AL-05. The efficiency of combination azacitidine and venetoclax therapy in elderly patients at the first-line therapy, and in refractory/relapsed cases of acute myeloid leukemia

Summary

Elderly patients with acute myeloid leukemia (AML) represent a group with a high incidence of poor-prognosis molecular markers as well as with previous myelodysplasia. Due to their age, these cases are associated with high comorbidity which, along with unfavorable recurring genetic anomalies, determines the issues in chemotherapy for such patients [1-3]. Hypomethylating drugs in combination with venetoclax demonstrate relatively high efficacy and a manageable toxicity profile in elderly patients with AML [4]. Our aim was to analyse the efficacy and tolerability of combination therapy with azacitidine and venetoclax (AzaVen) in elderly patients with AML in the first line of therapy, as well as in patients with refractory/relapsed AML (R/R AML).

Materials and methods

The retrospective study included patients with newly diagnosed AML and R/R AML over 60 years old, with contraindications for intensive chemotherapy. The treatment was carried out according to the AzaVen schedule.

Results

The study included 30 patients with newly diagnosed AML older than 60 years, at a median age of 72 years (60 to 90 years old). Cytogenetic data were available for 21 patients, of whom four patients were classified into the high-risk group. One patient was referred to the favorable risk group, and the rest were at intermediate risk. Five patients (17%) had AML associated with prior myelodysplastic conditions. The most frequent comorbidities were as follows: endocrine disorders (20%), diseases of the respiratory system (17%), cardiovascular disorders (63%), tumors of other locations (13%). The median follow-up time was 6.7 months (range, 1.4 to 44.9). The median overall survival (OS) was 38.5 months (Fig. 1). The median OS was not reached if censoring COVID-19-related deaths. In univariate analysis, comorbidity had no effect on OS. By the end of the first cycle of therapy, 18 (60%) patients achieved remission; after the 2^nd cycle, 6 (20%); following the 3^rd and 5^th cycle, one patient each (3%). Remission was defined as complete response (CR), complete response with incomplete recovery (CRi), and morphological remission. CR was registered in 17 patients (56%); CRi, in 4 cases (13%). The overall response rate was 69%. At the current follow-up time, 58.4% of patients maintain a response to therapy. Loss of remission was noted in 3 patients. At 24 months of observation, the OS rate was 88%. The causal structure of mortality in remission state was as follows: 4 cases of COVID-19 (36%), 2 cases of sepsis (18%), and 5 cases with unidentified causes of death (45%) (Fig. 2). The study included 29 patients with R/R AML older than 60 years at the median age of 69 years (60 to 84 years old). In 10 patients (34%), AML was associated with prior myelodysplasia. Cytogenetic data were available in 19 cases and all these patients were at intermediate risk. The most frequent and significant comorbidities were as follows: endocrine diseases (21%), disorders of respiratory system (10%), cardiovascular diseases (57%), tumors at other sites (14%). The median follow-up period was 8.9 months (range 1.3-23.9), and the median OS was 9.3 months (Fig. 3). When censoring deaths related to COVID-19, the median OS is 15.6 months. Comorbidities also did not influence the OS levels. The remission state was achieved in two patients (12%) by the end of the 1^st cycle of therapy; in 8 cases, after 2^nd cycle (47%). The 3^rd, 4^th, 5^th and 6^th cycle of treatment resulted in remission in one patient each (6%). Three patients (18%) achieved remission by the 7^th cycle of therapy. During the observation period, CR was registered in 8 patients (28%), CRi in 7 cases (24%), and morphological remission, in 2 patients (7%). Thus, an overall response was obtained in 15 patients (52%). The median time to loss of response was 5.2 months (Fig. 4). At the current follow-up, only 14% of patients maintained a response to therapy, with OS of 60%.

Conclusion

The results of a retrospective study show high efficacy of the combination of venetoclax and azacitidine in both first-line therapy and R/R AML. Our study demonstrates a high overall survival along with a durable remission period.

Keywords

Acute myeloid leukemia, elderly, venetoclax, azacitidine.