Inferior Outcomes of EU Versus US Patients Treated With CD19 CAR-T for Relapsed/Refractory Large B-cell Lymphoma: Association With Differences in Tumor Burden, Systemic Inflammation, Bridging Therapy Utilization, and CAR-T Product Use.

Real-world evidence suggests a trend toward inferior survival of patients receiving CD19 chimeric antigen receptor (CAR) T-cell therapy in Europe (EU) and with tisagenlecleucel. The underlying logistic, patient- and disease-related reasons for these discrepancies remain poorly understood. In this multicenter retrospective observational study, we studied the patient-individual journey from CAR-T indication to infusion, baseline features, and survival outcomes in 374 patients treated with tisagenlecleucel (tisa-cel) or axicabtagene-ciloleucel (axi-cel) in EU and the United States (US). Compared with US patients, EU patients had prolonged indication-to-infusion intervals (66 versus 50 d; P < 0.001) and more commonly received intermediary therapies (holding and/or bridging therapy, 94% in EU versus 74% in US; P < 0.001). Baseline lactate dehydrogenase (LDH) (median 321 versus 271 U/L; P = 0.02) and ferritin levels (675 versus 425 ng/mL; P = 0.004) were significantly elevated in the EU cohort. Overall, we observed inferior survival in EU patients (median progression-free survival [PFS] 3.1 versus 9.2 months in US; P < 0.001) and with tisa-cel (3.2 versus 9.2 months with axi-cel; P < 0.001). On multivariate Lasso modeling, nonresponse to bridging, elevated ferritin, and increased C-reactive protein represented independent risks for treatment failure. Weighing these variables into a patient-individual risk balancer (high risk [HR] balancer), we found higher levels in EU versus US and tisa-cel versus axi-cel cohorts. Notably, superior PFS with axi-cel was exclusively evident in patients at low risk for progression (according to the HR balancer), but not in high-risk patients. These data demonstrate that inferior survival outcomes in EU patients are associated with longer time-to-infusion intervals, higher tumor burden/LDH levels, increased systemic inflammatory markers, and CAR-T product use.

Psychosocial Pre-Transplant Screening With the Transplant Evaluation Rating Scale Contributes to Prediction of Survival After Hematopoietic Stem Cell Transplantation.

There is no standard in hematopoietic stem cell transplantations (HSCT) for pre-transplant screening of psychosocial risk factors, e.g., regarding immunosuppressant non-adherence. The aim of this prospective study is to explore the predictive value of the pretransplant psychosocial screening instrument Transplant Evaluation Rating Scale (TERS) for mortality in a 3-year follow-up. Between 2012 and 2017 61 patients were included and classified as low (TERS = 26.5-29) and increased-risk group (TERS = 29.5-79.5). Both groups were compared regarding mortality until 36 months after transplantation and secondary outcomes [Medication Experience Scale for Immunosuppressants (MESI); incidence/grade of GvHD]. The increased-risk group (n = 28) showed significantly worse cumulative survival in the outpatient setting (from 3 months to 3 years after HSCT) [Log Rank (Mantel Cox) P = 0.029] compared to low-risk group (n = 29) but there was no significant result for the interval immediately after HSCT until 3 years afterwards. Pre-transplant screening with TERS contributes to prediction of survival after HSCT. The reason remains unclear, since TERS did not correlate with GvHD or MESI. The negative result regarding the interval immediately after HSCT until 3 years could be caused by the intensive in-patient setting with mortality which is explained rather by biological reasons than by non-adherence.