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

Eur J Haematol. 2024 Jan;112(1):137-140. doi: 10.1111/ejh.14087. Epub 2023 Aug 21.

Abstract

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.

Keywords: B-lymphoblastic leukemia; CAR-T cells; Philadelphia chromosome; ponatinib.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antigens, CD19
  • Chronic Disease
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunotherapy, Adoptive
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Receptors, Chimeric Antigen*
  • Recurrence
  • T-Lymphocytes

Substances

  • ponatinib
  • Receptors, Chimeric Antigen
  • Antigens, CD19