Optimizing Treatment Options for Newly Diagnosed Acute Myeloid Leukemia in Older Patients with Comorbidities
Abstract
:Simple Summary
Abstract
1. Introduction
2. Risk Factors for Patients with AML Undergoing Intensive Chemotherapy
3. DNA Methyltransferase Inhibitors and Venetoclax for AML
4. Intensive Chemotherapy versus Low-Intensity Chemotherapy
5. Summary
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Jabbour, E.; Short, N.J.; Ravandi, F.; Huang, X.; Xiao, L.; Garcia-Manero, G.; Plunkett, W.; Gandhi, V.; Sasaki, K.; Pemmaraju, N.; et al. A randomized phase 2 study of idarubicin and cytarabine with clofarabine or fludarabine in patients with newly diagnosed acute myeloid leukemia. Cancer 2017, 123, 4430–4439. [Google Scholar] [CrossRef] [PubMed]
- Short, N.J.; Kantarjian, H.; Ravandi, F.; Huang, X.; Xiao, L.; Garcia-Manero, G.; Plunkett, W.; Gandhi, V.; Sasaki, K.; Pemmaraju, N.; et al. A phase I/II randomized trial of clofarabine or fludarabine added to idarubicin and cytarabine for adults with relapsed or refractory acute myeloid leukemia. Leuk. Lymphoma 2017, 59, 813–820. [Google Scholar] [CrossRef] [PubMed]
- Morita, K.; Kantarjian, H.M.; Wang, F.; Yan, Y.; Bueso-Ramos, C.; Sasaki, K.; Issa, G.C.; Wang, S.; Jorgensen, J.; Song, X.; et al. Clearance of Somatic Mutations at Remission and the Risk of Relapse in Acute Myeloid Leukemia. J. Clin. Oncol. 2018, 36, 1788–1797. [Google Scholar] [CrossRef]
- Lachowiez, C.A.; Loghavi, S.; Kadia, T.M.; Daver, N.; Borthakur, G.; Pemmaraju, N.; Naqvi, K.; Alvarado, Y.; Yilmaz, M.; Short, N.; et al. Outcomes of older patients with NPM1-mutated AML: Current treatments and the promise of venetoclax-based regimens. Blood Adv. 2020, 4, 1311–1320. [Google Scholar] [CrossRef]
- Sasaki, K.; Kanagal-Shamanna, R.; Montalban-Bravo, G.; Assi, R.; Jabbour, E.; Ravandi, F.; Kadia, T.; Pierce, S.; Takahashi, K.; Gonzalez, G.N.; et al. Impact of the variant allele frequency of ASXL1, DNMT3A, JAK2, TET2, TP53, and NPM1 on the outcomes of patients with newly diagnosed acute myeloid leukemia. Cancer 2020, 126, 765–774. [Google Scholar] [CrossRef] [PubMed]
- Sasaki, K.; Kantarjian, H.M.; Kadia, T.; Patel, K.; Loghavi, S.; Garcia-Manero, G.; Jabbour, E.J.; DiNardo, C.; Pemmaraju, N.; Daver, N.; et al. Sorafenib plus intensive chemotherapy improves survival in patients with newly diagnosed, FLT3-internal tandem duplication mutation-positive acute myeloid leukemia. Cancer 2019, 125, 3755–3766. [Google Scholar] [CrossRef] [PubMed]
- Sasaki, K.; Ravandi, F.; Kadia, T.M.; DiNardo, C.D.; Short, N.J.; Borthakur, G.; Jabbour, E.; Kantarjian, H.M. De novo acute myeloid leukemia: A population-based study of outcome in the United States based on the Surveillance, Epidemiology, and End Results (SEER) database, 1980 to 2017. Cancer 2021, 127, 2049–2061. [Google Scholar] [CrossRef]
- Rausch, C.R.; DiNardo, C.D.; Maiti, A.; Jammal, N.J.; Kadia, T.M.; Marx, K.R.; Borthakur, G.; Savoy, J.M.; Pemmaraju, N.; DiPippo, A.J.; et al. Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia. Cancer 2021, 127, 2489–2499. [Google Scholar] [CrossRef]
- Maiti, A.; DiNardo, C.D.; Wang, S.A.; Jorgensen, J.; Kadia, T.M.; Daver, N.G.; Short, N.J.; Yilmaz, M.; Pemmaraju, N.; Borthakur, G.; et al. Prognostic value of measurable residual disease after venetoclax and decitabine in acute myeloid leukemia. Blood Adv. 2021, 5, 1876–1883. [Google Scholar] [CrossRef]
- Maiti, A.; Qiao, W.; Sasaki, K.; Ravandi, F.; Kadia, T.M.; Jabbour, E.J.; Daver, N.G.; Borthakur, G.; Garcia-Manero, G.; Pierce, S.A.; et al. Venetoclax with decitabine vs intensive chemotherapy in acute myeloid leukemia: A propensity score matched analysis stratified by risk of treatment-related mortality. Am. J. Hematol. 2020, 96, 282–291. [Google Scholar] [CrossRef]
- Reville, P.K.; Sasaki, K.; Kantarjian, H.M.; Daver, N.G.; Yilmaz, M.; Dinardo, C.D.; Short, N.J.; Borthakur, G.; Pemmaraju, N.; Mehta, R.S.; et al. Improved outcomes among newly diagnosed patients with FMS-like tyrosine kinase 3 internal tandem duplication mutated acute myeloid leukemia treated with contemporary therapy: Revisiting the European LeukemiaNet adverse risk classification. Am. J. Hematol. 2022, 97, 329–337. [Google Scholar] [CrossRef] [PubMed]
- Abbas, H.A.; Reville, P.K.; Geppner, A.; Rausch, C.R.; Pemmaraju, N.; Ohanian, M.; Sasaki, K.; Borthakur, G.; Daver, N.; DiNardo, C.; et al. Clinical and molecular characterization of myeloid sarcoma without medullary leukemia. Leuk. Lymphoma 2021, 62, 3402–3410. [Google Scholar] [CrossRef] [PubMed]
- Tanaka, T.; Morita, K.; Loghavi, S.; Wang, F.; Furudate, K.; Sasaki, Y.; Little, L.D.; Gumbs, C.E.; Matthews, J.; Daver, N.G.; et al. Clonal dynamics and clinical implications of postremission clonal hematopoiesis in acute myeloid leukemia. Blood 2021, 138, 1733–1739. [Google Scholar] [CrossRef]
- DiNardo, C.D.; Lachowiez, C.A.; Takahashi, K.; Loghavi, S.; Xiao, L.; Kadia, T.; Daver, N.; Adeoti, M.; Short, N.J.; Sasaki, K.; et al. Venetoclax Combined With FLAG-IDA Induction and Consolidation in Newly Diagnosed and Relapsed or Refractory Acute Myeloid Leukemia. J. Clin. Oncol. 2021, 39, 2768–2778. [Google Scholar] [CrossRef] [PubMed]
- Issa, G.C.; Bidikian, A.; Venugopal, S.; Konopleva, M.Y.; DiNardo, C.D.; Kadia, T.M.; Borthakur, G.; Jabbour, E.; Pemmaraju, N.; Yilmaz, M.; et al. Clinical outcomes associated with NPM1 mutations in patients with relapsed or refractory AML. Blood Adv. 2022, 7, 933–943. [Google Scholar] [CrossRef]
- Sasaki, K.; Ravandi, F.; Kadia, T.; DiNardo, C.; Borthakur, G.; Short, N.; Jain, N.; Daver, N.; Jabbour, E.; Garcia-Manero, G.; et al. Prediction of survival with intensive chemotherapy in acute myeloid leukemia. Am. J. Hematol. 2022, 97, 865–876. [Google Scholar] [CrossRef]
- Sasaki, K.; Jabbour, E.; Cortes, J.; Kadia, T.; Garcia-Manero, G.; Borthakur, G.; Jain, P.; Pierce, S.; Daver, N.; Takahashi, K.; et al. Outcome of Patients With Therapy-Related Acute Myeloid Leukemia With or Without a History of Myelodysplasia. Clin. Lymphoma Myeloma Leuk. 2016, 16, 616–624. [Google Scholar] [CrossRef]
- Abou Dalle, I.; Ghorab, A.; Patel, K.; Wang, X.; Hwang, H.; Cortes, J.; Issa, G.C.; Yalniz, F.; Sasaki, K.; Chihara, D.; et al. Impact of numerical variation, allele burden, mutation length and co-occurring mutations on the efficacy of tyrosine kinase inhibitors in newly diagnosed FLT3- mutant acute myeloid leukemia. Blood Cancer J. 2020, 10, 48. [Google Scholar] [CrossRef]
- Quesada, A.E.; Montalban-Bravo, G.; Luthra, R.; Patel, K.P.; Sasaki, K.; Bueso-Ramos, C.E.; Khoury, J.D.; Routbort, M.J.; Bassett, R.; Hidalgo-Lopez, J.E.; et al. Clinico-pathologic characteristics and outcomes of the World Health Organization (WHO) provisional entity de novo acute myeloid leukemia with mutated RUNX1. Mod. Pathol. 2020, 33, 1678–1689. [Google Scholar] [CrossRef]
- Montalban-Bravo, G.; Kanagal-Shamanna, R.; Class, C.A.; Sasaki, K.; Ravandi, F.; Cortes, J.E.; Daver, N.; Takahashi, K.; Short, N.J.; DiNardo, C.D.; et al. Outcomes of acute myeloid leukemia with myelodysplasia related changes depend on diagnostic criteria and therapy. Am. J. Hematol. 2020, 95, 612–622. [Google Scholar] [CrossRef]
- Yalniz, F.; Dalle, I.A.; Kantarjian, H.; Borthakur, G.; Kadia, T.; Patel, K.; Loghavi, S.; Garcia-Manero, G.; Sasaki, K.; Daver, N.; et al. Prognostic significance of baseline FLT3-ITD mutant allele level in acute myeloid leukemia treated with intensive chemotherapy with/without sorafenib. Am. J. Hematol. 2019, 94, 984–991. [Google Scholar] [CrossRef]
- Shoukier, M.; Kadia, T.; Konopleva, M.; Alotaibi, A.S.; Alfayez, M.; Loghavi, S.; Patel, K.P.; Kanagal-Shamanna, R.; Cortes, J.; Samra, B.; et al. Clinical characteristics and outcomes in patients with acute myeloid leukemia with concurrent FLT3 -ITD and IDH mutations. Cancer 2020, 127, 381–390. [Google Scholar] [CrossRef] [PubMed]
- Major, C.K.; Kantarjian, H.; Sasaki, K.; Borthakur, G.; Kadia, T.; Pemmaraju, N.; Dinardo, C.; Short, N.J.; Daver, N.; Jabbour, E.; et al. Survivorship in AML—A landmark analysis on the outcomes of acute myelogenous leukemia patients after maintaining complete remission for at least 3 years. Leuk. Lymphoma 2020, 61, 3120–3127. [Google Scholar] [CrossRef] [PubMed]
- Sasaki, K.; Ravandi, F.; Kadia, T.M.; Borthakur, G.; Short, N.J.; Jain, N.; Daver, N.G.; Jabbour, E.J.; Garcia-Manero, G.; Loghavi, S.; et al. Prediction of survival with lower intensity therapy among older patients with acute myeloid leukemia. Cancer 2023, 129, 1017–1029. [Google Scholar] [CrossRef]
- Kadia, T.M.; Cortes, J.; Ravandi, F.; Jabbour, E.; Konopleva, M.; Benton, C.B.; Burger, J.; Sasaki, K.; Borthakur, G.; DiNardo, C.D.; et al. Cladribine and low-dose cytarabine alternating with decitabine as front-line therapy for elderly patients with acute myeloid leukaemia: A phase 2 single-arm trial. Lancet Haematol. 2018, 5, e411–e421. [Google Scholar] [CrossRef]
- Chien, K.S.; Class, C.A.; Montalban-Bravo, G.; Wei, Y.; Sasaki, K.; Naqvi, K.; Ganan-Gomez, I.; Yang, H.; Soltysiak, K.A.; Kanagal-Shamanna, R.; et al. LILRB4 expression in chronic myelomonocytic leukemia and myelodysplastic syndrome based on response to hypomethylating agents. Leuk. Lymphoma 2020, 61, 1493–1499. [Google Scholar] [CrossRef] [PubMed]
- Maiti, A.; Franquiz, M.J.; Ravandi, F.; Cortes, J.E.; Jabbour, E.J.; Sasaki, K.; Marx, K.; Daver, N.G.; Kadia, T.M.; Konopleva, M.Y.; et al. Venetoclax and BCR-ABL Tyrosine Kinase Inhibitor Combinations: Outcome in Patients with Philadelphia Chromosome-Positive Advanced Myeloid Leukemias. Acta Haematol. 2020, 143, 567–573. [Google Scholar] [CrossRef]
- Lachowiez, C.A.; Loghavi, S.; Furudate, K.; Montalban-Bravo, G.; Maiti, A.; Kadia, T.; Daver, N.; Borthakur, G.; Pemmaraju, N.; Sasaki, K.; et al. Impact of splicing mutations in acute myeloid leukemia treated with hypomethylating agents combined with venetoclax. Blood Adv. 2021, 5, 2173–2183. [Google Scholar] [CrossRef]
- Dalle, I.A.; Paranal, R.; Zarka, J.; Paul, S.; Sasaki, K.; Li, W.; Ning, J.; Short, N.J.; Ohanian, M.; Cortes, J.E.; et al. Impact of luteinizing hormone suppression on hematopoietic recovery after intensive chemotherapy in patients with leukemia. Haematologica 2021, 106, 1097–1105. [Google Scholar] [CrossRef]
- Venugopal, S.; Shoukier, M.; Konopleva, M.; Dinardo, C.D.; Ravandi, F.; Short, N.J.; Andreeff, M.; Borthakur, G.; Daver, N.; Pemmaraju, N.; et al. Outcomes in patients with newly diagnosed TP53 -mutated acute myeloid leukemia with or without venetoclax-based therapy. Cancer 2021, 127, 3541–3551. [Google Scholar] [CrossRef]
- Kim, K.; Maiti, A.; Loghavi, S.; Pourebrahim, R.; Kadia, T.M.; Rausch, C.R.; Furudate, K.; Daver, N.G.; Alvarado, Y.; Ohanian, M.; et al. Outcomes of TP53 -mutant acute myeloid leukemia with decitabine and venetoclax. Cancer 2021, 127, 3772–3781. [Google Scholar] [CrossRef] [PubMed]
- Sasaki, K.; Kadia, T.; Begna, K.; DiNardo, C.D.; Borthakur, G.; Short, N.J.; Jain, N.; Daver, N.; Jabbour, E.; Garcia-Manero, G.; et al. Prediction of early (4-week) mortality in acute myeloid leukemia with intensive chemotherapy. Am. J. Hematol. 2021, 97, 68–78. [Google Scholar] [CrossRef]
- Bazinet, A.; Darbaniyan, F.; Kadia, T.M.; Venugopal, S.; Kanagal-Shamanna, R.; DiNardo, C.D.; Borthakur, G.; Jabbour, E.J.; Daver, N.G.; Pemmaraju, N.; et al. A retrospective study of cladribine and low-dose cytarabine–based regimens for the treatment of chronic myelomonocytic leukemia and secondary acute myeloid leukemia. Cancer 2022, 129, 560–568. [Google Scholar] [CrossRef] [PubMed]
- Lachowiez, C.A.; Reville, P.K.; Kantarjian, H.; Jabbour, E.; Borthakur, G.; Daver, N.; Issa, G.; Furudate, K.; Tanaka, T.; Pierce, S.; et al. Contemporary outcomes in IDH-mutated acute myeloid leukemia: The impact of co-occurring NPM1 mutations and venetoclax-based treatment. Am. J. Hematol. 2022, 97, 1443–1452. [Google Scholar] [CrossRef] [PubMed]
- Kantarjian, H.; Kadia, T.; DiNardo, C.; Daver, N.; Borthakur, G.; Jabbour, E.; Garcia-Manero, G.; Konopleva, M.; Ravandi, F. Acute myeloid leukemia: Current progress and future directions. Blood Cancer J. 2021, 11, 41. [Google Scholar] [CrossRef]
- Appelbaum, F.R.; Gundacker, H.; Head, D.R.; Slovak, M.L.; Willman, C.L.; Godwin, J.E.; Anderson, J.E.; Petersdorf, S.H. Age and acute myeloid leukemia. Blood 2006, 107, 3481–3485. [Google Scholar] [CrossRef] [PubMed]
- Löwenberg, B.; Ossenkoppele, G.J.; van Putten, W.; Schouten, H.C.; Graux, C.; Ferrant, A.; Sonneveld, P.; Maertens, J.; Jongen-Lavrencic, M.; von Lilienfeld-Toal, M.; et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N. Engl. J. Med. 2009, 361, 1235–1248. [Google Scholar] [CrossRef]
- Charlson, M.E.; Pompei, P.; Ales, K.L.; MacKenzie, C.R. A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J. Chronic Dis. 1987, 40, 373–383. [Google Scholar] [CrossRef]
- Kantarjian, H.; O’Brien, S.; Cortes, J.; Giles, F.; Faderl, S.; Jabbour, E.; Garcia-Manero, G.; Wierda, W.; Pierce, S.; Shan, J.; et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: Predictive prognostic models for outcome. Cancer 2006, 106, 1090–1098. [Google Scholar] [CrossRef]
- Kantarjian, H.; Ravandi, F.; O’Brien, S.; Cortes, J.; Faderl, S.; Garcia-Manero, G.; Jabbour, E.; Wierda, W.; Kadia, T.; Pierce, S.; et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood 2010, 116, 4422–4429. [Google Scholar] [CrossRef]
- Sorror, M.L.; Storer, B.E.; Fathi, A.T.; Gerds, A.; Medeiros, B.C.; Shami, P.; Brunner, A.M.; Sekeres, M.; Mukherjee, S.; Peña, E.; et al. Development and Validation of a Novel Acute Myeloid Leukemia–Composite Model to Estimate Risks of Mortality. JAMA Oncol. 2017, 3, 1675–1682. [Google Scholar] [CrossRef] [PubMed]
- Wheatley, K.; Brookes, C.L.; Howman, A.J.; Goldstone, A.H.; Milligan, D.W.; Prentice, A.G.; Moorman, A.V.; Burnett, A.K.; United Kingdom National Cancer Research Institute Haematological Oncology Clinical Studies Group and Acute Myeloid Leukaemia Subgroup. Prognostic factor analysis of the survival of elderly patients with AML in the MRC AML11 and LRF AML14 trials. Br. J. Haematol. 2009, 145, 598–605. [Google Scholar] [CrossRef] [PubMed]
- Krug, U.; Röllig, C.; Koschmieder, A.; Heinecke, A.; Sauerland, M.C.; Schaich, M.; Thiede, C.; Kramer, M.; Braess, J.; Spiekermann, K.; et al. Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: A web-based application for prediction of outcomes. Lancet 2010, 376, 2000–2008. [Google Scholar] [CrossRef] [PubMed]
- Walter, R.B.; Othus, M.; Borthakur, G.; Ravandi, F.; Cortes, J.; Pierce, S.A.; Appelbaum, F.R.; Kantarjian, H.A.; Estey, E.H. Prediction of Early Death After Induction Therapy for Newly Diagnosed Acute Myeloid Leukemia With Pretreatment Risk Scores: A Novel Paradigm for Treatment Assignment. J. Clin. Oncol. 2011, 29, 4417–4424. [Google Scholar] [CrossRef]
- Bérard, E.; Röllig, C.; Bertoli, S.; Pigneux, A.; Tavitian, S.; Kramer, M.; Serve, H.; Bornhäuser, M.; Platzbecker, U.; Müller-Tidow, C.; et al. A scoring system for AML patients aged 70 years or older, eligible for intensive chemotherapy: A study based on a large European data set using the DATAML, SAL, and PETHEMA registries. Blood Cancer J. 2022, 12, 107. [Google Scholar] [CrossRef] [PubMed]
- Fenaux, P.; Mufti, G.J.; Hellstrom-Lindberg, E.; Santini, V.; Finelli, C.; Giagounidis, A.; Schoch, R.; Gattermann, N.; Sanz, G.; List, A.; et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: A randomised, open-label, phase III study. Lancet Oncol. 2009, 10, 223–232. [Google Scholar] [CrossRef] [PubMed]
- Fenaux, P.; Mufti, G.J.; Hellström-Lindberg, E.; Santini, V.; Gattermann, N.; Germing, U.; Sanz, G.; List, A.F.; Gore, S.; Seymour, J.F.; et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia. J. Clin. Oncol. 2010, 28, 562–569. [Google Scholar] [CrossRef]
- 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. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood 2015, 126, 291–299. [Google Scholar] [CrossRef]
- Konopleva, M.; Pollyea, D.A.; Potluri, J.; Chyla, B.; Hogdal, L.; Busman, T.; McKeegan, E.; Salem, A.H.; Zhu, M.; Ricker, J.L.; et al. Efficacy and Biological Correlates of Response in a Phase II Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia. Cancer Discov. 2016, 6, 1106–1117. [Google Scholar] [CrossRef]
- Jin, S.; Cojocari, D.; Purkal, J.J.; Popovic, R.; Talaty, N.N.; Xiao, Y.; Solomon, L.R.; Boghaert, E.R.; Leverson, J.D.; Phillips, D.C. 5-Azacitidine Induces NOXA to Prime AML Cells for Venetoclax-Mediated Apoptosis. Clin. Cancer Res. 2020, 26, 3371–3383. [Google Scholar] [CrossRef]
- Bogenberger, J.M.; Delman, D.; Hansen, N.; Valdez, R.; Fauble, V.; Mesa, R.A.; Tibes, R. Ex vivo activity of BCL-2 family inhibitors ABT-199 and ABT-737 combined with 5-azacytidine in myeloid malignancies. Leuk. Lymphoma 2015, 56, 226–229. [Google Scholar] [CrossRef]
- DiNardo, C.D.; Pratz, K.W.; Jonas, B.A.; Wei, A.H.; Thirman, M.J.; Arellano, M.; Frattini, M.G.; Kantarjian, H.; Popovic, R.; Chyla, B.; et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukemia: A non-randomised, open-label, phase 1b study. Lancet Oncol. 2018, 19, 216–228. [Google Scholar] [CrossRef] [PubMed]
- Dinardo, C.D.; Jonas, B.A.; Pullarkat, V.; Thirman, M.J.; Garcia, J.S.; Wei, A.H.; Konopleva, M.; Döhner, H.; Letai, A.; Fenaux, P.; et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N. Engl. J. Med. 2020, 383, 617–629. [Google Scholar] [CrossRef] [PubMed]
- Wei, A.H.; Montesinos, P.; Ivanov, V.; DiNardo, C.D.; Novak, J.; Laribi, K.; Kim, I.; Stevens, D.A.; Fiedler, W.; Pagoni, M.; et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: A phase 3 randomized placebo-controlled trial. Blood 2020, 135, 2137–2145. [Google Scholar] [CrossRef]
- Cherry, E.M.; Abbott, D.; Amaya, M.; McMahon, C.; Schwartz, M.; Rosser, J.; Sato, A.; Schowinsky, J.; Inguva, A.; Minhajuddin, M.; et al. Venetoclax and azacitidine compared with induction chemotherapy for newly diagnosed patients with acute myeloid leukemia. Blood Adv. 2021, 5, 5565–5573. [Google Scholar] [CrossRef] [PubMed]
- Récher, C.; Röllig, C.; Bérard, E.; Bertoli, S.; Dumas, P.Y.; Tavitian, S.; Kramer, M.; Serve, H.; Bornhäuser, M.; Platzbecker, U.; et al. Long-term survival after intensive chemotherapy or hypomethylating agents in AML patients aged 70 years and older: A large patient data set study from European registries. Leukemia 2022, 36, 913–922. [Google Scholar] [CrossRef]
- Fiskus, W.; Boettcher, S.; Daver, N.; Mill, C.P.; Sasaki, K.; Birdwell, C.E.; Davis, J.A.; Takahashi, K.; Kadia, T.M.; DiNardo, C.D.; et al. Effective Menin inhibitor-based combinations against AML with MLL rearrangement or NPM1 mutation (NPM1c). Blood Cancer J. 2022, 12, 5. [Google Scholar] [CrossRef] [PubMed]
- Fiskus, W.; Daver, N.; Boettcher, S.; Mill, C.P.; Sasaki, K.; Birdwell, C.E.; Davis, J.A.; Das, K.; Takahashi, K.; Kadia, T.M.; et al. Activity of menin inhibitor ziftomenib (KO-539) as monotherapy or in combinations against AML cells with MLL1 rearrangement or mutant NPM1. Leukemia 2022, 36, 2729–2733. [Google Scholar] [CrossRef] [PubMed]
- Issa, G.C.; Zarka, J.; Sasaki, K.; Qiao, W.; Pak, D.; Ning, J.; Short, N.J.; Haddad, F.; Tang, Z.; Patel, K.P.; et al. Predictors of outcomes in adults with acute myeloid leukemia and KMT2A rearrangements. Blood Cancer J. 2021, 11, 162. [Google Scholar] [CrossRef]
- Jabbour, E.; Faderl, S.; Sasaki, K.; Kadia, T.; Daver, N.; Pemmaraju, N.; Patel, K.; Khoury, J.D.; Bueso-Ramos, C.; Bohannan, Z.; et al. Phase 2 study of low-dose clofarabine plus cytarabine for patients with higher-risk myelodysplastic syndrome who have relapsed or are refractory to hypomethylating agents. Cancer 2016, 123, 629–637. [Google Scholar] [CrossRef]
- Jabbour, E.; Short, N.J.; Montalban-Bravo, G.; Huang, X.; Bueso-Ramos, C.; Qiao, W.; Yang, H.; Zhao, C.; Kadia, T.; Borthakur, G.; et al. Randomized phase 2 study of low-dose decitabine vs low-dose azacitidine in lower-risk MDS and MDS/MPN. Blood 2017, 130, 1514–1522. [Google Scholar] [CrossRef] [PubMed]
- Sasaki, K.; Montalban-Bravo, G.; Kanagal-Shamanna, R.; Jabbour, E.; Ravandi, F.; Kadia, T.; Daver, N.; Pemmaraju, N.; Konopleva, M.; Borthakur, G.; et al. Natural history of newly diagnosed myelodysplastic syndrome with isolated inv(3)/t(3;3). Am. J. Hematol. 2020, 95, E326–E329. [Google Scholar] [CrossRef] [PubMed]
- Montalban-Bravo, G.; Kanagal-Shamanna, R.; Benton, C.B.; Class, C.A.; Chien, K.S.; Sasaki, K.; Naqvi, K.; Alvarado, Y.; Kadia, T.M.; Ravandi, F.; et al. Genomic context and TP53 allele frequency define clinical outcomes in TP53-mutated myelodysplastic syndromes. Blood Adv. 2020, 4, 482–495. [Google Scholar] [CrossRef] [PubMed]
- Montalban-Bravo, G.; Class, C.A.; Ganan-Gomez, I.; Kanagal-Shamanna, R.; Sasaki, K.; Richard-Carpentier, G.; Naqvi, K.; Wei, Y.; Yang, H.; Soltysiak, K.A.; et al. Transcriptomic analysis implicates necroptosis in disease progression and prognosis in myelodysplastic syndromes. Leukemia 2019, 34, 872–881. [Google Scholar] [CrossRef]
- Montalban-Bravo, G.; Kanagal-Shamanna, R.; Sasaki, K.; Patel, K.; Ganan-Gomez, I.; Jabbour, E.; Kadia, T.; Ravandi, F.; DiNardo, C.; Borthakur, G.; et al. NPM1 mutations define a specific subgroup of MDS and MDS/MPN patients with favorable outcomes with intensive chemotherapy. Blood Adv. 2019, 3, 922–933. [Google Scholar] [CrossRef]
- Naqvi, K.; Sasaki, K.; Montalban-Bravo, G.; Pierola, A.A.; Yilmaz, M.; Short, N.; Assi, R.; Jabbour, E.; Ravandi, F.; Kadia, T.; et al. Clonal hematopoiesis of indeterminate potential-associated mutations and risk of comorbidities in patients with myelodysplastic syndrome. Cancer 2019, 125, 2233–2241. [Google Scholar] [CrossRef]
- Short, N.J.; Jabbour, E.; Naqvi, K.; Patel, A.; Ning, J.; Sasaki, K.; Nogueras-Gonzalez, G.M.; Bose, P.; Kornblau, S.M.; Takahashi, K.; et al. A phase II study of omacetaxine mepesuccinate for patients with higher-risk myelodysplastic syndrome and chronic myelomonocytic leukemia after failure of hypomethylating agents. Am. J. Hematol. 2018, 94, 74–79. [Google Scholar] [CrossRef]
- Darbaniyan, F.; Zheng, H.; Kanagal-Shamanna, R.; Lockyer, P.; Montalban-Bravo, G.; Estecio, M.; Lu, Y.; Soltysiak, K.A.; Chien, K.S.; Yang, H.; et al. Transcriptomic Signatures of Hypomethylating Agent Failure in Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia. Exp. Hematol. 2022, 115, 44–53. [Google Scholar] [CrossRef]
- DiNardo, C.D.; Venugopal, S.; Lachowiez, C.A.; Takahashi, K.; Loghavi, S.; Montalban-Bravo, G.; Wang, X.; Carraway, H.E.; Sekeres, M.A.; Sukkur, A.; et al. Targeted therapy with the mutant IDH2 inhibitor enasidenib for high-risk IDH2-mutant myelodysplastic syndrome. Blood Adv. 2022. Online ahead of print. [Google Scholar] [CrossRef]
- Yang, H.; Garcia-Manero, G.; Sasaki, K.; Montalban-Bravo, G.; Tang, Z.; Wei, Y.; Kadia, T.; Chien, K.; Rush, D.; Nguyen, H.; et al. High-resolution structural variant profiling of myelodysplastic syndromes by optical genome mapping uncovers cryptic aberrations of prognostic and therapeutic significance. Leukemia 2022, 36, 2306–2316. [Google Scholar] [CrossRef]
- Sakhdari, A.; Class, C.; Montalban-Bravo, G.; Sasaki, K.; Bueso-Ramos, C.E.; Patel, K.P.; Routbort, M.J.; Loghavi, S.; Ok, C.Y.; Quesada, A.; et al. Immunohistochemical loss of enhancer of Zeste Homolog 2 (EZH2) protein expression correlates with EZH2 alterations and portends a worse outcome in myelodysplastic syndromes. Mod. Pathol. 2022, 35, 1212–1219. [Google Scholar] [CrossRef] [PubMed]
- Kanagal-Shamanna, R.; Montalban-Bravo, G.; Sasaki, K.; Darbaniyan, F.; Jabbour, E.; Bueso-Ramos, C.; Wei, Y.; Chien, K.; Kadia, T.; Ravandi, F.; et al. Only SF3B1 mutation involving K700E independently predicts overall survival in myelodysplastic syndromes. Cancer 2021, 127, 3552–3565. [Google Scholar] [CrossRef] [PubMed]
- Montalban-Bravo, G.; Kanagal-Shamanna, R.; Darbaniyan, F.; Siddiqui, M.T.; Sasaki, K.; Wei, Y.; Yang, H.; Chien, K.S.; Naqvi, K.; Jabbour, E.; et al. Clinical, genomic, and transcriptomic differences between myelodysplastic syndrome/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T) and myelodysplastic syndrome with ring sideroblasts (MDS-RS). Am. J. Hematol. 2021, 96, E246–E249. [Google Scholar] [CrossRef] [PubMed]
- Sasaki, K.; Jabbour, E.; Montalban-Bravo, G.; Darbaniyan, F.; Do, K.A.; Class, C.; Short, N.J.; Kanagal-Shamana, R.; Kadia, T.; Borthakur, G. Low-Dose Decitabine versus Low-Dose Azacitidine in Lower-Risk MDS. NEJM Evid. 2022, 1, EVIDoa2200034. [Google Scholar] [CrossRef]
- Lancet, J.; Uy, G.; Newell, L.; Lin, T.; Richie, E.; Stuart, R.; Strickland, S.A.; Hogge, D.; Solomon, S.R.; Bixby, D.L.; et al. CPX-351 versus 7+3 cytarabine and daunorubicin chemotherapy in older adults with newly diagnosed high-risk or secondary acute myeloid leukaemia: 5-year results of a randomised, open-label, multicentre, phase 3 trial. Lancet Haematol. 2021, 8, e481–e491. [Google Scholar] [CrossRef]
- Matthews, A.H.; Perl, A.E.; Luger, S.M.; Loren, A.W.; Gill, S.I.; Porter, D.L.; Babushok, D.V.; Maillard, I.P.; Carroll, M.P.; Frey, N.V.; et al. Real-world effectiveness of CPX-351 vs venetoclax and azacitidine in acute myeloid leukemia. Blood Adv. 2022, 6, 3997–4005. [Google Scholar] [CrossRef] [PubMed]
- Min, G.-J.; Cho, B.-S.; Park, S.-S.; Park, S.; Jeon, Y.-W.; Shin, S.-H.; Yahng, S.-A.; Yoon, J.-H.; Lee, S.-E.; Eom, K.-S.; et al. Geriatric assessment predicts nonfatal toxicities and survival for intensively treated older adults with AML. Blood 2022, 139, 1646–1658. [Google Scholar] [CrossRef]
Category | Prognostic Score | |
---|---|---|
Demographic data | ||
Age (year) | <40 | 0 |
40–64 | +2 | |
64–75 | +3 | |
75+ | +7 | |
ECOG PS | 0–1 | 0 |
2 | +1 | |
3–4 | +6 | |
Laboratory data | ||
Total bilirubin (mg/dL) | <1.3 | 0 |
≥1.3 | +1 | |
Creatinine (mg/dL) | <1.3 | 0 |
≥1.3 | +2 | |
Uric acid (mg/dL) | <10 | 0 |
≥10 | +2 | |
Chromosomal abnormalities | ||
Diploid (including -Y)/core binding factor | 0 | |
Others/complex | +1 | |
Infection at diagnosis | ||
Pneumonia | +2 | |
Four-week mortality by the proposed risk classification in 2010–2020 | ||
Low: Total scores ≤ 4 | 2% | |
High: Total socres 5–8 | 13% | |
Very high: Total score ≥ 9 | 30% |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Oshikawa, G.; Sasaki, K. Optimizing Treatment Options for Newly Diagnosed Acute Myeloid Leukemia in Older Patients with Comorbidities. Cancers 2023, 15, 2399. https://doi.org/10.3390/cancers15082399
Oshikawa G, Sasaki K. Optimizing Treatment Options for Newly Diagnosed Acute Myeloid Leukemia in Older Patients with Comorbidities. Cancers. 2023; 15(8):2399. https://doi.org/10.3390/cancers15082399
Chicago/Turabian StyleOshikawa, Gaku, and Koji Sasaki. 2023. "Optimizing Treatment Options for Newly Diagnosed Acute Myeloid Leukemia in Older Patients with Comorbidities" Cancers 15, no. 8: 2399. https://doi.org/10.3390/cancers15082399
APA StyleOshikawa, G., & Sasaki, K. (2023). Optimizing Treatment Options for Newly Diagnosed Acute Myeloid Leukemia in Older Patients with Comorbidities. Cancers, 15(8), 2399. https://doi.org/10.3390/cancers15082399