İntensif Tedaviye Uygun Olmayan Akut Myeloid Lösemi Hastalarında Hipometilleyici Ajan Venetoklaks Kombinasyonu Sonuçlarının Değerlendirilmesi

Year 2024, Volume: 46 Issue: 2, 275 - 283, 18.03.2024

Tuğcan Alp Kırkızlar , Ahmet Muzaffer Demir

https://doi.org/10.20515/otd.1436206

Abstract

Ortanca tanı yaşı 68 olan akut myeloid lösemide (AML) intensif tedavi adayı olamayan ileri yaş grubunda sağkalım süresi belirgin olarak düşüktür. Günümüzde bu hasta grubu için standart tedavi haline gelen hipometilleyici ajan-venetoklaks (HMA-V) kombinasyonuyla sağkalım süresi ve yaşam kalitesi artmıştır. Biz de merkezimizde intensif tedaviye uygun olmayan AML hasta grubunda HMA-V kombinasyon tedavisi sonuçlarını incelemeyi amaçladık. Çalışmaya dahil edilen 37 hastanın ortanca yaşı 70.2 yıl ve %51.4’ ü kadın idi. Hastaların %73’ü de novo lösemi olup 4 hasta nüks, 1 hasta azasitidin sonrası refrakter hastalıktı. Remisyon sağlanan 2 hastaya intensif tedavi intoleransı/yan etkisi nedeniyle HMA-V kombinasyonu verildi. Azasitidin kullanım oranı %78.6 idi. Ortanca kurs sayısı 3 idi. 1. veya 2. kurs sonunda kemik iliği değerlendirmesinde remisyon oranı %51.4 olarak bulundu. Ortalama izlem süresi 11.9 ay olup hastaların %56.75’i hayatını kaybetti. Sağkalım analizlerinde ortalama ve ortanca yaşam süreleri 18 ve 13 ay olarak saptandı. Ortalama yaşam süreleri remisyon sağlananlarda, sağlanamayanlarda ve değerlendirilemeyenlerde sırasıyla 27.1, 4.1 ay ve ve 7.5 ay idi ve gruplar arasında anlamlı farklılık saptandı (p <0.001). Azasitidin ile ortalama ve ortanca yaşam süreleri 22.03 ve 23 ay iken, desitabin ile bu süreler sırasıyla 3.87 ve 3 ay idi ve belirgin istatiksel farklılık mevcuttu (p <0.001). Cox regresyon multivariate analizinde mortalite üzerinde etkili tek faktör 1./2. siklus sonu değerlendirmesinde remisyonda olmamak olarak bulundu (p 0.004). Sonuç olarak, merkezimizin sağkalım ve remisyon oranları gerçek yaşam çalışmalarıyla benzer olarak bulunmuştur.

Keywords

akut myeloid lösemi, azasitidin, desitabin, venetoklaks

Evaluation Of Hypomethylating Agent Venetoclax Combination In Patients With Acute Myeloid Leukaemia Ineligible For Intensive Treatment

Abstract

: In acute myeloid leukaemia (AML), which the median age at diagnosis is 68 years, survival is significantly lower in the elderly group who are ineligible for intensive treatment. Survival and quality of life have been improved with the combination of the hypomethylating agent venetoclax (HMA-V), which has become the standard of care for this group of patients. We aimed to evaluate the results of HMA-V combination therapy in the group of AML patients who are ineligible for intensive treatment at our centre. The median age of the 37 patients included in the study was 70.2 years, and 51.4% were women. 73% of the patients were de novo leukemia while 4 patients were relapse and 1 was refractory disease. The HMA-V combination was given 2 patients who were in remission due to intolerance/side effects of intensive treatment. Azacitidine usage rate was 78.6%. The median number of course was 3. The remission rate was found to be 51.4% in bone marrow evaluation at the end of the 1st/2nd course. The mean follow-up was 11.9 months and 56.75% of patients died. Mean survival was 27.1, 4.1 and 7.5 months for those who achieved remission, those who did not achieve remission and those who could not be assessed, respectively, with a significant difference between groups (p <0.001). While mean and median survival with azacitidine were 22.03 and 23 months, with decitabine 3.87 and 3 months respectively, there was a significant statistical difference (p<0.001). In multivariate Cox regression analysis, the only factor influencing mortality was not being in remission at the end of 1st/2nd cycle assessment. In conclusion, the survival and remission rates seen in our center are found to be similar to real-world studies.

Keywords

acute myeloid leukemia, azacitidine, decitabine, venetoclax

References

• 1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA: A Cancer J Clin 2020; 70(1):7–30.
• 2. Estey EH. Acute myeloid leukemia: 2019 update on risk-stratification and management. Am J Hematol 2018; 93(10):1267–1291.
• 3. Newell LF, Cook RJ. Advances in acute myeloid leukemia. BMJ 2021;375:n2026.
• 4. Ucciero A, Pagnoni F, Scotti L, et al. Venetoclax with hypomethylating agents in newly diagnosed acute myeloid leukemia a systemic review and meta-analysis of survival data from real-world studies. Cancers 2023; 15(18):4618.
• 5. Juliusson G. Older patients with acute myeloid leukemia benefit from intensive chemotherapy: An update from the Swedish Acute Leukemia Registry. Clin Lymphoma Myeloma Leuk 2011; 11(1):54-59.
• 6. Döhner H, Estey E, Grimwade D, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an International Expert Panel. J Am Soc Hematol 2017; 129(4):424–447.
• 7. 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.
• 8. De Bellis E, Imbergamo S, Candoni A, et al. Venetoclax in combination with hypomethylating agents in previously untreated patients with acute myeloid leukemia ineligible for intensive treatment: A real-life multicenter experience. Leuk Res 2022; 114:106803.
• 9. Todisco E, Papayannidis C, Fracchiolla N, et al. AVALON: The Italian cohort study on real-life efficacy of hypomethylating agents plus venetoclax in newly diagnosed or relapsed/refractory patients with acute myeloid leukemia. Cancers 2023; 129(7):992–1004.
• 10. Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40(5):373-83.
• 11. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 2016; 127(20):2391-2405.
• 12. 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.
• 13. DiNardo CD, Tiong IS, Quaglieri A, et al. Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML. Blood 2020; 135(11):791–803.
• 14. Morsia E, McCullough K, Joshi M, et al. Venetoclax and hypomethylating agents in acute myeloid leukemia: Mayo clinic series on 86 Patients. Am J Hematol 2020; 95(12):1511–1521.
• 15. Pollyea DA, Pratz K, Letai A, et al. Venetoclax with azacitidine or decitabine in patients with newly diagnosed acute myeloid leukemia: Long term follow-up from a phase 1b study. Am J Hematol 2020; 96(2):208–217.
• 16. Winters AC, Gutman JA, Purev E, et al. Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia. Blood Adv 2019; 3(20):2911–2919.