Skip to main content
Top
Published in: Annals of Hematology 4/2019

01-04-2019 | Acute Myeloid Leukemia | Original Article

Treatment patterns and comparative analysis of non-intensive regimens in elderly acute myeloid leukemia patients—a real-world experience from India

Authors: Govind B. Kanakasetty, Chethan R, Lakshmaiah K C, Lokanatha Dasappa, Linu Abraham Jacob, Suresh Babu M C, Lokesh K N, Rudresha Antapura Haleshappa, Rajeev L K, Smitha Carol Saldanha, Koppaka Deepak, Patidar Rajesh, Vikas Asati

Published in: Annals of Hematology | Issue 4/2019

Login to get access

Abstract

Elderly patients with acute myeloid leukemia have a poor prognosis. Data from developing countries is sparse in the literature. In this retrospective study, 402 patients aged ≥ 60 years, diagnosed between Jan 2013 and Dec 2017, were analyzed for treatment patterns and survival. Median age of the whole cohort was 68 years (range 61–84). A total of 213 patients (53.3%) refused care; 188 patients (46.7%) received either BSC, LDAC, or HMA. Survival (in months) was 3.9, 6.4, and 1.2 with LDAC, HMA, and BSC, respectively. One-year survival was 17.2% and 6% with HMA and LDAC, respectively (P = 0.02). Overall response rate (ORR) did not differ between HMA and LDAC group (p = 0.12). HMA cohort had higher complete responses (20.6% vs 7.4%, p = 0.02), stable disease (32.7% vs 13.5%, p = 0.02), and transfusion independence (TI) (46.5% vs 22.2%, p = 0.01). Survival did not differ between the groups if the patients achieved ORR (12.3 vs 9.8 p = 0.2) or TI (11.6 vs 6.4 p = 0.2). Stable disease with HMA led to longer survival (8.1 vs 5.3 p = 0.01). HMAs were more effective than LDAC irrespective of cytogenetic risk category and blasts, of note HMAs improved survival of poor risk patients (5.6 vs 2.9 p = 0.004). HMA treatment (HR = 0.48; 95% 0.29–0.79, p = 0.004) and transfusion independence (HR = 0.2; 95% 0.1–0.3, p = 0.0001) predicted survival in multivariate analysis. Neutropenia and febrile neutropenia were frequent in HMA. Thrombocytopenia was the common adverse event with LDAC. Novel and cost-effective drugs are essential to improve the prognosis of these patients.
Literature
1.
2.
go back to reference Klepin HD, Balducci L (2009) Acute myelogenous leukemia in older adults. Oncologist 14(3):222–232CrossRefPubMed Klepin HD, Balducci L (2009) Acute myelogenous leukemia in older adults. Oncologist 14(3):222–232CrossRefPubMed
3.
go back to reference Alibhai SMH, Leach M, Minden MD, Brandwein J (2009) Outcomes and quality of care in acute myeloid leukemia over 40 years. Cancer 115(13):2903–2911CrossRefPubMed Alibhai SMH, Leach M, Minden MD, Brandwein J (2009) Outcomes and quality of care in acute myeloid leukemia over 40 years. Cancer 115(13):2903–2911CrossRefPubMed
4.
go back to reference Leith CP, Kopecky KJ, Chen IM, McConnell T, Slovak ML, Head DR, et al AML in the Elderly: a Biologically Distinct Disease in which MDR1 Expression and Unfavorable Cytogenetics Contribute to Poor Clinical Response. Studies of the Southwest Oncology Group. In: Acute Leukemias VII. Berlin, Heidelberg: Springer Berlin Heidelberg; 1998. pp. 413–21. (Haematology and Blood Transfusion / Hämatologie und Bluttransfusion; vol. 39) Leith CP, Kopecky KJ, Chen IM, McConnell T, Slovak ML, Head DR, et al AML in the Elderly: a Biologically Distinct Disease in which MDR1 Expression and Unfavorable Cytogenetics Contribute to Poor Clinical Response. Studies of the Southwest Oncology Group. In: Acute Leukemias VII. Berlin, Heidelberg: Springer Berlin Heidelberg; 1998. pp. 413–21. (Haematology and Blood Transfusion / Hämatologie und Bluttransfusion; vol. 39)
5.
go back to reference Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK et al (2007) 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 109(6):1114–1124CrossRefPubMed Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK et al (2007) 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 109(6):1114–1124CrossRefPubMed
6.
go back to reference Fathi AT, Abdel-Wahab O (2012) Mutations in epigenetic modifiers in myeloid malignancies and the prospect of novel epigenetic-targeted therapy. Adv Hematol 2012(12):469592–469512 Fathi AT, Abdel-Wahab O (2012) Mutations in epigenetic modifiers in myeloid malignancies and the prospect of novel epigenetic-targeted therapy. Adv Hematol 2012(12):469592–469512
7.
go back to reference Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Finelli C, Giagounidis A et al (2009) 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 10(3):223–232CrossRefPubMedPubMedCentral Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Finelli C, Giagounidis A et al (2009) 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 10(3):223–232CrossRefPubMedPubMedCentral
8.
go back to reference Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J et al (2012) 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 30(21):2670–2677CrossRefPubMedPubMedCentral Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J et al (2012) 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 30(21):2670–2677CrossRefPubMedPubMedCentral
9.
go back to reference Smith BD, Beach CL, Mahmoud D, Weber L, Henk HJ (2014) Survival and hospitalization among patients with acute myeloid leukemia treated with azacitidine or decitabine in a large managed care population: a real-world, retrospective, claims-based, comparative analysis. Exp Hematol Oncol 3(1):10CrossRefPubMedPubMedCentral Smith BD, Beach CL, Mahmoud D, Weber L, Henk HJ (2014) Survival and hospitalization among patients with acute myeloid leukemia treated with azacitidine or decitabine in a large managed care population: a real-world, retrospective, claims-based, comparative analysis. Exp Hematol Oncol 3(1):10CrossRefPubMedPubMedCentral
10.
go back to reference Ozbalak M, Cetiner M, Bekoz H, Atesoglu EB, Ar C, Salihoglu A et al (2012) Azacitidine has limited activity in “real life” patients with MDS and AML: a single centre experience. Hematol Oncol 30(2):76–81CrossRefPubMed Ozbalak M, Cetiner M, Bekoz H, Atesoglu EB, Ar C, Salihoglu A et al (2012) Azacitidine has limited activity in “real life” patients with MDS and AML: a single centre experience. Hematol Oncol 30(2):76–81CrossRefPubMed
11.
go back to reference Radujkovic A, Dietrich S, Bochtler T, Krämer A, Schöning T, Ho AD et al (2014) Azacitidine and low-dose cytarabine in palliative patients with acute myeloid leukemia and high bone marrow blast counts – a retrospective single-center experience. Eur J Haematol 93(2):112–117CrossRefPubMed Radujkovic A, Dietrich S, Bochtler T, Krämer A, Schöning T, Ho AD et al (2014) Azacitidine and low-dose cytarabine in palliative patients with acute myeloid leukemia and high bone marrow blast counts – a retrospective single-center experience. Eur J Haematol 93(2):112–117CrossRefPubMed
12.
go back to reference Jacob LA, Aparna S, Lakshmaiah KC, Lokanatha D, Babu G, Babu S et al (2015) Decitabine compared with low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia: a pilot study of safety, efficacy, and cost-effectiveness. Adv Hematol 2015(12):1–6CrossRef Jacob LA, Aparna S, Lakshmaiah KC, Lokanatha D, Babu G, Babu S et al (2015) Decitabine compared with low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia: a pilot study of safety, efficacy, and cost-effectiveness. Adv Hematol 2015(12):1–6CrossRef
13.
go back to reference Philip C, George B, Ganapule A, Korula A, Jain P, Alex AA et al (2015) Acute myeloid leukaemia: challenges and real world data from India. Br J Haematol 170(1):110–117CrossRefPubMedPubMedCentral Philip C, George B, Ganapule A, Korula A, Jain P, Alex AA et al (2015) Acute myeloid leukaemia: challenges and real world data from India. Br J Haematol 170(1):110–117CrossRefPubMedPubMedCentral
14.
go back to reference Mukhopadhyay S, Chitalkar P, Gupta P, Roy U, Mukhopadhyay A (2016) Oral chemotherapeutic agents in elderly acute myeloid leukemia (AML) patients, a study from a developing country. Journal of Clinical Oncology. American Society of Clinical Oncology Mukhopadhyay S, Chitalkar P, Gupta P, Roy U, Mukhopadhyay A (2016) Oral chemotherapeutic agents in elderly acute myeloid leukemia (AML) patients, a study from a developing country. Journal of Clinical Oncology. American Society of Clinical Oncology
15.
go back to reference Kapoor A, Beniwal SK, Kalwar A, Singhal MK, Nirban RK, Kumar HS (2016) Metronomic therapy with oral 6-mercaptopurine in elderly acute myeloid leukemia: a prospective pilot study. South Asian J Cancer 5(2):70–72CrossRefPubMedPubMedCentral Kapoor A, Beniwal SK, Kalwar A, Singhal MK, Nirban RK, Kumar HS (2016) Metronomic therapy with oral 6-mercaptopurine in elderly acute myeloid leukemia: a prospective pilot study. South Asian J Cancer 5(2):70–72CrossRefPubMedPubMedCentral
16.
go back to reference Tandon N, Banavali S, Menon H, Gujral S, Kadam PA, Bakshi A (2013) Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review. Indian J Cancer 50(2):154–158CrossRefPubMed Tandon N, Banavali S, Menon H, Gujral S, Kadam PA, Bakshi A (2013) Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review. Indian J Cancer 50(2):154–158CrossRefPubMed
17.
go back to reference Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, et al (2010) Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities amongst 5,876 younger adult patients treated in the UK Medical Research Council trials. Blood. American Society of Hematology 116(3):blood–2009–11–254441–365 Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, et al (2010) Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities amongst 5,876 younger adult patients treated in the UK Medical Research Council trials. Blood. American Society of Hematology 116(3):blood–2009–11–254441–365
18.
go back to reference Gavillet M, Noetzli J, Blum S, Duchosal MA, Spertini O, Lambert J-F (2012) Transfusion independence and survival in patients with acute myeloid leukemia treated with 5azacytidine. Haematologica 97(12):1929–1931CrossRefPubMedPubMedCentral Gavillet M, Noetzli J, Blum S, Duchosal MA, Spertini O, Lambert J-F (2012) Transfusion independence and survival in patients with acute myeloid leukemia treated with 5azacytidine. Haematologica 97(12):1929–1931CrossRefPubMedPubMedCentral
19.
go back to reference Al-Ali HK, Jaekel N, Junghanss C, Maschmeyer G, Krahl R, Cross M et al (2011) Azacitidine in patients with acute myeloid leukemia medically unfit for or resistant to chemotherapy: a multicenter phase I/II study. Leuk Lymphoma 53(1):110–117CrossRefPubMed Al-Ali HK, Jaekel N, Junghanss C, Maschmeyer G, Krahl R, Cross M et al (2011) Azacitidine in patients with acute myeloid leukemia medically unfit for or resistant to chemotherapy: a multicenter phase I/II study. Leuk Lymphoma 53(1):110–117CrossRefPubMed
20.
go back to reference Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C (2015) Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol 94(7):1127–1138CrossRefPubMedPubMedCentral Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C (2015) Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol 94(7):1127–1138CrossRefPubMedPubMedCentral
21.
go back to reference Ma E, Bonthapally V, Chawla A, Lefebvre P, Swords R, Lafeuille M-H et al (2016) An evaluation of treatment patterns and outcomes in elderly patients newly diagnosed with acute myeloid leukemia: a retrospective analysis of electronic medical records from US community oncology practices. Clin Lymphoma Myeloma Leuk 16(11):625–636.e3CrossRefPubMed Ma E, Bonthapally V, Chawla A, Lefebvre P, Swords R, Lafeuille M-H et al (2016) An evaluation of treatment patterns and outcomes in elderly patients newly diagnosed with acute myeloid leukemia: a retrospective analysis of electronic medical records from US community oncology practices. Clin Lymphoma Myeloma Leuk 16(11):625–636.e3CrossRefPubMed
22.
23.
go back to reference Juliusson G, Lazarevic V, Hörstedt A-S, Hagberg O, Höglund M, Swedish Acute Leukemia Registry Group (2012) Acute myeloid leukemia in the real world: why populationbased registries are needed. Blood 119(17):3890–3899CrossRefPubMedPubMedCentral Juliusson G, Lazarevic V, Hörstedt A-S, Hagberg O, Höglund M, Swedish Acute Leukemia Registry Group (2012) Acute myeloid leukemia in the real world: why populationbased registries are needed. Blood 119(17):3890–3899CrossRefPubMedPubMedCentral
24.
go back to reference Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447CrossRefPubMedPubMedCentral Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447CrossRefPubMedPubMedCentral
25.
go back to reference Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH et al (2015) International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood 126(3):291–299CrossRefPubMedPubMedCentral Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH et al (2015) International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood 126(3):291–299CrossRefPubMedPubMedCentral
26.
go back to reference Serrano J, de la Fuente A, Bergua J, Falantes J, Eusebio M-C, Antonio LJ et al (2011) 5Azacytidine versus intensive chemotherapy or BSC in elderly (>60 years) acute myeloid leukemia patients. A retrospective analysis. Blood 118(21):2612–2612 Serrano J, de la Fuente A, Bergua J, Falantes J, Eusebio M-C, Antonio LJ et al (2011) 5Azacytidine versus intensive chemotherapy or BSC in elderly (>60 years) acute myeloid leukemia patients. A retrospective analysis. Blood 118(21):2612–2612
27.
go back to reference Thépot S, Itzykson R, Seegers V, Récher C, Raffoux E, Quesnel B et al (2014) Azacitidine in untreated acute myeloid leukemia: a report on 149 patients. Am J Hematol 89(4):410–416CrossRefPubMed Thépot S, Itzykson R, Seegers V, Récher C, Raffoux E, Quesnel B et al (2014) Azacitidine in untreated acute myeloid leukemia: a report on 149 patients. Am J Hematol 89(4):410–416CrossRefPubMed
28.
go back to reference Ramos F, Thépot S, Pleyer L, Maurillo L, Itzykson R, Bargay J et al (2015) Azacitidine frontline therapy for unfit acute myeloid leukemia patients: clinical use and outcome prediction. Leuk Res 39(3):296–306CrossRefPubMed Ramos F, Thépot S, Pleyer L, Maurillo L, Itzykson R, Bargay J et al (2015) Azacitidine frontline therapy for unfit acute myeloid leukemia patients: clinical use and outcome prediction. Leuk Res 39(3):296–306CrossRefPubMed
29.
go back to reference Schuh AC, Döhner H, Seymour JF, Turlure P, Junghanss C, MacWhannell A et al (2017) Stable disease with hematologic improvement is clinically meaningful for older patients with Acute Myeloid Leukemia (AML) treated with azacitidine. Leuk Res 55:S68–S69CrossRef Schuh AC, Döhner H, Seymour JF, Turlure P, Junghanss C, MacWhannell A et al (2017) Stable disease with hematologic improvement is clinically meaningful for older patients with Acute Myeloid Leukemia (AML) treated with azacitidine. Leuk Res 55:S68–S69CrossRef
30.
go back to reference Seymour JF, Fenaux P, Silverman LR, Mufti GJ, Hellström-Lindberg E, Santini V et al (2010) Effects of azacitidine compared with conventional care regimens in elderly (≥ 75 years) patients with higher-risk myelodysplastic syndromes. Crit Rev Oncol Hematol 76(3):218–227CrossRefPubMedPubMedCentral Seymour JF, Fenaux P, Silverman LR, Mufti GJ, Hellström-Lindberg E, Santini V et al (2010) Effects of azacitidine compared with conventional care regimens in elderly (≥ 75 years) patients with higher-risk myelodysplastic syndromes. Crit Rev Oncol Hematol 76(3):218–227CrossRefPubMedPubMedCentral
Metadata
Title
Treatment patterns and comparative analysis of non-intensive regimens in elderly acute myeloid leukemia patients—a real-world experience from India
Authors
Govind B. Kanakasetty
Chethan R
Lakshmaiah K C
Lokanatha Dasappa
Linu Abraham Jacob
Suresh Babu M C
Lokesh K N
Rudresha Antapura Haleshappa
Rajeev L K
Smitha Carol Saldanha
Koppaka Deepak
Patidar Rajesh
Vikas Asati
Publication date
01-04-2019
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 4/2019
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-019-03600-6

Other articles of this Issue 4/2019

Annals of Hematology 4/2019 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.