Venetoclax Combined With Low-Dose Cytarabine for Previously Untreated Patients With Acute Myeloid Leukemia: Results From a Phase Ib/II Study
Open accessAbstract
PURPOSE: Effective treatment options are limited for patients with acute myeloid leukemia (AML) who cannot tolerate intensive chemotherapy. An international phase Ib/II study evaluated the safety and preliminary efficacy of venetoclax, a selective B-cell leukemia/lymphoma-2 inhibitor, together with low-dose cytarabine (LDAC) in older adults with AML. PATIENTS AND METHODS: Adults 60 years or older with previously untreated AML ineligible for intensive chemotherapy were enrolled. Prior treatment of myelodysplastic syndrome, including hypomethylating agents (HMA), was permitted. Eighty-two patients were treated at the recommended phase II dose: venetoclax 600 mg per day orally in 28-day cycles, with LDAC (20 mg/m 2 per day) administered subcutaneously on days 1 to 10. Key end points were tolerability, safety, response rates, duration of response (DOR), and overall survival (OS). RESULTS: Median age was 74 years (range, 63 to 90 years), 49% had secondary AML, 29% had prior HMA treatment, and 32% had poor-risk cytogenetic features. Common grade 3 or greater adverse events were febrile neutropenia (42%), thrombocytopenia (38%), and WBC count decreased (34%). Early (30-day) mortality was 6%. Fifty-four percent achieved complete remission (CR)/CR with incomplete blood count recovery (median time to first response, 1.4 months). The median OS was 10.1 months (95% CI, 5.7 to 14.2), and median DOR was 8.1 months (95% CI, 5.3 to 14.9 months). Among patients without prior HMA exposure, CR/CR with incomplete blood count recovery was achieved in 62%, median DOR was 14.8 months (95% CI, 5.5 months to not reached), and median OS was 13.5 months (95% CI, 7.0 to 18.4 months). CONCLUSION: Venetoclax plus LDAC has a manageable safety profile, producing rapid and durable remissions in older adults with AML ineligible for intensive chemotherapy. High remission rate and low early mortality combined with rapid and durable remission make venetoclax and LDAC an attractive and novel treatment for older adults not suitable for intensive chemotherapy.
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Historical outcomes with HMA treatment, including azacitidine or low-dose cytarabine administered with venetoclax, had median overall survival of 7.2 and 3.7 months, respectively.
“These findings compare favourably to historical outcomes with HMA treatment, including azacitidine or low-dose cytarabine administered with venetoclax where median OS was 7.2 and 3.7 months, respectively.32,33”
From Eprenetapopt (APR-246) and Azacitidine in <i>TP53</i> -Mutant Myelodysplastic Syndromes (2021) · cites this paper as [33]
The Results > Efficacy section (page unavailable) reports median overall survival of 10.1 months for patients receiving venetoclax plus low-dose cytarabine, not the claimed 3.7 months. The Discussion compares that regimen with azacitidine monotherapy; it does not report 7.2 months for azacitidine plus venetoclax. (LLM, conf=0.90)
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Cites
Vardiman, J., Thiele, J., Arber, D., Brunning, R., Borowitz, M., Porwit, A., Harris, N., Beau, M. L. L., Hellström-Lindberg, E., Tefferi, A., et al. (2009) · Blood · doi:10.1182/blood-2009-03-209262 · Cited by 4,837 · see citing works
Genomic classification and prognosis in acute myeloid leukemia
Papaemmanuil, E., Gerstung, M., Bullinger, L., Gaidzik, V. I., Paschka, P., Roberts, N. D., Potter, N. E., Heuser, M., Thol, F., Bolli, N., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1516192 · Cited by 4,350 · see citing works
Cheson, B. D., Bennett, J. M., Kopecky, K. J., Büchner, T., Willman, C. L., Estey, E. H., Schiffer, C. A., Döhner, H., Tallman, M. S., Lister, T. A., et al. (2003) · Journal of Clinical Oncology · doi:10.1200/jco.2003.04.036 · Cited by 2,686 · see citing works
Creutzig, U., & Kaspers, G. J. L. (2004) · Journal of Clinical Oncology · doi:10.1200/jco.2004.99.116 · Cited by 2,137 · see citing works
Targeting BCL2 with Venetoclax in Relapsed Chronic Lymphocytic Leukemia
Roberts, A. W., Davids, M. S., Pagel, J. M., Kahl, B. S., Puvvada, S. D., Gerecitano, J. F., Kipps, T. J., Anderson, M. A., Brown, J. R., Gressick, L. A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1513257 · Cited by 1,901 · see citing works
Self-citationLagadinou, E. D., Sach, A., Callahan, K. P., Rossi, R. M., Neering, S. J., Minhajuddin, M., Ashton, J. M., Pei, S., Grose, V., O’Dwyer, K. M., et al. (2013) · Cell stem cell · doi:10.1016/j.stem.2012.12.013 · Cited by 1,410 · see citing works
Age and acute myeloid leukemia
Appelbaum, F. R., Gundacker, H. M., Head, D. R., Slovak, M. L., Willman, C. L., Godwin, J. E., Anderson, J. E., & Petersdorf, S. H. (2006) · Blood · doi:10.1182/blood-2005-09-3724 · Cited by 1,352 · see citing works
Kantarjian, H. M., Thomas, X., Dmoszyńska, A., Wierzbowska, A., Mazur, G. J., Mayer, J., Gau, J., Chou, W., Buckstein, R. J., Čermák, J., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.38.9429 · Cited by 1,170 · see citing works
Dombret, H., Seymour, J. F., Butrym, A., Wierzbowska, A., Selleslag, D., Jang, J. H., Kumar, R., Cavenagh, J., Schuh, A. C., Candoni, A., et al. (2015) · Blood · doi:10.1182/blood-2015-01-621664 · Cited by 1,165 · see citing works
Konopleva, M. Y., Pollyea, D. A., Potluri, J., Chyla, B., Hogdal, L. J., Busman, T. A., McKeegan, E. M., Salem, A. H., Zhu, M., Ricker, J. L., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0313 · Cited by 1,067 · see citing works
Self-citationHoward, S. C., Jones, D. P., & Pui, C.-H. (2011) · New England Journal of Medicine · doi:10.1056/nejmra0904569 · Cited by 1,044 · see citing works
Lancet, J. E., Uy, G. L., Cortes, J. E., Newell, L. F., Lin, T. L., Ritchie, E. K., Stuart, R. K., Strickland, S. A., Hogge, D. E., Solomon, S. R., et al. (2018) · Journal of Clinical Oncology · doi:10.1200/jco.2017.77.6112 · Cited by 1,031 · see citing works
Self-citationJuliusson, G., Antunović, P., Derolf, Å. R., Lehmann, S., Möllgård, L., Stockelberg, D., Tidefelt, U., Wåhlin, A., & Höglund, M. (2008) · Blood · doi:10.1182/blood-2008-07-172007 · Cited by 991 · see citing works
Venetoclax-Rituximab in Relapsed or Refractory Chronic Lymphocytic Leukemia
Seymour, J. F., Kipps, T. J., Eichhorst, B., Hillmen, P., D’Rozario, J., Assouline, S., Owen, C., Gerecitano, J., Robak, T., De la Serna, J., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmoa1713976 · Cited by 940 · see citing works
Self-citationStilgenbauer, S., Eichhorst, B. F., Schetelig, J., Coutre, S. E., Seymour, J. F., Munir, T., Puvvada, S. D., Wendtner, C., Roberts, A. W., Jurczak, W. J., et al. (2016) · The Lancet Oncology · doi:10.1016/s1470-2045(16)30019-5 · Cited by 809 · see citing works
Self-citationDinardo, C. D., Pratz, K. W., Letai, A. G., Jonas, B. A., Wei, A. H., Thirman, M. J., Arellano, M. L., Frattini, M. G., Kantarjian, H. M., Popovic, R., et al. (2018) · The Lancet Oncology · doi:10.1016/s1470-2045(18)30010-x · Cited by 723 · see citing works
Self-citationBurnett, A. K., Milligan, D., Prentice, A. G., Goldstone, A. H., McMullin, M. F., Hills, R. K., & Wheatley, K. (2007) · Cancer · doi:10.1002/cncr.22496 · Cited by 619 · see citing works
Kantarjian, H. M., O'Brien, S. M., Cortes, J. E., Giles, F. J., Faderl, S. H., Jabbour, E. J., Garcia‐Manero, G., Wierda, W. G., Pierce, S. A., Shan, J., et al. (2006) · Cancer · doi:10.1002/cncr.21723 · Cited by 608 · see citing works
Breems, D. A., van Putten, W. L. J., de Greef, G. E., van Zelderen‐Bhola, S. L., Gerssen‐Schoorl, K. B. J., Mellink, C. H. M., Nieuwint, A. W. M., Jotterand, M., Hagemeijer, A., Beverloo, H. B., et al. (2008) · Journal of Clinical Oncology · doi:10.1200/jco.2008.16.0259 · Cited by 576 · see citing works
Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma
Kumar, S. K., Kaufman, J. L., Gasparetto, C., Mikhael, J. R., Vij, R., Pegourié, B., Benboubker, L., Facon, T. T. F., Amiot, M., Moreau, P., et al. (2017) · Blood · doi:10.1182/blood-2017-06-788786 · Cited by 526 · see citing works
Self-citationOutcome of High-Risk Myelodysplastic Syndrome After Azacitidine Treatment Failure
Prébet, T., Gore, S. D., Esterni, B., Gardin, C., Itzykson, R., Thepot, S., Dreyfus, F., Rauzy, O. B., Recher, C., Adès, L., et al. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2011.35.8135 · Cited by 475 · see citing works
Cashen, A. F., Schiller, G. J., O'Donnell, M. R., & DiPersio, J. F. (2009) · Journal of Clinical Oncology · doi:10.1200/jco.2009.23.9178 · Cited by 464 · see citing works
Survival for older patients with acute myeloid leukemia: a population-based study
Oran, B., & Weisdorf, D. J. (2012) · Haematologica · doi:10.3324/haematol.2012.066100 · Cited by 423 · see citing works
Kantarjian, H. M., Ravandi, F., O'Brien, S. M., Cortes, J. E., Faderl, S. H., Garcia‐Manero, G., Jabbour, E. J., Wierda, W. G., Kadia, T. M., Pierce, S. A., et al. (2010) · Blood · doi:10.1182/blood-2010-03-276485 · Cited by 403 · see citing works
Amadori, S., Suciu, S., Selleslag, D., Aversa, F., Gaïdano, G., Musso, M., Annino, L., Venditti, A., Voso, M. T., Mazzone, C., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.64.0060 · Cited by 362 · see citing works
Poeta, G. D., Venditti, A., Principe, M. I. D., Maurillo, L., Buccisano, F., Tamburini, A., Cox, M. C., Franchi, A., Bruno, A., Mazzone, C., et al. (2003) · Blood · doi:10.1182/blood-2002-06-1714 · Cited by 339 · see citing works
Moreau, P., Chanan-Khan, A. A., Roberts, A. W., Agarwal, A. B., Facon, T. T. F., Kumar, S. K., Touzeau, C., Punnoose, E. A., Cordero, J., Munasinghe, W. P., et al. (2017) · Blood · doi:10.1182/blood-2017-06-788323 · Cited by 273 · see citing works
Self-citationNiu, X., Zhao, J., Ma, J., Xie, C., Edwards, H. J., Wang, G., Caldwell, J. T., Xiang, S., Zhang, X. M., Chu, R. L., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-3057 · Cited by 249 · see citing works
Agarwal, S. K., Dinardo, C. D., Potluri, J., Dunbar, M., Kantarjian, H. M., Humerickhouse, R. A., Wong, S. L., Menon, R. M., Konopleva, M. Y., & Salem, A. H. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2017.01.003 · Cited by 238 · see citing works
Self-citationDöhner, H., Lübbert, M., Fiedler, W., Fouillard, L., Haaland, A. K., Brandwein, J. M., Leprêtre, S., Reman, O., Turlure, P., Ottmann, O. G., et al. (2014) · Blood · doi:10.1182/blood-2014-03-560557 · Cited by 233 · see citing works
Self-citationJabbour, E. J., Kantarjian, H. M., O'Brien, S. M., Cortes, J. E., Giles, F. J., Faderl, S. H., Garcia‐Manero, G., Wierda, W. G., Pierce, S. A., Shan, J., et al. (2005) · Blood · doi:10.1182/blood.v106.11.1846.1846 · Cited by 183 · see citing works
Gardin, C., Turlure, P., Fagot, T., Thomas, X., Terré, C., Contentin, N., Raffoux, E., de Botton, S., Pautas, C., Reman, O., et al. (2007) · Blood · doi:10.1182/blood-2007-02-069666 · Cited by 174 · see citing works
Genomic Classification in Acute Myeloid Leukemia
Papaemmanuil, E., Döhner, H., & Campbell, P. J. (2016) · New England Journal of Medicine · doi:10.1056/nejmc1608739 · Cited by 166 · see citing works
Enhancing venetoclax activity in acute myeloid leukemia by co-targeting MCL1
Teh, T.-C., Nguyen, N.-Y., Moujalled, D. M., Segal, D., Pomilio, G., Rijal, S., Jabbour, A. M., Cummins, K. D., Lackovic, K., Blombery, P. A., et al. (2017) · Leukemia · doi:10.1038/leu.2017.243 · Cited by 161 · see citing works
Self-citationBogenberger, J. M., Delman, D., Hansen, N., Valdez, R., Fauble, V. D. S., Mesa, R. A., & Tibes, R. (2014) · Leukemia & lymphoma/Leukemia and lymphoma · doi:10.3109/10428194.2014.910657 · Cited by 152 · see citing works
Chyla, B., Daver, N. G., Doyle, K. J., McKeegan, E. M., Huang, X., Ruvolo, V. R., Wang, Z., Chen, K., Souers, A. J., Leverson, J. D., et al. (2018) · American Journal of Hematology · doi:10.1002/ajh.25146 · Cited by 148 · see citing works
Self-citationVenetoclax and obinutuzumab in chronic lymphocytic leukemia
Fischer, K., Al‐Sawaf, O., Fink, A., Dixon, M., Bahlo, J., Warburton, S., Kipps, T. J., Weinkove, R., Robinson, S., Seiler, T., et al. (2017) · Blood · doi:10.1182/blood-2017-01-761973 · Cited by 119 · see citing works
Self-citationAgarwal, S. K., Salem, A. H., Danilov, A. V., Hu, B., Puvvada, S. D., Gutierrez, M. E., Chien, D. C., Lewis, L. D., & Wong, S. L. (2016) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.13175 · Cited by 107 · see citing works
Self-citationThe role of hypomethylating agents in the treatment of elderly patients with AML
Al‐Ali, H. K., Jaekel, N., & Niederwieser, D. W. (2013) · Journal of Geriatric Oncology · doi:10.1016/j.jgo.2013.08.004 · Cited by 57 · see citing works
Ma, E., Bonthapally, V., Chawla, A., Lefèbvre, P., Swords, R. T., Lafeuille, M.-H., Fortier, J., Émond, B., Duh, M. S., & Dezube, B. J. (2016) · Clinical Lymphoma Myeloma & Leukemia · doi:10.1016/j.clml.2016.08.006 · Cited by 42 · see citing works
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- [4]Dennis M, Hills RK, Russell NH, et al: An evaluation of 17 years of low dose cytarabine as therapy for AML patients not fit for intensive treatment, including patients with adverse cytogenetics, shows improving survival, potential underutilisation and highlights the need for new therapy. Blood 2017; 130:3874
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Eprenetapopt (APR-246) and Azacitidine in <i>TP53</i> -Mutant Myelodysplastic Syndromes
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“Complete 18 (33) [21 to 47] 15 (38) [23 to 54] 3 (27) [6 to 61]”
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- Authors
- Wei, A. H., Strickland, S. A., Hou, J.-Z., Fiedler, W., Lin, T. L., Walter, R. B., Enjeti, A., Tiong, I. S., Savona, M., Lee, S., Chyla, B., Popovic, R., Salem, A. H., Agarwal, S., Xu, T., Fakouhi, K. M., Humerickhouse, R., Hong, W.-J., Hayslip, J., & Roboz, G. J.
- Affiliations
- The Alfred Hospital (AU)
- Vanderbilt University (US)
- UPMC Hillman Cancer Center (US)
- University Medical Center Hamburg-Eppendorf (DE)
- University of Kansas Medical Center (US)
- University of Washington (US)
- Calvary Mater Newcastle Hospital (AU)
- Weill Cornell Medical College, New York, NY
- AbbVie (United States) (US)
- Ain Shams University (EG)
- Genentech (US)
- Weill Cornell Medicine (US)
- Corresponding author
- Wei, Andrew H.
- ORCID
- Venue
- Journal of Clinical Oncology
- Published
- 2019-05-20
- Volume
- 37
- Issue
- 15
- Pages
- 1277-1284
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- PMC
- PMC6524989
- OpenAlex
- W2922692686
- Cited by
- 692
- References
- 40
- Citations by year
- 2026: 33 · 2025: 43 · 2024: 85 · 2023: 96 · 2022: 91 · 2021: 123 · 2020: 164 · 2019: 55
- FWCI
- 77.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Journal of Clinical Oncology (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Monash University Research Portal (Monash University) (acceptedVersion, cc-by-nc-nd)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by-nc-nd)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Funders
- Amgen
- Pfizer
- AstraZeneca
- Sanofi
- Gilead Sciences
- Ariad Pharmaceuticals
- Alexion Pharmaceuticals
- Celgene
- Karyopharm Therapeutics
- Array BioPharma
- Helsinn
- Actinium Pharmaceuticals
- Jazz Pharmaceuticals
- TG Therapeutics
- Astex Pharmaceuticals
- Clovis Oncology
- LAM Therapeutics
- Sunesis
- MEI Pharma
- Agios Pharmaceuticals
- Arog Pharmaceuticals
- Mateon Therapeutics
- Incyte
- Celltrion
- Argenx
- Eisai
- Astellas Pharma
- Otsuka Pharmaceutical
- Ono Pharmaceutical
- Genentech
- Helsinn Therapeutics
- Kite Pharma
- Pharmacyclics
- Celator Pharmaceuticals
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
- Health Sciences › Medicine › Pharmacology › Flavonoids in Medical Research
- Keywords
- venetoclax, low-dose cytarabine, acute myeloid leukemia, older adults, BCL-2 inhibitor, hypomethylating agents, complete remission, overall survival, duration of response, febrile neutropenia, myelodysplastic syndrome, combination therapy, safety and tolerability, secondary acute myeloid leukemia, poor-risk cytogenetics
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols, Cytarabine, Female, Humans, Male, Middle Aged, Mutation, Sulfonamides, Leukemia, Myeloid, Acute, Bridged Bicyclo Compounds, Heterocyclic
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