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. 2025 Mar 31;15(1):50.
doi: 10.1038/s41408-025-01245-5.

Oral decitabine cedazuridine with and without venetoclax in higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia: a propensity score-matched study

Alex Bataller  1 , Koji Sasaki  2 , Samuel Urrutia  3 , Guillermo Montalban-Bravo  2 , Alexandre Bazinet  2 , Kelly Chien  2 , Danielle Hammond  2 , Ian M Bouligny  2 , Mahesh Swaminathan  2 , Ghayas Issa  2 , Nicholas Short  2 , Naval Daver  2 , Courtney D DiNardo  2 , Tapan Kadia  2 , Elias Jabbour  2 , Farhad Ravandi  2 , Gail J Roboz  4 , Michael Savona  5 , Elizabeth A Griffiths  6 , James McCloskey  7 , Olatoyosi Odenike  8 , Aram Oganesian  9 , Harold N Keer  9 , Mohammad Azab  9 , Hagop Kantarjian  2 , Guillermo Garcia-Manero  2
Affiliations

Oral decitabine cedazuridine with and without venetoclax in higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia: a propensity score-matched study

Alex Bataller et al. Blood Cancer J. .

Abstract

Hypomethylating agents (HMA) are indicated in the treatment of higher-risk myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML). The combination of hypomethylating agents with venetoclax (Ven) has demonstrated promising results in these diseases, although randomized clinical trials are needed for validation. In this retrospective study, we compared two matched cohorts of patients with MDS or CMML: one receiving oral decitabine-cedazuridine (DEC-C, n = 73) and one receiving DEC-C and Ven (DEC-C-Ven, n = 51), in three contemporary clinical trials. The aim is to determine the impact of the addition of Ven to HMA in MDS and CMML. Individuals were matched using a propensity score approach that was based on the IPSS-M score and age. All patients had excess blasts; 84% were diagnosed with MDS and 16% with CMML. Most patients had high- or very high-risk disease, according to the revised IPSS-R. The overall response rate was superior in the DEC-C-Ven cohort (90% vs 64%, P = 0.002). The median times to best response were 1.1 and 2.7 months for the DEC-C-Ven and DEC-C cohorts, respectively (P < 0.001). More patients underwent hematopoietic stem cell transplantation in the DEC-C-Ven cohort (47%) than in the DEC-C cohort (16%, P < 0.001). The 4- and 8-week mortality did not significantly differ between the DEC-C and DEC-C-Ven cohorts. Patients in the DEC-C-Ven cohort had a more profound neutropenia at days 15 and 21 of the first cycle. The median overall survival was 24 and 19 months for the DEC-C-Ven and DEC-C cohorts, respectively (P = 0.89), and the median event-free survival durations were 18 and 10 months (P = 0.026). In conclusion, the addition of Ven resulted in improved response rates and outcomes in specific subgroups; prospective clinical trials are needed to confirm these findings.

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Conflict of interest statement

Competing interests: KS reports fees for professional activities from Amgen, Chugai Pharmaceutical, Daiichi Sankyo Company, Novartis, Otsuka Pharmaceutical Co., Ltd, and Pfizer. Kelly Chien declares honoraria from Otsuka Pharma, and consultancy fee from Pfizer Japan. GCI reports consulting or advisory role for Novartis, Kura Oncology, Syndax, NuProbe, AbbVie, and Sanofi, and research funding from Novartis, Syndax, Kura Oncology, Merck, Cullinan Oncology, Astex Pharmaceuticals and NuProbe. NJS has been a consultant for Takeda Oncology, AstraZeneca, Amgen, Novartis, and Pfizer and received research funding from Takeda Oncology, Astellas, and Stemline Therapeutics as well as honoraria from Amgen. CDDi has been a board of directors or advisory committee member for Genmab, GSK, Kura Oncology, and Notable Labs; has received honoraria from Kura, Astellas Pharma, Bluebird Bio, Bristol-Myers Squibb, Foghorn Therapeutics, Immune-Onc Therapeutics, Novartis, Takeda Oncology, Gilead Sciences, and Jazz Pharmaceuticals; is a current holder of stock options for Notable Labs; has been a consultant for AbbVie and Servier; and has received research funding from Servier, Bristol-Myers Squibb, Foghorn, Immune-Onc Therapeutics, Loxo Oncology, Astex Pharmaceuticals, Cleave, and Forma. TMK has been a consultant for AbbVie, Agios, BMS, Genentech, Jazz Pharmaceuticals, Novartis, Servier, and PinotBio; has received research funding from AbbVie, BMS, Genentech, Jazz Pharmaceuticals, Pfizer, Cellenkos, Ascentage Pharma, GenFleet Therapeutics, Astellas Pharma, AstraZeneca, Amgen, Cyclacel Pharmaceuticals, Delta-Fly Pharma, Iterion Therapeutics, GlycoMimetics, and Regeneron Pharmaceuticals; and has received honoraria from Astex Pharmaceuticals. EJ has been a consultant for AbbVie, Adaptive Biotechnologies, Amgen, Bristol-Myers Squibb, Novartis, Pfizer Canada Inc., and Takeda Oncology. FR has received research funding from Amgen, Astex Pharmaceuticals/Taiho Oncology, BMS/Celgene, Syos, AbbVie, Prelude, Xencor, Astellas Pharma, and Biomea Fusion as well as honoraria from Amgen, BMS/Celgene, Syos, AbbVie, and Astellas Pharma; has been a board of directors or advisory committee member for Astex Pharmaceuticals/Taiho Oncology; and has been a consultant for BMS/Celgene, Syos, Novartis, AbbVie, AstraZeneca, and Astellas Pharma. GJR is a consultant for Agios, Amgen, Amphivena, Astex, Celator, Celgene, Clovis Oncology, CTI BioPharma, Genoptix, Immune Pharmaceuticals, Janssen Pharmaceuticals, Juno, MedImmune, MEI Pharma, Onconova, Pfizer, Roche, and Sunesis; receives research funding from AbbVie, BMS, Teva, and Karyopharm; is an advisory board member or consultant for Novartis, AbbVie, BeiGene, BerGenBio, Arcellx, Jazz Pharmaceuticals, Syros, BMS, Genentech, ImmunoGen, AstraZeneca, Kura, Ryvu, Magenta, and Qihan Zentalis; and has provided research support to Janssen. MRS declares research funding to institution from ALX Oncology, Astex, Incyte, Takeda, and TG Therapeutics; consultancy fees from AbbVie, Bristol Myers Squibb, CTI BioPharma, Forma, Geron, GlaxoSmithKline, Karyopharm, Rigel, Ryvu, Taiho, and Treadwell; stock or stock options in Empath Bioscience, Karyopharm, and Ryvu; and medical writing support for this work from Kura Oncology. EAG declares Honoraria from AAMDS, MedscapeLive, MediCom Worldwide, MJH Health, ASH, MDS International Foundation, Physicians Educational Resource. Consulting from Abbvie, Alexion Pharmaceuticals, Apellis Pharmaceuticals, Takeda Oncology, Astex Pharmaceuticals/Taiho Oncology, Alexion/AstraZeneca Rare disease, Celgene/Bristol-Myers Squibb, CTI Biopharma, Novartis, Partner Therapeutics, Picnic Health, Servier. Research Funding: Alexion Pharmaceuticals, Apellis, Astex/Otsuka Pharmaceuticals/Taiho Oncology, Blueprint Medicines, Celldex Pharmaceuticals, Genentech Inc, NextCure, Inc. JMcC reported receipt of personal fees from BMS, Takeda, Blueprint Medicine, PharmaEssentia, CTI, GSK, Incyte, Amgen, and Jazz Pharmaceuticals. OO reports consulting fees from AbbVie, Blueprint Medicines, Bristol Myers Squibb, CTI, Impact Biomedicines, Kymera, Novartis, SERVIER, Taiho Pharmaceutical, and Treadwell Therapeutics; and received research funding (to institution) from AbbVie, Agios, Aprea AB, Astex Pharmaceuticals, AstraZeneca, Bristol Myers Squibb, Celgene, CTI BioPharma Corp, Daiichi Sankyo, Incyte, Janssen Oncology, Kartos Therapeutics, Loxo, Novartis, NS Pharma, and OncoTherapy Science. AO, HK, and MA are/were employed by Astex/Taiho Oncology. HMK has received research funding from AbbVie, Amgen, Ascentage Pharma, BMS, Daiichi Sankyo, ImmunoGen, Jazz Pharmaceuticals, and Novartis as well as honoraria from AbbVie, Amgen, Amphista Therapeutics, Ascentage Pharma, Astellas Pharma, Biologix, Curis, Ipsen, KAHR, Novartis, Pfizer, Precision Biosciences, Shenzhen TargetRx, and Takeda Oncology. Guillermo Garcia-Manero declares support from and an advisory role with Celgene Corporation, Astex, and Amphivena, and grant/research support 15 from Helsinn, Novartis, AbbVie, Onconova, H3 Biomedicine, and Merck. All other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1. Patient disposition in 3 clinical trials.
aCML atypical chronic myelocytic leukemia.
Fig. 2
Fig. 2. Genetic characteristics of the matched cohorts.
A Frequency of mutations and cytogenetic findings in each matched cohort. B Distribution of patients according to the IPSS-M score in each matched cohort. L low, ML moderate low, M moderate high, H high, VH very high.
Fig. 3
Fig. 3. Survival analysis.
A OS of patients in the DEC-C and DEC-C-Ven cohorts. B EFS of patients in the DEC-C and DEC-C-Ven cohorts. C Survival scatterplot. Each point represents 1 patient, localized according to their OS and EFS durations. Crossed points represent deceased patients. D 95% CI of death vs AML progression.
Fig. 4
Fig. 4. Volcano plot representing the hazard ratio for OS and EFS, along with the P value of each univariate analysis (represented as the −Log10 of the P value).
Dashed line represents P = 0.05. Point size is scaled to the frequency of each characteristic.
See this image and copyright information in PMC

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