Clinical Efficacy of Azacitidine Monotherapy in Elderly Acute Myeloid Leukemia Patients: A Retrospective Analysis from Chennai, India

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Abstract Acute Myeloid Leukemia (AML) predominantly affects older adults, many of whom cannot withstand intensive chemotherapy (IC) regimens. The role of epigenetic dysregulation in AML pathogenesis has led to the use of hypomethylating agents (HMAs) like azacitidine (AZA) as alternative treatment options. This retrospective study evaluates the clinical outcomes of AZA monotherapy in elderly AML patients at MIOT International Hospital, Chennai, India, from 2014 to 2021. We analyzed data from 102 elderly AML patients aged 56-82 who received AZA monotherapy. Patients were given a flat dose of 100 mg AZA daily for 7 days in a 28-day cycle, with a median of nine cycles. The primary endpoints were overall survival (OS), median survival, and treatment response. Secondary endpoints included the proportion of patients transitioning to palliative care after six cycles and the longest duration of survival. Study Design and Patient Population This study retrospectively analyzed 102 elderly AML patients treated with AZA monotherapy at MIOT International Hospital, Chennai, from November 2014 to July 2021. Patients received a flat dose of 100 mg AZA daily for 7 days in a 28-day cycle, with a median of nine cycles administered. Patient Demographics The age range of the patients was 56-82 years, with a median age of 63 years. Patients below 60 years of age who had serious infections at presentation and were unfit for the 7+3 intensive chemotherapy were included. Treatment Outcomes The three-year OS rate was 30.3% (31/102 patients), with a median survival time of 13.2 months. Thirty-six patients (35.3%) who did not respond to therapy after six cycles were transitioned to palliative care. The longest survival duration was 61 months. Six patients below 62 years of age underwent allogeneic transplant consolidation, and eight patients received intermediate-dose cytarabine as consolidation. Oral azacitidine maintenance was not available in India during the study period, but a reduction in the frequency of AZA was tried in good responders. Adverse Events Cytopenias were the most common adverse events, aligning with the known toxicity profile of AZA. No unexpected toxicities were reported. Discussion A large SEER database study looked at 2,263 older adults (age ≥66) with AML treated with first-line HMA, where 51% received AZA. Median survival was 7.1 months compared to 2.7 months without therapy. The inclusion of HMA therapy has expanded options for treating older, unfit AML patients. Our findings align with previous studies indicating that AZA is a viable treatment option for elderly AML patients who are not candidates for intensive chemotherapy. The median survival of 13.2 months and the three-year OS rate of 30.3% are consistent with reported outcomes from similar studies, demonstrating AZA's effectiveness in prolonging survival in this patient population. The transition of 35.3% of patients to palliative care after six cycles underscores the need for early identification of non-responders to adjust therapeutic strategies promptly, especially with the early addition of newer novel combination drugs and targeted agents. Future studies should focus on combining AZA with novel agents to enhance response rates and survival outcomes. Recent years have seen the development of novel AZA-based combination therapies, particularly involving venetoclax, a BCL2 inhibitor. These combinations have shown promising results in clinical trials. Conclusion AZA monotherapy is an effective treatment option for elderly AML patients, offering a median survival of 13.2 months and a three-year OS rate of 30.3% in the pre-venetoclax combination era. These results emphasize the importance of azacitidine and its combination therapy in the therapeutic management of elderly AML patients in the Indian population. References Döhner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med. 2015;373:1136-1152. Estey E, Döhner H. Acute myeloid leukaemia. Lancet. 2006;368:1894-1907. Fenaux P, Mufti GJ, Hellström-Lindberg E, et al. Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomized, open-label, phase III study. Lancet Oncol. 2009;10:223-232. DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naïve, elderly patients with acute myeloid leukemia. Blood. 2019;133:7-17.

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