A Phase 1 Study of Concomitant High Dose Lenalidomide and 5-Azacytidine Induction in the Treatment of Acute Myeloid Leukemia,

Abstract 3616 Novel therapies for elderly and relapsed AML are needed. We recently published an institutional phase 2 trial using high dose (50mg/day × 28 days) single agent lenalidomide (HDL) followed by maintenance of 10 mg daily for 12 months in responders in elderly untreated AML patients (≥ 60 years) showing a complete remission (CR)/complete remission with incomplete blood count recovery (CRi) of 30% (Fehniger et al, Blood , 2011). Azacitidine (AZA) given IV or SC has also shown significant response in patients with MDS and AML. Recently Pollyea et al ( JCO 29: 2011 (suppl; abstr #6505) reported on a phase 1 trial combining AZA and escalating doses of lenalidomide repeated sequentially in 6 week cycles in patients with untreated AML. Here, we report on a phase 1 single institutional study to evaluate the toxicities and feasibility of combining HDL and AZA concurrently as induction followed by a less intensive lenalidomide and AZA maintenance schedule in untreated elderly AML (≥60 years) or relapsed/refractory AML ≥18 years. Treatment schedule: 2 cycles of induction (each 28 days) of lenalidomide 50 mg PO days 1–28 and AZA at 3 dose cohorts 25 mg/m2 (cohort 1), 50 mg/m2 (cohort 2) and 75 mg/m2 (cohort 3) given IV days 1–5. Thereafter patients were given maintenance cycles (every 28 days) with lenalidomide 10 mg PO days 1–28 and AZA 75 mg/m2 days 1–5 for a total of 12 cycles. The median age was 74 (range 63–81); 7 males, 8 females; 6 with newly diagnosed elderly AML and 9 with relapsed or refractory AML. The median WBC count was 2600 (range 300–13100). The median bone marrow blast percentage was 22% (range 2–90%),with normal cytogenetics in 7 (63.6%), monosomy 7 in 3 (20%), trisomy 8 in 1 (6.7%), and other in 4 (26.6%). 8 patients were enrolled in cohort 1, 4 patients in cohort 2 and 3 patients in cohort 3. 2 patients in cohort 1 and 1 patient in cohort 2 who received less than 1 induction cycle (2 withdrew consent and 1 had progressive disease) were replaced. 11 (73.3%) of patients completed 1 induction cycle and 7 (46.7%) of patients completed 2 induction cycles and 5 (30%) patients went on to maintenance therapy. Patients remained on therapy for a median of 2 months (range 0.5–13 months). Dose limiting toxicities (DLT) observed included grade 3 rash in cohort 1 leading to expansion of the cohort to include 3 additional patients. To date grade 3/4 non-DLT hematological toxicity was seen in 6/11 (54.1%) patients. The most common 3/4 non-DLT non-hematological toxicity was neutropenic fever seen in 5/11 (45.4%). The most common grade 1/2 toxicity was fatigue in 7/11 (63.6%). 40% (6/15) of patients died, all due to progressive disease. Of the 11 evaluable patients 7 (63.6%) responded to treatment with CR/CRi in 3 (27.3%) and partial remission (PR) in 4 (36.4%) with the median duration of response of 3 months (range 0.5–11 months). In summary combination of lenalidomide with AZA appears to be a feasible regimen with acceptable toxicities. A phase 2 multicenter extension of this study with untreated elderly AML at the maximum tolerated dose of AZA and HDL will be initiated soon. Disclosures: Off Label Use: Here we discuss the use of lenalidomide and azacytidine in relapsed refractory or elderly AML. Stockerl-Goldstein: Celgene: Speakers Bureau. Vij: Celgene: Consultancy, Research Funding, Speakers Bureau.