Combination of hypomethylating agents and inhibitor of BCL-2 in treatment of patients with relapsed acute myeloid leukemia: S.P. Botkin hospital experience
Background. Treatment results in patients with relapsed and refractory acute myeloid leukemia (AML) remain unsatis‑factory. Treatment options for these patients are limited.Aim. To retrospectively analyze the efficacy and safety of combined therapy with hypomethylating agents and venetoclax (VenHMA)...
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ABV-press
2023-03-01
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| Series: | Онкогематология |
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| Online Access: | https://oncohematology.abvpress.ru/ongm/article/view/793 |
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| author | M. A. Granatkin E. A. Nikitin M. I. Kislova E. S. Mikhailov V. A. Doronin S. V. Minenko M. M. Okuneva A. V. Antonova N. V. Degtyareva M. E. Pochtar S. A. Lugovskaya Yu. N. Kobzev V. V. Ptushkin E. V. Rimashevskaya |
| author_facet | M. A. Granatkin E. A. Nikitin M. I. Kislova E. S. Mikhailov V. A. Doronin S. V. Minenko M. M. Okuneva A. V. Antonova N. V. Degtyareva M. E. Pochtar S. A. Lugovskaya Yu. N. Kobzev V. V. Ptushkin E. V. Rimashevskaya |
| author_sort | M. A. Granatkin |
| collection | DOAJ |
| description | Background. Treatment results in patients with relapsed and refractory acute myeloid leukemia (AML) remain unsatis‑factory. Treatment options for these patients are limited.Aim. To retrospectively analyze the efficacy and safety of combined therapy with hypomethylating agents and venetoclax (VenHMA) in patients with relapsed AML and also to compare the results with the cohort of patients who received azacitidine as a monotherapy.Materials and methods. The study included patients with relapsed AML, over 50 years old, who received VenHMA therapy from 01.09.2019 to 01.06.2022 and azacytidine monotherapy from 01.03.2016 to 01.06.2022. In total we identified 38 patients who received VenHMA and 30 patients who received azacytidine alone.Results. The median age of patients in the VenHMA cohort was 66 years (range 51–84). The median number of previous therapy lines was 1.5 (range 1–3), and 12 (32 %) patients had AML evolving from prior myelodysplasia. The median follow-up was 6.2 months, with 20 patients monitored for more than 6 months. Complete response was obtained in 13 (34 %) patients, complete remission with incomplete recovery in 8 (21 %), leukemia-free state in 2 (5 %) patients. Thus, overall response was achieved in 23 (60 %) patients. The median time to achieve overall response was 2.6 months. At the time of the final analysis, 16 patients were still receiving treatment. The median of relapse-free survival in patients with response was not achieved; the median of overall survival was 15.6 months.The groups of patients receiving VenHMA or azacitidine alone were comparable in terms of the main characteristics, with the exception of initial thrombocytopenia <50 × 109/L, which was more frequently encountered in VenHMA cohort (47 % versus 20 %). The median time to the next therapy in the VenHMA group was 10.16 months, in the azacitidine group 6.7 months (hazard ratio (log-rank) 2.02; 95 % confidence interval 1.15–3.5; p = 0.013). The median overall survival in the VenHMA group was 15.6 months, in the azacitidine group 8.5 months (hazard ratio 2.49; 95 % confidence interval 1.36–4,5; p = 0.0044). In a multivariate analysis of factors, associated with adverse outcome (age >65 years, secondary AML, azacytidine monotherapy) only secondary AML was a significant factor for overall survival.Conclusion. The results of our retrospective study show the superiority of the combination regimen of venetoclax and azacitidine in the treatment of AML relapses, both in terms of the quality of remissions and their duration. Patients with relapse and primary refractory AML represent cases of poor cytogenetic prognosis, and have an aggravated somatic status. To date, the use of the VenGMA regimen allows finding the optimal balance between the intensity and toxicity of therapy. |
| format | Article |
| id | doaj-art-ef278213eaf0426fb5eff65766f77a94 |
| institution | DOAJ |
| issn | 1818-8346 2413-4023 |
| language | Russian |
| publishDate | 2023-03-01 |
| publisher | ABV-press |
| record_format | Article |
| series | Онкогематология |
| spelling | doaj-art-ef278213eaf0426fb5eff65766f77a942025-08-20T03:01:02ZrusABV-pressОнкогематология1818-83462413-40232023-03-01181121910.17650/1818-8346-2023-18-1-12-19666Combination of hypomethylating agents and inhibitor of BCL-2 in treatment of patients with relapsed acute myeloid leukemia: S.P. Botkin hospital experienceM. A. Granatkin0E. A. Nikitin1M. I. Kislova2E. S. Mikhailov3V. A. Doronin4S. V. Minenko5M. M. Okuneva6A. V. Antonova7N. V. Degtyareva8M. E. Pochtar9S. A. Lugovskaya10Yu. N. Kobzev11V. V. Ptushkin12E. V. Rimashevskaya13S.P. Botkin City Clinical Hospital, Moscow Healthcare Department; Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaS.P. Botkin City Clinical Hospital, Moscow Healthcare Department; Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaS.P. Botkin City Clinical Hospital, Moscow Healthcare DepartmentS.P. Botkin City Clinical Hospital, Moscow Healthcare DepartmentS.P. Botkin City Clinical Hospital, Moscow Healthcare DepartmentS.P. Botkin City Clinical Hospital, Moscow Healthcare DepartmentS.P. Botkin City Clinical Hospital, Moscow Healthcare Department; Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaS.P. Botkin City Clinical Hospital, Moscow Healthcare DepartmentS.P. Botkin City Clinical Hospital, Moscow Healthcare DepartmentS.P. Botkin City Clinical Hospital, Moscow Healthcare Department; Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaS.P. Botkin City Clinical Hospital, Moscow Healthcare Department; Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaS.P. Botkin City Clinical Hospital, Moscow Healthcare DepartmentS.P. Botkin City Clinical Hospital, Moscow Healthcare Department; Russian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaRussian Medical Academy of Continuing Professional Education, Ministry of Health of RussiaBackground. Treatment results in patients with relapsed and refractory acute myeloid leukemia (AML) remain unsatis‑factory. Treatment options for these patients are limited.Aim. To retrospectively analyze the efficacy and safety of combined therapy with hypomethylating agents and venetoclax (VenHMA) in patients with relapsed AML and also to compare the results with the cohort of patients who received azacitidine as a monotherapy.Materials and methods. The study included patients with relapsed AML, over 50 years old, who received VenHMA therapy from 01.09.2019 to 01.06.2022 and azacytidine monotherapy from 01.03.2016 to 01.06.2022. In total we identified 38 patients who received VenHMA and 30 patients who received azacytidine alone.Results. The median age of patients in the VenHMA cohort was 66 years (range 51–84). The median number of previous therapy lines was 1.5 (range 1–3), and 12 (32 %) patients had AML evolving from prior myelodysplasia. The median follow-up was 6.2 months, with 20 patients monitored for more than 6 months. Complete response was obtained in 13 (34 %) patients, complete remission with incomplete recovery in 8 (21 %), leukemia-free state in 2 (5 %) patients. Thus, overall response was achieved in 23 (60 %) patients. The median time to achieve overall response was 2.6 months. At the time of the final analysis, 16 patients were still receiving treatment. The median of relapse-free survival in patients with response was not achieved; the median of overall survival was 15.6 months.The groups of patients receiving VenHMA or azacitidine alone were comparable in terms of the main characteristics, with the exception of initial thrombocytopenia <50 × 109/L, which was more frequently encountered in VenHMA cohort (47 % versus 20 %). The median time to the next therapy in the VenHMA group was 10.16 months, in the azacitidine group 6.7 months (hazard ratio (log-rank) 2.02; 95 % confidence interval 1.15–3.5; p = 0.013). The median overall survival in the VenHMA group was 15.6 months, in the azacitidine group 8.5 months (hazard ratio 2.49; 95 % confidence interval 1.36–4,5; p = 0.0044). In a multivariate analysis of factors, associated with adverse outcome (age >65 years, secondary AML, azacytidine monotherapy) only secondary AML was a significant factor for overall survival.Conclusion. The results of our retrospective study show the superiority of the combination regimen of venetoclax and azacitidine in the treatment of AML relapses, both in terms of the quality of remissions and their duration. Patients with relapse and primary refractory AML represent cases of poor cytogenetic prognosis, and have an aggravated somatic status. To date, the use of the VenGMA regimen allows finding the optimal balance between the intensity and toxicity of therapy.https://oncohematology.abvpress.ru/ongm/article/view/793acute myeloid leukemiarefractoryrelapsevenetoclaxhypomethylating agents |
| spellingShingle | M. A. Granatkin E. A. Nikitin M. I. Kislova E. S. Mikhailov V. A. Doronin S. V. Minenko M. M. Okuneva A. V. Antonova N. V. Degtyareva M. E. Pochtar S. A. Lugovskaya Yu. N. Kobzev V. V. Ptushkin E. V. Rimashevskaya Combination of hypomethylating agents and inhibitor of BCL-2 in treatment of patients with relapsed acute myeloid leukemia: S.P. Botkin hospital experience Онкогематология acute myeloid leukemia refractory relapse venetoclax hypomethylating agents |
| title | Combination of hypomethylating agents and inhibitor of BCL-2 in treatment of patients with relapsed acute myeloid leukemia: S.P. Botkin hospital experience |
| title_full | Combination of hypomethylating agents and inhibitor of BCL-2 in treatment of patients with relapsed acute myeloid leukemia: S.P. Botkin hospital experience |
| title_fullStr | Combination of hypomethylating agents and inhibitor of BCL-2 in treatment of patients with relapsed acute myeloid leukemia: S.P. Botkin hospital experience |
| title_full_unstemmed | Combination of hypomethylating agents and inhibitor of BCL-2 in treatment of patients with relapsed acute myeloid leukemia: S.P. Botkin hospital experience |
| title_short | Combination of hypomethylating agents and inhibitor of BCL-2 in treatment of patients with relapsed acute myeloid leukemia: S.P. Botkin hospital experience |
| title_sort | combination of hypomethylating agents and inhibitor of bcl 2 in treatment of patients with relapsed acute myeloid leukemia s p botkin hospital experience |
| topic | acute myeloid leukemia refractory relapse venetoclax hypomethylating agents |
| url | https://oncohematology.abvpress.ru/ongm/article/view/793 |
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