Case Report: CAR‐T cells and subsequent maintenance with ponatinib in an adult Philadelphia acute lymphoblastic leukemia patient with hematological and extramedullary relapse after allogeneic stem cell transplantation

Relapsed or refractory (r/r) Philadelphia chromosome–positive (Ph+) acute lymphoblastic leukemia (ALL) still represent an unmet clinical need despite the new immune therapies available for these patients. We report the case of a Ph + ALL relapsed one year after allogeneic stem cell transplant. After one DLI was started CAR‐T program with brexucabtageneautoleucel, using as bridging treatment ponatinib, vincristine and prednisone. Brexu‐cel infusion was performed in 2023, without CRS or ICANS onset. One month after Brexu‐cel infusion BM aspirate and CT‐PET showed recovery of full donor chimerism, MRD negativity and complete metabolic remission. Subsequently was started maintenance with ponatinib: at last follow‐up, the patient persisted in leukemia‐free status. CAR‐T cells represent the most powerful treatment for r/r Ph + ALL but there is no consensus about the optimal bridging strategy and also regarding the management algorithm during “post CAR‐T phase”. Here, we report the efficacy of ponatinib as a bridge to anti‐CD19 CAR‐T cell therapy and as post CAR‐T maintenance. Our experience suggests that a preserving approach with TKI associated to low‐dose chemotherapy can be the optimal bridging therapy prior to CAR‐T and that an “MRD‐guided” and “TKI‐based” maintenance strategy can represent the best choice for Ph + ALL which satisfactorily responds to CAR‐T.