Dataset Information

Venetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant.

ABSTRACT: The role of allogeneic hematopoietic cell transplant (allo-HCT) as consolidation after initial venetoclax therapy and the efficacy of venetoclax salvage therapy for relapse after allo-HCT in patients with acute myeloid leukemia (AML) are unclear. We conducted a retrospective study of patients with AML or myelodysplastic syndrome (MDS) who received venetoclax either before or after allo-HCT at Memorial Sloan Kettering Cancer Center and Yale University from 11 August 2016 to 16 November 2020. Among 39 heavily pretreated patients who received venetoclax before allo-HCT, median OS from allo-HCT was not reached after a median follow up of 12.5 months resulting in a 12-month OS estimate of 79.0%. In 37 patients who had received venetoclax-based combinations as salvage therapy after allo-HCT, the overall response rate was 32% with a median OS of 4.7 months (12-month OS estimate: 43.4%). Four patients underwent a second allo-HCT following venetoclax-based salvage therapy suggesting it as a potential salvage treatment option.

SUBMITTER: Bewersdorf JP

PROVIDER: S-EPMC9012492 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Venetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant.

Bewersdorf Jan Philipp JP Derkach Andriy A Gowda Lohith L Menghrajani Kamal K DeWolf Susan S Ruiz Josel D JD Ponce Doris M DM Shaffer Brian C BC Tamari Roni R Young James W JW Jakubowski Ann A AA Gyurkocza Boglarka B Chan Alexander A Xiao Wenbin W Glass Jacob J King Amber C AC Cai Sheng F SF Daniyan Anthony A Famulare Christopher C Cuello Bernadette M BM Podoltsev Nikolai A NA Roshal Mikhail M Giralt Sergio S Perales Miguel-Angel MA Seropian Stuart S Cho Christina C Zeidan Amer M AM Prebet Thomas T Stein Eytan M EM Tallman Martin S MS Goldberg Aaron D AD Stahl Maximilian M

Leukemia & lymphoma 20210903 14

The role of allogeneic hematopoietic cell transplant (allo-HCT) as consolidation after initial venetoclax therapy and the efficacy of venetoclax salvage therapy for relapse after allo-HCT in patients with acute myeloid leukemia (AML) are unclear. We conducted a retrospective study of patients with AML or myelodysplastic syndrome (MDS) who received venetoclax either before or after allo-HCT at Memorial Sloan Kettering Cancer Center and Yale University from 11 August 2016 to 16 November 2020. Amon ...[more]

PMID: 34477024

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Project description:BackgroundVenetoclax 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.ObjectiveTo evaluate the safety and efficacy of a MAC regimen containing venetoclax for high-risk AML.Study designFrom 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.ResultsAt 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%).ConclusionOur study shows that the addition of venetoclax to a MAC allo-HSCT was feasible, safe and effective for high-risk AML patients.

Dataset Information

Venetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant.

Publications

Venetoclax-based combinations in AML and high-risk MDS prior to and following allogeneic hematopoietic cell transplant.

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