Addition of venetoclax to myeloablative conditioning regimens for allogeneic hematopoietic stem cell transplantation in high-risk AML

Ann Med. 2023 Dec;55(1):388-400. doi: 10.1080/07853890.2022.2164610.

Abstract

Background: Venetoclax monotherapy is an effective option for patients with acute myeloid leukemia (AML). Venetoclax has also been used in non-myeloablative conditioning allogeneic hematopoietic stem cell transplantation (allo-HSCT) for high-risk AML with a tolerable toxicity profile. However, the efficacy and safety of a venetoclax-containing myeloablative conditioning (MAC) allo-HSCT regimen for high-risk AML have not been evaluated.

Objective: To evaluate the safety and efficacy of a MAC regimen containing venetoclax for high-risk AML.

Study design: From 25 February 2021 to 4 September 2022, a total of 31 patients with high-risk AML who underwent allo-HSCT and a MAC regimen with venetoclax were analyzed.

Results: At the time of transplantation, 21 patients were in first complete remission (CR1), 4 were in a second complete remission (CR2), and 6 in non-remission (NR). Twenty-four patients (77.4%) were minimal residual disease (MRD)-positive before transplant. The FLT3-ITD gene mutation was present in 51.6% of patients. NUP98 rearrangement, MLL rearrangement or MLL-PTD and DEK::CAN fusion genes were found in 5 (16.1%), 7(22.6%) and 2 (6.5%) patients, respectively. Twenty-nine (93.6%) patients underwent haploidentical allo-HSCT. The median follow-up time was 278 days (range: 52-632 days). The 100-day cumulative incidence of grade 3 to 4 acute graft-versus-host disease (aGVHD) was 16.1% (95%CI, 7.2-36.0%). The 180-day cumulative incidence of moderate to severe chronic graft-versus-host disease (cGVHD) was 7.1% (95%CI, 1.9-26.9%). Cumulative incidence of 100-day cytomegalovirus (CMV) viraemia and 100-day Epstein-Barr virus (EBV) viraemia was 61.6% (95%CI, 46.5-81.4%) and 3.2% (95%CI, 0.4-22.2%), respectively. The 600-day overall survival (OS) and leukemia-free survival (LFS) were 80.9% (95%CI, 63.5-93.6%) and 81.3% (95%CI, 64.2-93.7%), respectively. The 600-day relapse incidence (RI) and non-relapse mortality (NRM) was 6.9% (95%CI, 1.8-26.3%) and 11.7% (95%CI, 3.9-35.0%).

Conclusion: Our study shows that the addition of venetoclax to a MAC allo-HSCT was feasible, safe and effective for high-risk AML patients.

Keywords: Acute myeloid leukemia (AML); allogeneic hematopoietic stem cell transplantation (allo-HSCT); myeloablative conditioning (MAC); venetoclax.

MeSH terms

  • Chromosomal Proteins, Non-Histone
  • Cytomegalovirus Infections*
  • Epstein-Barr Virus Infections* / complications
  • Graft vs Host Disease* / epidemiology
  • Graft vs Host Disease* / etiology
  • Graft vs Host Disease* / prevention & control
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Herpesvirus 4, Human
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Leukemia, Myeloid, Acute* / therapy
  • Oncogene Proteins
  • Poly-ADP-Ribose Binding Proteins
  • Retrospective Studies
  • Transplantation Conditioning / adverse effects
  • Transplantation, Homologous / adverse effects
  • Viremia / complications

Substances

  • venetoclax
  • DEK protein, human
  • Poly-ADP-Ribose Binding Proteins
  • Chromosomal Proteins, Non-Histone
  • Oncogene Proteins