Venetoclax plus azacitidine and donor lymphocyte infusion in treating acute myeloid leukemia patients who relapse after allogeneic hematopoietic stem cell transplantation

Ann Hematol. 2022 Jan;101(1):119-130. doi: 10.1007/s00277-021-04674-x. Epub 2021 Sep 27.

Abstract

This study aimed to evaluate the efficacy and safety of venetoclax plus azacitidine and donor lymphocyte infusion (DLI) in treating patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Twenty-six AML patients who relapsed after allo-HSCT were enrolled and treated with venetoclax plus azacitidine and DLI. Complete remission with incomplete recovery (CRi), partial remission (PR), and objective remission rate (ORR) were assessed, and then event-free survival (EFS) and overall survival (OS) were evaluated. Besides, adverse events were documented. Additionally, whole exome sequencing was performed in bone marrow samples. The CRi, PR, and ORR rates were 26.9%, 34.6%, and 61.5%, respectively. The median time of EFS and OS was 120 (95% CI: 71-610) days and 284.5 (95% CI: 81-610) days, respectively. The most common adverse events were hematologic system adverse events including agranulocytosis, anemia, and thrombocytopenia, while the adverse events of other systems were relatively less and milder. In addition, no serious adverse events existed. Of note, there were 6 (23.1%) patients who developed GVHD. As for gene mutation, 49 mutated genes were found, which were categorized as first-, second-, and third-class mutations, and then further analysis revealed that the first-class mutations were not correlated with EFS or OS. Additionally, the most frequent mutated genes were FLT3, CEBPA, DNMT3A, KIT, KRAS, and NRAS. Venetoclax plus azacitidine and DLI is efficient and tolerant in treating patients with relapsed AML after allo-HSCT, implying this combined therapy as a potential treatment option in the studied patients.

Keywords: Allo-HSCT; Azacytidine; Donor lymphocyte infusion; Relapsed acute myeloid leukemia; Venetoclax.

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Azacitidine / therapeutic use*
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use*
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Leukemia, Myeloid, Acute / therapy*
  • Lymphocyte Transfusion*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / therapy
  • Sulfonamides / therapeutic use*
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Sulfonamides
  • Azacitidine
  • venetoclax