Real-world survival analysis of elderly patients with acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) predominantly affects the elderly, who often have a poor prognosis due to age-related comorbidities, adverse genetic features, and limited tolerance to standard therapies. This study aimed to evaluate real-world survival outcomes and prognostic factors in elderly patients with AML to improve clinical management. A retrospective analysis was conducted on 179 elderly AML patients across multiple centers over 6 years. Clinical features, bone marrow characteristics, vital status, and prognostic factors were analyzed. Kaplan-Meier was used to estimate overall survival, while univariate and multivariate regression analyzes identified prognostic factors. The median overall survival (mOS) of the cohort was 5.3 months. Patients in the chemotherapy group (n = 126) showed better mOS than those in the support therapy group (n = 53) (7.567 vs. 3 months; p<0.0001). Among chemotherapy patients, those treated with hypomethylating agents (HMAs) (n = 54) had better mOS compared to cytotoxic chemotherapy (n = 72) (10.17 vs. 4.1 months; p<0.0001). Within the HMA group, no significant difference in mOS was found between HMA monotherapy (n = 9) and HMA plus venetoclax (VEN) (n = 45) (9.117 vs. 10.17 months; p=0.3407). In patients eligible for intensive chemotherapy, the HMA group had a superior mOS than the cytotoxic chemotherapy group (9.4 vs. 3.933 months; p<0.0001). The top five mutations identified were NPM1 (29.59%), FT3-internal tandem duplication (ITD) (26.53%), DNMT3A (25.51%), IDH2 (20.41%), and CEBPA (14.29%), with DNMT3A-FLT3-ITD, NPM1-FLT3-ITD, and NPM1-DNMT3A showing significantly higher co-mutation frequencies than the other combinations. In addition, infection was the most frequent complication (60%). Elderly AML patients have poor mOS and a high burden of adverse genetic features. Chemotherapy, especially HMAs alone or combined with VEN, is associated with improved survival and better clinical outcomes compared to supportive care or intensive regimens. These findings provide real-world evidence to inform treatment strategies.

Keywords

Elderly / Acute myeloid leukemia / Hypomethylating agents / Cytotoxic chemotherapy / Survival analysis / Prognostic factors

Funding

This study is supported by the Research and Innovation Team Project for Scientific Breakthroughs at Shanxi Bethune Hospital, No. 2024ZHANCHI12.

Conflict of interest

Jia Wei is an Associate Editor of this journal, but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.

References

[1] Stubbins RJ, Francis A, Kuchenbauer F, Sanford D. Management of acute myeloid leukemia: A review for general practitioners in oncology. Curr Oncol. 2022; 29(9):6245-6259. doi: 10.3390/curroncol29090491

[2] DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020; 383(7):617-629. doi: 10.1056/NEJMoa2012971

[3] Kang Y, Zhang S, Cao W, Wan D, Sun L. Knockdown of LncRNA CRNDE suppresses proliferation and P-glycoprotein-mediated multidrug resistance in acute myelocytic leukemia through the Wnt/β-catenin pathway. Biosci Rep. 2020; 40(6):BSR20193450. doi: 10.1042/BSR20193450

[4] Bernard E, Nannya Y, Hasserjian RP, et al. Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes. Nat Med. 2020; 26(10):1549-1556. doi: 10.1038/s41591-020-1008-z

[5] Erba HP, Montesinos P, Kim HJ, et al. Quizartinib plus chemotherapy in newly diagnosed patients with FLT3-internal-tandem-duplication-positive acute myeloid leukaemia (QuANTUM-First): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023; 401(10388):1571-1583. doi: 10.1016/S0140-6736(23)00464-6

[6] Senapati J, Kadia TM, Ravandi F. Maintenance therapy in acute myeloid leukemia: Advances and controversies. Haematologica. 2023; 108(9):2289-2304. doi: 10.3324/haematol.2022.281810

[7] Thol F, Ganser A. Treatment of relapsed acute myeloid leukemia. Curr Treat Options Oncol. 2020; 21(8):66. doi: 10.1007/s11864-020-00765-5

[8] Bhansali RS, Pratz KW, Lai C. Recent advances in targeted therapies in acute myeloid leukemia. J Hematol Oncol. 2023; 16(1):29. doi: 10.1186/s13045-023-01424-6

[9] Pratz KW, Jonas BA, Pullarkat V, et al. Long-term follow-up of VIALE-A: Venetoclax and azacitidine in chemotherapy-ineligible untreated acute myeloid leukemia. Am J Hematol. 2024; 99(4):615-624. doi: 10.1002/ajh.27246

[10] Cherry EM, Abbott D, Amaya M, et al. Venetoclax and azacitidine compared with induction chemotherapy for newly diagnosed patients with acute myeloid leukemia. Blood Adv. 2021; 5(24):5565-5573. doi: 10.1182/bloodadvances.2021005538

[11] Cortes JE, Heidel FH, Hellmann A, et al. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019; 33(2):379-389. doi: 10.1038/s41375-018-0312-9

[12] Wei AH, Strickland SAJ, Hou JZ, et al. Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: Results from a phase Ib/II study. J Clin Oncol. 2019; 37(15):1277-1284. doi: 10.1200/JCO.18.01600

[13] Pollyea DA, Altman JK, Assi R, et al. Acute myeloid leukemia, version 3.2023, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2023; 21(5):503-513. doi: 10.6004/jnccn.2023.0025

[14] Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 Recommendations from an international expert panel on behalf of the ELN. Blood. 2022; 140(12):1345-1377. doi: 10.1182/blood.2022016867

[15] Venditti A, Cairoli R, Caira M, et al. Assessing eligibility for treatment in acute myeloid leukemia in 2023. Expert Rev Hematol. 2023; 16(3):181-190. doi: 10.1080/17474086.2023.2185603

[16] Narlı Özdemir Z, Kılıçaslan NA, Yılmaz M, Eşkazan AE. Guidelines for the treatment of chronic myeloid leukemia from the NCCN and ELN: Differences and similarities. Int J Hematol. 2023; 117(1):3-15. doi: 10.1007/s12185-022-03446-1

[17] Juliusson G, Antunovic P, Derolf A, et al. Age and acute myeloid leukemia: Real world data on decision to treat and outcomes from the swedish acute leukemia registry. Blood. 2009; 113(18):4179-4187. doi: 10.1182/blood-2008-07-172007

[18] Wei AH, Döhner H, Pocock C, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020; 383(26):2526-2537. doi: 10.1056/NEJMoa2004444

[19] Alsouqi A, Geramita E, Im A. Treatment of acute myeloid leukemia in older adults. Cancers(Basel). 2023; 15(22):5409. doi: 10.3390/cancers15225409

[20] DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019; 133(1):7-17. doi: 10.1182/blood-2018-08-868752

[21] Greenwood MJ, Seftel MD, Richardson C, et al. Leukocyte count as a predictor of death during remission induction in acute myeloid leukemia. Leuk Lymphoma. 2006; 47(7):1245-1252. doi: 10.1080/10428190600572673

[22] Bocchia M, Candoni A, Borlenghi E, et al. Real-world experience with decitabine as a first-line treatment in 306 elderly acute myeloid leukaemia patients unfit for intensive chemotherapy. Hematol Oncol. 2019; 37(4):447-455. doi: 10.1002/hon.2663

[23] Pepe S, Scalzulli E, Colafigli G, et al. Predictive factors for response and survival in elderly acute myeloid leukemia patients treated with hypomethylating agents: A real-life experience. Ann Hematol. 2020; 99(10):2405-2416. doi: 10.1007/s00277-020-04217-w

[24] Wang B, Guan W, Lv N, et al. Genetic features and efficacy of decitabine-based chemotherapy in elderly patients with acute myeloid leukemia. Hematology. 2021; 26(1):371-379. doi: 10.1080/16078454.2021.1921434

[25] Bewersdorf JP, Shimony S, Shallis RM, et al. Intensive induction chemotherapy vs hypomethylating agents in combination with venetoclax in NPM1-mutant AML. Blood Adv. 2024; 8(18):4845-4855. doi: 10.1182/bloodadvances.2024012858

[26] Shabashvili DE, Feng Y, Kaur P, Venugopal K, Guryanova OA. Combination strategies to promote sensitivity to cytarabine-induced replication stress in acute myeloid leukemia with and without DNMT3A mutations. Exp Hematol. 2022; 110:20-27. doi: 10.1016/j.exphem.2022.03.008

[27] Gangat N, Karrar O, Iftikhar M, et al. Venetoclax and hypomethylating agent combination therapy in newly diagnosed acute myeloid leukemia: Genotype signatures for response and survival among 301 consecutive patients. Am J Hematol. 2024; 99(2):193-202. doi: 10.1002/ajh.27138

[28] Lu J, Chen M, Hua H, et al. Additional mutations in IDH1/2- mutated patients with acute myeloid leukemia. Int J Lab Hematol. 2021; 43(6):1483-1490. doi: 10.1111/ijlh.13648

[29] Linch DC, Hills RK, Burnett AK, Khwaja A, Gale RE. Impact of FLT3 (ITD) mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia. Blood. 2014; 124(2):273-276. doi: 10.1182/blood-2014-02-554667

[30] Othman J, Potter N, Ivey A, et al. Molecular, clinical, and therapeutic determinants of outcome in NPM1-mutated AML. Blood. 2024; 144(7):714-728. doi: 10.1182/blood.2024024310

[31] Wang H, Chu TT, Han SY, et al. FLT3-ITD and CEBPA mutations predict prognosis in acute myelogenous leukemia irrespective of hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2019; 25(5):941-948. doi: 10.1016/j.bbmt.2018.11.031