Italian Observational Study on CAR-T Therapy for Lymphoma

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.

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)

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.

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.

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.

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.

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.

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.

Non-relapse mortality (NRM) after CAR-T cell therapy: time will be measured as the interval between the date of treatment start and the date of non-relapse death, with censoring at the date of the latest follow-up in alive patients without relapse. NRM cumulative incidence curves will be estimated regarding disease recurrence as competing event, and between groups comparisons will be performed using the Gray test.

CRS and ICANS will be measured according to ASCTC. Other toxicities will be measured according to CTCAE.

Bridging therapy will be analysed in terms of safety as per adverse event occurrence (according to CTCAE).

Bridging therapy will be analysed in terms of efficacy in terms of response achievement compared to response assessment prior to bridging therapy.

In case of relapse after CAR-T, data regarding salvage therapy will be collected in terms of reponse (PFS)

In case of relapse after CAR-T, data regarding salvage therapy will be collected in terms of survival (OS).

Time form screening to infusion will be compared between CAR-T products, disease response will be evaluated in terms of CR, PR and SD.

Study popoulation will be analysed in terms of reponse and type CAR-T product.

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.

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

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

Evaluate the persistence of CAR-T after administration

In our study, the PET scans will be collected and anonymized. A central review with analyses of quantitative parameters will be performed. Evaluation of baseline tMTV calculated by MTV4 method which automatically segments area with SUV ≥4.0.

In our study, the PET scans will be collected and anonymized. A central review with analyses of quantitative parameters will be performed. Dmax between baseline and +30 and +90 after CAR-T cells infusion

In our study, the PET scans will be collected and anonymized. A central review with analyses of quantitative parameters will be performed. Dmax bulk is the maximum distance to the bulk and we wil analyse its change between baseline and day +30 and +90.