15.2 % and 84.8 % of grade 3 and grade 4 CTCAE cytopenia, respectively, were present. There was no resolution in 47.6 % of cases.
Overall survival( OS )( HR 1.13( 95 % CI 0.74 to 1.73 ), p = 0.57 ) was unaffected by severe cytopenia. Patients with severe cytopenia, however, had a higher rate of relapse( HR 1.52( 95 % CI 1.04 to 2.23 ), p = 0.03, and poorer progression-free survival ( PFS ). Relapse incidence and non-relapse mortality at 12 months after receiving a severe cytopenia diagnosis were 53.6 %( 95 % CI( 40.3 to 71.2 ), 20 %( 95.5 % ( CI( 10.4 to 38.2 )), and 6.5 %( 55.2 to 16.2 ) in those patients who experienced severe cell death within the first 100 days( n = 47 ), OS, and PFS, respectively.
Only one year of CAR-T infusion( HR = 0.61, 95 % CI( 0.39 to 0.95 ), p = 0.028 ), and the total number of treatment lines prior to that induction( one or two lines vs. three or more, HR = 0.41 to 0; 83, f = 0.0013 ) had a significant positive association with the incidence of cytopenia, according to multivariate analysis of severe cellular cyphilia risk factors. Other variables, such as prior transplantation, CAR-T disease status at the time, patient age, and patient sex, did not have a significant impact.
Our data shed light on the prevalence and clinical significance of severe cytopenia following CAR T-cell therapy in the real-world setting of Europe.