Case report: Deep molecular remissions post two separate CD19-targeted chimeric antigen receptor T-cell therapies do not prevent disease from relapsing in Philadelphia chromosome-positive acute lymphoblastic leukemia.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is an aggressive B-cell malignancy. The management of a relapsed Ph+ ALL patient is challenging. Currently, either allogeneic stem cell transplant (allo-SCT) or CD19-targeted chimeric antigen receptor T-cell (CAR T-cell) are usually employed as salvage modalities for a relapsed patient. However, there are few reports concerning cases that had both allo-SCT and multiple CAR T-cell therapies, and the optimal management of such patients is unclear. Here, we report a relapsed Ph+ ALL male who was first salvaged with autologous CAR T-cell therapy, followed by allo-SCT. Unfortunately, he had a second relapse even with complete molecular remission (CMR) response after the first CAR T and allo-SCT. This patient was then successfully salvaged by a second CAR T-cell product that is donor-derived. However, even with a CMR response once again following the second CAR T-cell therapy and prophylactic donor lymphocyte infusion, he experienced a molecular relapse; ponatinib was employed as the subsequent salvage treatment. He achieved a CMR response following ponatinib and was still in remission at the last follow-up. No ABL kinase mutation was detected during the whole course of the disease. This case indicated that a repeated CD19-targeted CAR T-cell treatment is feasible and may be effective in a relapsed Ph+ ALL patient that had previous CAR T-cell and allo-SCT, even though both CAR T-cell have the same construction. However, even with a deep response after each CAR T-cell therapy and allo-SCT, there is still a very small amount of undetectable leukemic cells. The optimal management of Ph+ ALL patients who have a deep response after a second CAR T-cell therapy deserves further exploration.