Azacitidine Plus Lenalidomide for Untreated AML Patients Ineligible for Conventional Chemotherapy

Abstract ³⁵⁷⁵

There are limited treatment options for older patients with acute myeloid leukemia (AML) and prognosis has remained poor, thereby warranting development of novel therapeutic strategies. The optimal treatment for these patients requires the consideration of multiple factors, such as patient and disease-related factors that can help to determine the appropriate therapy. Previous studies have shown that both azacitidine and lenalidomide have single-agent activity in patients older than 60 years with untreated AML and have non-overlapping mechanisms of action that may complement each other. We evaluated the efficacy and safety of the combination of azacitidine plus lenalidomide as front-line therapy for untreated, older AML patients. In this phase 2 study, patients 60 years of age or older with untreated AML received azacitidine 75mg/m² for 7 days followed by escalating doses of lenalidomide daily for 21 day on 42-day cycles. Patients received continued therapy until disease progression, an unacceptable adverse event, or completion of 12 cycles. Forty-one AML patients (median age, 74 years) were enrolled with equal distribution according to ELN risk. Overall response rate (ORR) was 41% (CR/CRi rate was 29%). The median time to CR/CRi was 12 weeks, and duration of CR/CRi was 28 weeks (range, 4- >104 weeks). The median OS was 20 weeks (range, 1–121+) for the entire cohort and 69 weeks (range, 10–121+) for responders (Figure 1A; responders had better OS compared to non-responders (69 vs. 15 weeks, p-value <0.01). Baseline characteristics, such as age at diagnosis, baseline WBC count, bone marrow blast percentage or ELN risk classification, or molecular markers were not predictive of responses. Overall survival was similar according to ELN classification. Therapy-related AML and high hematopoietic cell transplantation comorbidity index were the only negative predictors of response. Early death was noted in 14% of patients. Grades ≥ 3 toxicities were uncommon and most adverse events were gastrointestinal, fatigue and myelosupression. Sequential combination of azacitidine plus lenalidomide has evidence of clinical activity as initial therapy for older AML patients, and further study of this combination in AML and MDS is warranted. This study is registered at www.clinicaltrials.gov as # NCT00890929.