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.

Keywords:

• Acute myeloid leukemia
• AML
• MDS
• venetoclax
• transplant

Disclosure statement

D.M.P. received research funding from Takeda and served on the advisory board/board of directors for Kadmon, Generon, and Ceramedix. B.C.S. received research funding from Amgen, Janssen, Celgene, Quintiles, Pfizer, CSL Behring, Sanofi, Adienne, Kite, Jazz, and Actinuum. J.W.Y. owns common stock in Amgen, Merck, and Pfizer. B.G. received research funding from Actinium. W.X. received research funding from Stemline Therapeutics. J.G. served as a consultant for the Gerson Lehman Group. A.C.K. served on the Scientific Advisory board for Astellas and consultant for Abbvie. A.D. is a co-inventor of intellectual property related to CD371 CAR T-cell technology and field of use specific for allogeneic cell therapies, licensed by MSK to Caribou Biosciences. Caribou is a private biotechnology company that develops CRISPR technologies and allogenic cell therapies for oncology. S.G. received research funding from Amgen, Actinuum, Celgene, Jansen, Quintiles, Pfizer, CSL Behring, Sanofi, Adienne, Kite, JAZZ, Johnson&Johnson. S.G. served on the advisory committees or Board of Director’s of Amgen, Actinuum, Johnson& Johnson, Jensen, Jazz Pharmaceuticals, Takeda, Novartis, KITE, Spectrum Pharma, BMS, Sanofi, Pfizer, GSK. M.A.P received honoraria from Abbvie, Bellicum, Celgene, BMS, Incyte, KITE, Merck, Nektar Therapeutics, Novartis, Takeda, Omeros. M.A.P. served on the advisory committees or Board of Director’s of Abbvie, Bellicum, BMS, Incyte, Takeda, Novartis, KITE, Merck, Nektar Pharmaceuticals, Servier, NexImmune, Medigene, Omeros, MolMed. M.A.P. received research funding from Amgen, Janssen, Celgene, Quintiles, Pfizer, CSL Behring, Sanofi, Adienne, Kite, Jazz, Actinuum, Incyte, KITE, Miltenyi Biotec. N.A.P. received research funding (all to the institution) from Boehringer Ingelheim, Astellas Pharma, Daiichi Sankyo, Sunesis Pharmaceuticals, Jazz Pharmaceuticals, Pfizer, Astex Pharmaceuticals, CTI biopharma, Celgene, Genentech, AI Therapeutics, Samus Therapeutics, Arog Pharmaceuticals, Kartos Therapeutics. N.A.P. had a consultancy with and received honoraria from Pfizer, Agios Pharmaceuticals, Blueprint Medicines, Incyte, Novartis, Celgene, Bristol-Myers Squib, CTI BioPharma, PharmaEssentia. A.M.Z. received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene/Cardiff oncology, Incyte, Takeda, Novartis, Amgen, Aprea, and ADC Therapeutics. A.M.Z participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Taiho, Seattle Genetics, BeyondSpring, Trovagene/Cardiff Oncology, Takeda, Ionis, Amgen, Janssen, Epizyme, Syndax, Gilead, Kura, Aprea, Janssen, Lox Oncology, Genentech, and Tyme. A.M.Z served on clinical trial committees for Novartis, Abbvie, Geron, Gilead, Kura, Lox Oncology, and Celgene/BMS. A.M.Z received travel support for meetings from Pfizer, Novartis, and Cardiff Oncology. T.P. reports research support from JAZZ, Agios, BMS, and consulting for Genentech, Tetraphase. E.M.S. received research funding from Bayer; was a consultant for Amgen, AbbVie, Seattle Genetics, and Biotheryx; served as a consultant and received research funding from Syndax; was a member of the Board of Directors or advisory committee for PTC Therapeutics and Syros; served as a consultant and was member of the Board of Directors or advisory committee for Astellas Pharmaceutical, Agios Pharmaceuticals, and Genentech; served as a consultant, received research funding, and was a member of the Board of Directors or advisory committee for Daiichi-Sankyo, Celgene Pharmaceuticals, and Novartis; and is a current equity holder in privately held Auron Therapeutics. S.F.C. has consulted for and holds equity interest in Imago Biosciences. M.S.T. received research funding from AbbVie, Cellerant, Orsenix, ADC Therapeutics, Glycomimetics, Rafael, and Amgen; was a member of the Board of Directors or advisory committee for Bioline rx, Daiichi-Sankyo, KAHR, Rigel, Delta Fly Pharma, Oncolyze, Jazz Pharma, Roche, and Novartis; received research funding from and was a member of the Board of Directors or advisory committee for BioSight; has served on advisory boards for Innate Pharmaceuticals, Kura Oncology, and Syros Pharmaceuticals; and has a patent and received royalties from UpToDate. A.D.G. received research funding from Celularity, ADC Therapeutics, Aprea, AROG, Pfizer, and Prelude; received research funding from and served as a consultant for Aptose and Daiichi Sankyo; served as a consultant and member of the Board of Directors or advisory committee for Astellas, Celgene, and Genentech; received research funding from, served as a consultant for, and was a member of the Board of Directors or advisory committee for AbbVie; and received honoraria from Dava Oncology. None of these relationships were related to the development of this manuscript.

The remaining authors declare no competing financial interests.

Additional information

Funding

Amer Zeidan is a Leukemia and Lymphoma Society Scholar in Clinical Research and was also supported by an NCI's Cancer Clinical Investigator Team Leadership Award (CCITLA). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. S. D. W. and M. S. received funding from the MSKCC Clinical Scholars T32 Program under award number [2T32 CA009512-31]. This work was funded by a Conquer Cancer Young Investigator Award [award number GC241610]. Any opinions, findings, and conclusions expressed in this material are those of the author(s) and do not necessarily reflect those of the American Society of Clinical Oncology^® or Conquer Cancer^®. Research reported in this publication was supported by the NCI of the National Institutes of Health under Award Number [P30 CA016359] and Cancer Center Support Grant/Core Grant to Memorial Sloan Kettering Cancer Center [P30 CA008748] The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. A.D.G. received funding from an American Society of Hematology (ASH) Fellow Scholar Award in Clinical Research.