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Review
. 2023 Sep;98(9):1383-1393.
doi: 10.1002/ajh.26997. Epub 2023 Jun 19.

Evolving trends and outcomes in older patients with acute myeloid leukemia including allogeneic stem cell transplantation

Alexandre Bazinet  1 , Hagop Kantarjian  1 , Naszrin Arani  2 , Uday Popat  3 , Alex Bataller  1 , Koji Sasaki  1 , Courtney D DiNardo  1 , Naval Daver  1 , Musa Yilmaz  1 , Hussein A Abbas  1   4 , Nicholas J Short  1 , Ghayas Issa  1 , Elias Jabbour  1 , Sherry A Pierce  1 , Julianne Chen  3 , Ricky Garcia  3 , Marina Konopleva  1 , Guillermo Garcia-Manero  1 , Amin Alousi  3 , Elizabeth J Shpall  3 , Richard E Champlin  3 , Gautam Borthakur  1 , Farhad Ravandi  1 , Tapan Kadia  1
Affiliations
Review

Evolving trends and outcomes in older patients with acute myeloid leukemia including allogeneic stem cell transplantation

Alexandre Bazinet et al. Am J Hematol. 2023 Sep.

Abstract

Outcomes in older patients with acute myeloid leukemia (AML) have historically been poor. Given advances in low-intensity therapy (LIT) and stem cell transplantation (SCT), we performed a retrospective single-center study to evaluate the contemporary outcomes of this population. We reviewed all patients ≥60 years with newly diagnosed AML between 2012 and 2021 and analyzed treatment and SCT-related trends and outcomes. We identified 1073 patients with a median age of 71 years. Adverse clinical and cytomolecular findings were frequent within this cohort. In total, 16% of patients were treated with intensive chemotherapy, 51% with LIT alone, and 32% with LIT plus venetoclax. The composite complete remission rate with LIT plus venetoclax was 72%, which was higher than with LIT alone (48%, p < .0001) and comparable to intensive chemotherapy (74%, p = .6). The median overall survival (OS) with intensive chemotherapy, LIT, and LIT plus venetoclax was 20.1, 8.9, and 12.1 months, respectively. 18% of patients received SCT. SCT rates were 37%, 10%, and 22% in patients treated with intensive chemotherapy, LIT, and LIT plus venetoclax, respectively. The 2-year OS, relapse-free survival (RFS), cumulative incidence (CI) of relapse, and CI of treatment-related mortality with frontline SCT (n = 139) were 59%, 52%, 27%, and 22%, respectively. By landmark analysis, patients undergoing frontline SCT had superior OS (median 39.6 vs. 21.4 months, p < .0001) and RFS (30.9 vs. 12.1 months, p < .0001) compared with responding patients who did not. Outcomes in older patients with AML are improving with more effective LIT. Measures should be pursued to increase access to SCT in older patients.

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Conflict of interest statement

Conflict of interest disclosure: H.K. declares research funding from Abbvie, Amgen, Ascentage, BMS, Daiichi Sankyo, Immunogen, Jazz Pharmaceuticals, Novartis, and honoraria from Abbvie, Amgen, Amphista, Ascentage, Astellas, Biologix, Curis, Ipsen Biopharmaceuticals, KAHR Medical, Novartis, Pfizer, Precision Biosciences, Shenzhen Target Rx, Takeda. U.P. declares research funding from Bayer, Incyte, Novartis, Abbvie. K.S. declares research funding from Novartis, consultancy from Novartis, honoraria from Otsuka Pharmaceuticals, and membership on an entity’s Board of Directors or advisory committees from Novartis, Pfizer, Daiichi-Sankyo. C.D.D. declares membership on an entity’s Board of Directors or advisory committees from GenMab, GlaxoSmithKline, Kura, Notable Labs, honoraria from Kura, Astellas, Bluebird Bio, Bristol Myers Squibb, Foghorn, ImmuneOnc, Novartis, Takeda, Gilead, Jazz Pharmaceuticals, current holder of stock options in a privately-held company from Notable Labs, consultancy from Abbvie, Servier, and research funding from Servier, Bristol Myers Squibb, Foghorn, ImmuneOnc, LOXO, Astex, Cleave, Forma. N.D. declares research funding from Astellas, AbbVie, Genentech, Daiichi-Sankyo, Gilead, Immunogen, Pfizer, Bristol Myers Squibb, Trovagene, Servier, Novimmune, Incyte, Hanmi, Fate, Amgen, Kite, Novartis, Astex, KAHR, Shattuck, Sobi, Glycomimetics, Trillium, advisory role from Astellas, AbbVie, Genentech, Daiichi-Sankyo, Novartis, Jazz, Amgen, Servier, Karyopharm, Trovagene, Trillium, Syndax, Gilead, Pfizer, Bristol Myers Squibb, Kite, Actinium, Arog, Immunogen, Arcellx, Shattuck, data monitoring committee member from Kartos, Jazz Pharmaceuticals, consultancy and membership on an entity’s Board of Directors or advisory committees from Agios, Celgene, SOBI, STAR Therapeutics, and research funding from Karyopham Therapeutics, Newave Pharmaceutical. M.Y. declares research funding from Daiichi-Sankyo, Pfizer. N.J.S. declares consultancy from Takeda Oncology, AstraZeneca, Amgen, Novartis, Pfizer, research funding from Takeda Oncology, Astellas, Stemline Therapeutics, and honoraria from Amgen. G.I. declares consultancy from Novartis, Kura Oncology, Nuprobe, and research funding from Celgene, Kura Oncology, Syndax, Merck, Cullinan, and Novartis. E.J. declares research funding from Amgen, Pfizer, Abbvie, Adaptive Biotechnologies, Astex, Ascentage, and consultancy from Amgen, Pfizer, Abbvie, Takeda, Adaptive Biotechnologies, Astex, Ascentage, Genentech, Novartis, BMS, Jazz Pharmaceuticals, Hikma Pharmaceuticals, Incyte. M.K. declares research funding from Abbvie, Genentech, F. Hoffman La Roche, Stemline Therapeutics, Forty-Seven, Eli Lilly, Cellectis, Calithera, Ablynx, Agios, Ascentage, AstraZeneca, Rafael Pharmaceuticals, Sanofi, Novartis, consultancy from Abbvie, Genentech, F. Hoffman La Roche, Stemline Therapeutics, Amgen, Forty-Seven, Kisoji, Janssen, Eli Lilly, Cellectis, honoraria from F. Hoffman La Roche, Forty-Seven, Kisoji, membership on an entity’s Board of Directors or advisory committees from F. Hoffman La Roche, Stemline Therapeutics, Janssen, current equity holder in private company from Reata Pharmaceuticals, and patents & royalties from Reata Pharmaceuticals, Eli Lilly, Novartis. G.G.-M. declares research funding from Astex Pharmaceuticals, Novartis, Abbvie, BMS, Genentech, Aprea Therapeutics, Curis, Gilead Sciences, consultancy from Astex Pharmaceuticals, Acceleron Pharma, BMS, and honoraria from Astex Pharmaceuticals, Acceleron Pharma, Abbvie, Novartis, Gilead Sciences, Curis, Genentech, BMS. A.A. declares honoraria from Incyte, Mallinckrodt, Sanofi/Kadmon, research funding from Incyte, and consultancy from Genentech, Prolacta. E.J.S. declares honoraria from Bayer, license agreements from Affimed, patents and royalties from Takeda, and consultancy from Navan, Fibroblasts and FibroBiologics, NY Blood Center, Adaptimmune, Axio. R.E.C. declares consultancy from Actinium, Kadmon, Johnson & Johnson, Omeros, data monitoring committee member from General Oncology, Bluebird, and research funding from Cell Source Inc. G.B. declares research funding from Astex, Ryvu Therapeutics, PTC Therapeutics, membership on an entity’s Board of Directors or advisory committees from Pacyclex, Novartis, Cytomx, Bio Ascend, and consultancy from Catamaran Bio, Abbvie, PPD Development, Protagonist Therapeutics, Janssen. F.R. declares research funding from Amgen, Astex/Taiho, BMS/Celgene, Syos, Abbvie, Prelude, Xencor, Astellas, Biomea Fusion, Inc., honoraria from Amgen, BMS/Celgene, Syos, Abbvie, Astellas, membership on an entity’s Board of Directors or advisory committees from Astex/Taiho, consultancy from BMS/Celgene, Syos, Novartis, Abbvie, AstraZeneca, Astellas. T.K. declares consultancy from Abbvie, Agios, BMS, Genentech, Jazz Pharmaceuticals, Novartis, Servier, PinotBio, research funding from Abbvie, BMS, Genentech, Jazz Pharmaceuticals, Pfizer, Cellenkos, Ascentage, GenFleet, Astellas, AstraZeneca, Amgen, Cyclacel Pharmaceuticals, Delta-Fly Pharma, Iterion, Glycomimetics, Regeneron, and honoraria from Astex. The remaining authors declared no competing interests.

Figures

Figure 1:
Figure 1:. Overall survival and relapse-free survival
(A) Overall survival stratified by frontline treatment regimen for the full cohort (n=1073). (B) Overall survival stratified by time of treatment initiation for the full cohort (n=1073). Venetoclax use became widespread from 2018 onwards. (C) Relapse-free survival stratified by frontline treatment regimen for patients achieving CR/CRi (n=643). (D) Relapse-free survival stratified by time of treatment initiation for patients achieving CR/CRi (n=643). Abbreviations: CR, complete remission; CRi, complete remission with incomplete count recovery; INT, intensive chemotherapy; LIT, low-intensity therapy; VEN, venetoclax.
Figure 2:
Figure 2:. Trends and outcomes of the patients undergoing allogeneic hematopoietic stem cell transplantation, including landmark analysis compared to non-transplanted controls
(A) Rate of referral to the SCT service in older patients with newly diagnosed AML, stratified by year of treatment initiation. (B) Rate of SCT completion (stem cells infused) in older patients with newly diagnosed AML, stratified by year of treatment initiation. (C) Overall survival from SCT day 0 in older patient with AML undergoing frontline SCT (n=139), stratified by age at the time of SCT. (D) Relapse-free survival from SCT day 0 in older patient with AML undergoing frontline SCT (n=139), stratified by age at the time of SCT. (E) CI of TRM from SCT day 0 in older patient with AML undergoing frontline SCT (n=139), stratified by age at the time of SCT. (F) CI of relapse from SCT day 0 in older patient with AML undergoing frontline SCT (n=139), stratified by age at the time of SCT. (G) Landmark analysis for overall survival stratified by frontline SCT versus no frontline SCT. (H) Landmark analysis for relapse-free survival stratified by frontline SCT versus no frontline SCT. Abbreviations: AML, acute myeloid leukemia; CI, cumulative incidence; SCT, allogeneic hematopoietic stem cell transplantation; TRM, treatment-related mortality.
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References

    1. Howlader N, Noone A, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2018. https://seer.cancer.gov/csr/1975_2018/. Accessed 5 January 2023.
    1. Appelbaum FR, Gundacker H, Head DR, et al. Age and acute myeloid leukemia. Blood 2006;107(9):3481–5. - PMC - PubMed
    1. Burnett AK, Milligan D, Prentice AG, et al. A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer 2007;109(6):1114–24. - PubMed
    1. Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood 2015;126(3):291–9. - PMC - PubMed
    1. Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol 2012;30(21):2670–7. - PMC - PubMed

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