Comparison of low dose cytosine arabinoside, azacitidine and azacitidine venetoclax combination treatment as remission induction in elderly acute myeloid leukemia patients
Abstract
Aims: Low-intensity therapies are widely preferred in the treatment of advanced age, fragile acute myeloid leukemia (AML) patients. In this study, we aimed to compare hematological recovery rates after first cycle chemotherapy and overall survival for advanced aged AML patients treated with azacitidine (AZA) or low dose cytosine arabinoside (LDCA) or venetoclax (Ven) with AZA combination.
Methods: Ninety-one patients were retrospectively analyzed.
Results: Forty-one patients treated with LDCA, 30 patients treated with AZA and 20 patients treated with AZA+Ven were included in the study. Patients who received these three treatments and who achieved response and did not receive any other treatment during the follow-up period were included in the study. Median age at diagnosis was 70. The percentage of patients who achieved neutrophil recovery after the first cycle was 27%, 73% and 50% of the patients treated with LDCA, AZA and AZA+Ven respectively. The rate of patients who achieved platelet recovery was 60%, 80%, 70% respectively. Erythrocyte transfusion independency was 54% for LDCA patients, 73% for AZA patients and 60% for combination therapy. Overall survival was longer in patients receiving AZA+Ven than other treatment groups while grade 3-4 infections were more common in the first cycle of the treatment.
Conclusion: According to our study, patients treated with AZA had better platelet and neutrophil recovery rates with also longer overall survival than patients treated with LDCA, but total overall survival was superior in AZA+Ven combination. Hypomethylating agents with venetoclax is a preferable treatment option in elderly AML patients.
Keywords
Acute myeloid leukemia azacitidine low dose cytosine arabinoside venetoclax elderly patients
Ethical Statement
Çalışma için Yıldırım Beyazıt Üniversitesi Sağlık Bilimleri etik kurulundan 2020-483 araştırma kodu, 14/02/2021 tarih ve 67 sayısı ile onay alınmıştır.
Supporting Institution
Yoktur.
Thanks
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References
- Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM. Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev. 2019;36:70-87.
- Swolin B, Rödjer S, Westin J. Therapy-related patterns of cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome post polycythemia vera: single center experience and review of literature. Ann Hematol. 2008;87(6):467-474.
- Surveillance, Epidemiology, and End Results (SEER) Program Cancer Stat Facts: Leukemia-Acute Myeloid Leukemia (AML). Available at: https://seer.cancer.gov/statfacts/html/amyl.html
- Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447.
- Oran B, Weisdorf DJ. Survival for older patients with acute myeloid leukemia: a population-based study. Haematologica. 2012;97(12):1916-1924.
- Löwenberg B, Zittoun R, Kerkhofs H, et al. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol. 1989;7(9):1268-1274.
- Tilly H, Castaigne S, Bordessoule D, et al. Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol. 1990;8(2): 272-279.
- Fenaux P, Mufti GJ, Hellström-Lindberg E, 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(4):562-569.
- 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):291-299.
- 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.
- Guerra VA, DiNardo C, Konopleva M. Venetoclax-based therapies for acute myeloid leukemia. Best Pract Res Clin Haematol. 2019;32(2):145-153.
- 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.
- Pollyea DA, Altman JK, Assi R, et al. Acute myeloid leukemia, version 3.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023;21(5):503-513.
- Common Terminology Criteria for Adverse Events. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf (Accessed on March 09, 2018).
- García-Delgado R, de Miguel D, Bailén A, et al. Effectiveness and safety of different azacitidine dosage regimens in patients with myelodysplastic syndromes or acute myeloid leukemia. Leuk Res. 2014;38(7):744-750.
- Heiblig M, Elhamri M, Tigaud I, et al. Treatment with low-dose cytarabine in elderly patients (age 70 years or older) with acute myeloid leukemia: a single institution experience. Mediterr J Hematol Infect Dis. 2016;8(1):1-7.
- Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94(7):1127-1138.
- Babakhanlou R, Ravandi-Kashani F. Non-intensive acute myeloid leukemia therapies for older patients. Expert Rev Hematol. 2023;16(3):171-180.
- Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020; 135(24):2137-2145.
- Kenswil KJG, Pisterzi P, Feyen J, et al. Immune composition and its association with hematologic recovery after chemotherapeutic injury in acute myeloid leukemia. Exp Hematol. 2022;105:32-38.
Yaşlı akut miyeloid lösemili hastalarda remisyon indüksiyonu olarak düşük doz sitozin arabinosid, azasitidin ve azasitidin venetoklaks kombinasyon tedavisinin karşılaştırılması
Abstract
Amaç: İleri yaş, kırılgan akut miyeloid lösemi (AML) hastalarının tedavisinde düşük yoğunluklu tedaviler yaygın olarak tercih edilmektedir. Bu çalışmada, düşük doz sitozin arabinosid (DDSA) veya azasitidin (AZA) veya AZA+venetoklaks (Ven) ile tedavi edilen ileri yaşlı AML hastalarının birinci siklus kemoterapi sonrası hematolojik iyileşme oranlarını ve genel sağkalımı karşılaştırmayı amaçladık.
Yöntem: Doksan bir hasta geriye yönelik olarak incelendi.
Bulgular: Çalışmaya DDSA ile tedavi edilen kırk bir hasta, AZA ile tedavi edilen 30 hasta ve AZA + Ven ile tedavi edilen 20 hasta dahil edildi. Tanıda ortanca yaş 70 idi. İlk kürden sonra nötrofil iyileşmesi gözlenen hastaların yüzdesi sırasıyla DDSA, AZA ve AZA +Ven tedavi gruplarında %27, %73 ve%50 idi. Trombosit iyileşmesi gözlenen hastaların oranı sırasıyla %60,%80,%70 idi. 1. kürün sonunda eritrosit transfüzyon bağımsızlığı DDSA hastaları için% 54, AZA hastaları için% 73 ve kombinasyon tedavisi için% 60 idi. AZA + Ven alan hastalarda genel sağkalım diğer tedavi gruplarına göre daha uzundu, ancak tedavinin ilk küründe grade 3-4 enfeksiyon bu hasta grubunda daha sık olarak bulundu.
SONUÇ: Çalışmamıza göre, AZA ile tedavi edilen hastalar, DDSA ile tedavi edilen hastalardan daha uzun genel sağkalım ile daha iyi trombosit ve nötrofil iyileşme oranlarına sahipti, ancak AZA + Ven kombinasyonunda toplam genel sağkalım üstündü. Yaşlı AML hastalarında venetoklaks ile hipometile edici ajan kombinasyonu uzun sağkalım nedeniyle tercih edilebilecek bir tedavi seçeneğidir.
References
- Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM. Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev. 2019;36:70-87.
- Swolin B, Rödjer S, Westin J. Therapy-related patterns of cytogenetic abnormalities in acute myeloid leukemia and myelodysplastic syndrome post polycythemia vera: single center experience and review of literature. Ann Hematol. 2008;87(6):467-474.
- Surveillance, Epidemiology, and End Results (SEER) Program Cancer Stat Facts: Leukemia-Acute Myeloid Leukemia (AML). Available at: https://seer.cancer.gov/statfacts/html/amyl.html
- Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424-447.
- Oran B, Weisdorf DJ. Survival for older patients with acute myeloid leukemia: a population-based study. Haematologica. 2012;97(12):1916-1924.
- Löwenberg B, Zittoun R, Kerkhofs H, et al. On the value of intensive remission-induction chemotherapy in elderly patients of 65+ years with acute myeloid leukemia: a randomized phase III study of the European Organization for Research and Treatment of Cancer Leukemia Group. J Clin Oncol. 1989;7(9):1268-1274.
- Tilly H, Castaigne S, Bordessoule D, et al. Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol. 1990;8(2): 272-279.
- Fenaux P, Mufti GJ, Hellström-Lindberg E, 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(4):562-569.
- 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):291-299.
- 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.
- Guerra VA, DiNardo C, Konopleva M. Venetoclax-based therapies for acute myeloid leukemia. Best Pract Res Clin Haematol. 2019;32(2):145-153.
- 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.
- Pollyea DA, Altman JK, Assi R, et al. Acute myeloid leukemia, version 3.2023, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2023;21(5):503-513.
- Common Terminology Criteria for Adverse Events. Available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf (Accessed on March 09, 2018).
- García-Delgado R, de Miguel D, Bailén A, et al. Effectiveness and safety of different azacitidine dosage regimens in patients with myelodysplastic syndromes or acute myeloid leukemia. Leuk Res. 2014;38(7):744-750.
- Heiblig M, Elhamri M, Tigaud I, et al. Treatment with low-dose cytarabine in elderly patients (age 70 years or older) with acute myeloid leukemia: a single institution experience. Mediterr J Hematol Infect Dis. 2016;8(1):1-7.
- Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C. Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol. 2015;94(7):1127-1138.
- Babakhanlou R, Ravandi-Kashani F. Non-intensive acute myeloid leukemia therapies for older patients. Expert Rev Hematol. 2023;16(3):171-180.
- Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020; 135(24):2137-2145.
- Kenswil KJG, Pisterzi P, Feyen J, et al. Immune composition and its association with hematologic recovery after chemotherapeutic injury in acute myeloid leukemia. Exp Hematol. 2022;105:32-38.
Details
| Primary Language | English |
|---|---|
| Subjects | Haematological Tumours |
| Journal Section | Research Articles [en] Araştırma Makaleleri [tr] |
| Authors | |
| Publication Date | December 31, 2023 |
| Published in Issue | Year 2023 Volume: 4 Issue: 6 |
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TR DİZİN ULAKBİM and International Indexes (1d)
Interuniversity Board (UAK) Equivalency: Article published in Ulakbim TR Index journal [10 POINTS], and Article published in other (excuding 1a, b, c) international indexed journal (1d) [5 POINTS]
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