Italian Observational Study on CAR-T Therapy for Lymphoma

Feasibility of the CAR-T cells treatment in lymphomas in the italian real life practice

Evaluate the feasibility of CAR T-cell treatment in the real-life setting, with particular regard to eligible patients versus those subjected to leukapheresis versus those finally treated. The percentage of patients infused will be estimated as the number of patients infused divided by the total number of those declared eligible; the corresponding exact confidence intervals at 95% will also be estimated.

Efficacy of the CAR-T cells treatment in lymphomas in the italian real life practice

Evaluate the survival outcome of PMBCL, DLBCL, MCL and FL patients treated with CAR T-cells versus those potentially eligible, but excluded from cellular therapy for other causes (either related to the patient or to the manufacturing)

Evaluation of Outcome: Overall Response rate (ORR), according to Lugano criteria.

Overall response rate (ORR): the percentage of responding patients will be estimated as the number of patients with complete response (CR) + partial response (PR) divided by the total number of patients assessable at each specific timepoint (3-6-12-18 months). Patients not assessable for response for any reason will be considered as non-responding in the calculation of the response rate. The exact 95% confidence intervals of the response percentage will also be estimated.

Evaluation of Outcome: Overall survival (OS), according to Lugano criteria.

Overall survival (OS): time will be measured as the interval between the date of CAR-T infusion and the date of death for all causes, with censoring at the date of the latest follow-up in alive patients. OS curves will be estimated with the Kaplan Meier method.

Evaluation of Outcome: Progression free survival (PFS)

Progression-free survival (PFS): time will be measured as the interval between the CAR-T infusion and the date of progression disease (PD), or death, whichever occurs first.

Evaluation of Outcome: duration of response (DoR)

Duration of Response (DoR): for patients who will respond to treatment, the duration of response will be measured as the interval between the response achievement and the date of progression or death, whichever occurs first, with censoring at the date of the latest follow-up in alive patients without progression. DoR curves will be estimated with the Kaplan Meier method.

Characterization of biomarkers of early response (circulating tumor cell free DNA versus PET and CT scans)

To study the circulating cell free DNA modulation during time, besides descriptive statistical analyses, we will use non parametric factorial models for longitudinal data \[Brunner E, Domhof S, Langer F. Nonparametric analysis of longitudinal data in factorial experiments. John Wiley \& Sons 2002, New York\]. Such models were chosen because they allow take into account measurement incompleteness and positive asymmetry of biomarker distribution, and because they are robust to outliers. The models also allow to test the difference in the longitudinal profiles according to specific covariates.

Characterization of toxicity biomarkers

Biomarkers will be analysed in relation to toxicities occurrence on order to identify predictors of toxicity onset and severity

Analysis of the immune reconstitution

Evaluate disease response and immune recovery biomarkers at different time-points up after CAR-T (when clinically indicated or using blood sampling leftover)

Analysis of the CAR-T expression

Evaluate the persistence of CAR-T after administration