Maintenance therapy with alternating azacitidine and lenalidomide in elderly AML patients

In a Letter to the Editor of Blood Cancer Journal on 2^nd June 2017, Mathilde Hunault-Berger from Université d'Angers, France and colleagues discussed results from their phase II randomized study (NCT01301820) which aimed to access the tolerance and efficacy of monthly maintenance therapy with alternating azacitidine (AZA) and lenalidomide (LEN) in poor-risk elderly Acute Myeloid Leukemia (AML) patients in First Complete Remission (CR1) after induction chemotherapy.  The study was conducted by the French Innovative Leukemia Organization (FILO).¹

In total, 117 fit elderly AML patients (median age = 69 years) with poor-risk cytogenetics (n = 83) received induction therapy consisting of idarubicin, cytarabine, lomustine and Granulocyte-Colony Stimulating Factor (G-CSF). After induction therapy, sixty-five patients in CR1 received maintenance therapy of 12 cycles of alternating AZA and LEN every 28 days. Patients were randomly assigned to start maintenance therapy either with AZA (arm A, n = 31) or LEN (arm B, n = 34). The primary endpoint of the study was 2-year Disease Free Survival (DFS) improvement of at least 20% compared to historical control.¹

The historical control used in this study was a previous FILO SA-2002 study². This study included seventy-eight poor risk cytogenetics AML patients whom were administered induction therapy followed by a 2 years chemotherapy maintenance.

The key results of the study were:

• Grade 3/4 neutropenia and grade 3 thrombocytopenia were the most common treatment-related Adverse Events (AEs)
• Median DFS in patients with poor-risk cytogenetics in the AZA-LEN and SA-2002 groups; 5.2 vs 6.7 months
• Median Overall Survival (OS) in patients with poor-risk cytogenetics in the AZA-LEN and SA-2002 groups; 8.4 vs 6.6 months

In summary, maintenance therapy with alternating AZA and LEN was tolerable. However, this combination did not improve either DFS or OS compared to the historical control.

The authors highlighted other studies that are combining agents for maintenance therapy. These include the combination of decitabine and clofarabine (NCT01041703) in a phase III study and oral AZA maintenance after daunorubicin- based induction (NCT01757535) in a phase III study. The authors concluded that these combinations “might show a more favorable outcome” in AML patients.