Ponatinib/blinatumomab for relapsed Philadelphia chromosome-positive leukemia as a bridge to allogeneic transplantation

Hematology. 2025 Dec;30(1):2539550. doi: 10.1080/16078454.2025.2539550. Epub 2025 Jul 29.

Abstract

We report three cases of ponatinib/blinatumomab (Pona/BLIN) combination therapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HCT) in patients with relapsed/refractory Philadelphia chromosome-positive acute lymphoblastic leukemia (r/r-Ph + ALL) or lymphoid chronic myeloid leukemia blast crisis (CML-BC). Case 1: A 60-year-old man with Ph + ALL achieved molecular complete remission (mCR) with Pona/BLIN after relapse following initial dasatinib-based treatment and subsequently underwent allo-HCT. Case 2: A 39-year-old man with Ph + ALL achieved hematological CR (hCR) with one cycle of inotuzumab ozogamicin and mCR with Pona/BLIN after post-transplant relapse but developed extramedullary relapse with BCR::ABL-negative clone and underwent a second allo-HCT in non-remission. He subsequently developed hematological relapse. Case 3: A 57-year-old woman initially diagnosed with myeloid CML-BC achieved mCR with chemotherapy regimens and dasatinib maintenance but relapsed as lymphoid CML-BC. She achieved hCR with Pona/BLIN and proceeded to allo-HCT. None of the cases developed grade 3 or higher adverse events during treatment. These cases suggest that Pona/BLIN combination therapy is safe and effective as a bridging strategy to allo-HCT, but extramedullary relapse caused by BCR::ABL-negative blasts can occur.

Keywords: Philadelphia chromosome positive acute lymphoblastic leukemia; Ponatinib; allogeneic hematopoietic stem cell transplantation; blinatumomab; chronic myeloid leukemia.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antibodies, Bispecific
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Female
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Imidazoles* / administration & dosage
  • Imidazoles* / therapeutic use
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive* / therapy
  • Male
  • Middle Aged
  • Philadelphia Chromosome*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Pyridazines* / administration & dosage
  • Pyridazines* / therapeutic use
  • Recurrence
  • Transplantation, Homologous

Substances

  • ponatinib
  • Imidazoles
  • Pyridazines
  • blinatumomab
  • Antibodies, Bispecific