The Real Life Accessibility to CAR T-Cell Therapy: Current Experience in the Only Active Center in Italy

BACKGROUND. Axicabtagene ciloleucel and tisagenlecleucel have been approved by FDA and EMA for the treatment of relapsed/refractory diffuse large B-cell and mediastinal Lymphoma (NHL) patients (pts). Selection of pts who can benefit the most from these novel treatments with a low risk of life-threatening toxicities is currently a matter of discussion and outside clinical trials the selection of pts is up to clinicians of the CAR T-cell team in several countries. However, based on the results and follow up of clinical trials and the US reports about real life treatment with CAR T-cells, it is emerging that an expert clinical assessment and application of some inclusion criteria could optimize the success of therapy and minimize the severity of adverse events.

AIMS.We are conducting a single center prospective observational trial to evaluate the accessibility and feasibility of CAR T-cells treatment among the population of NHL pts potentially eligible to this therapy.

METHODS. Since September 2018 we have prospectively registered all pts referred at our center for CART-cells eligibility evaluation either for the enrollment in clinical trials or in the contest of the expanded access program (EAP) open for enrollment since February 2019 at our Institution. We have recorded clinical data including disease characteristics, comorbidities, history and present disease status at imaging. Patients were evaluated and screened for inclusion/exclusion criteria of the CAR T-cells program available at that moment and planned for treatment.

RESULTS. Fifty-four pts with relapsed or refractory NHL potentially eligible to treatment according to EMA were recorded in 10 months. Median age was 48 yrs (range, 20 - 70). Thirty-nine pts were affected by DLBCL and 15 by PMBCL, all pts were refractory or relapsed to at least two chemotherapy regimens, median number of previous therapy was 3. Overall, among the 54 pts referred to our center only 7 pts (13%) have been enrolled in CAR T-cells programs (4 pts treated, 2 pts are waiting for infusion, one is in screening for a protocol) whereas other 11 (20%) have been considered eligible for CART-cells treatment but are still waiting for availability of treatment-slots.

On the contrary 36 pts were considered not eligible. Seventeen pts (31%) were excluded after the first CAR T cell team visit because of rapidly progressive disease, or ECOG >1 or lymphoma mass larger than 20 cm and 7 pts (13%) were excluded for comorbidities. Nine pts requiring a treatment in a short time period were shifted to other strategies (conventional or experimental) and 3 pts were lost at follow-up.

Overall 18 pts in 10 months (33%) have been considered eligible but only 7 out of 18 have been treated, remaining pts are waiting for the treatment. One third of pts have been excluded and cardiopathy, uncontrolled progressive disease and poor performance status represent the major causes for not being eligible to treatment. More criteria such as high ferritin levels, total tumor volume and active infections will delineate even better the patient population really receiving the infusion.

CONCLUSIONS. Among all pts with relapsed and refractory NHL referred at our Center only 33% presented clinical and disease characteristics suitable for CAR T-cells treatment. Moreover, the majority of eligible pts are at the risk of becoming ineligible because of poor disease control. The time needed to plan the apheresis and the 4-5 weeks period to obtain CAR T-cells is a major obstacle to a larger applicability of this strategy, therefore exclusion of pts with large tumor mass and with rapid progressive disease is indicated. Probably, CAR T-cells treatment needs to be planned earlier in the disease course to optimize the outcome. In Italy the feasibility over the last 10 months of CAR T-cells treatment has been largely unsatisfactory and primarily limited by the lack of commercial products. Our observational study is ongoing.