A Phase II Study of High Dose Lenalidomide as Initial Therapy for Acute Myeloid Leukemia in Patients > 60 Years Old.

AML pts over the age of 60 years (AML ≥ 60) have a poor prognosis and warrant novel therapeutic approaches. Lenalidomide used at the approved starting dose of 10mg/day, with dose reductions for neutropenia/thrombocytopenia, has been shown to produce clinically significant unilineage erythroid responses in pts with myelodysplastic syndromes. However, even in these trials lenalidomide was shown to reduce the bone-marrow blasts. We hypothesized that using a higher potentially myelosuppressive fixed dose for induction therapy may be active in the therapy of AML ≥ 60 yrs.

Eligibility criteria: untreated AML ≥ 60 with intermediate- or poor-risk cytogenetics (chromosome 5q- excluded), ECOG PS 0-2, and adequate organ function. Treatment included 2 cycles of high dose lenalidomide (50 mg/day) x 28 days (induction), followed by low dose lenalidomide (10 mg/day) × 28 days for an additional 12 months in non-progressing pts. The primary endpoint was complete remission (CR), including cytogenetic complete remission (CRc), morphologic complete remission (CRm) and complete remission with incomplete blood count recovery (CRi).

33 pts were enrolled in this cohort, with a median age of 71 (range 60-88) years. 21 pts (64%) had intermediate risk and 12 (36%) poor risk cytogenetics. 23 pts (70%) had de novo AML and 10 pts (30%) had AML transformed from MDS/secondary to prior therapy. Median peripheral WBC at presentation was 4200 (range 600-44,000)/mm³. Median duration on therapy was 64 (range 3-267) days. Median follow-up from time of enrollment was 143 (range 6-401) days. In the intent-to-treat (ITT) population CR has been observed in 30%(10/33) and includes 3 CRc, 2 CRm, and 5 CRi. 45% (10/22) pts completing the entire 56 day induction regimen and 50% (10/20) pts with a presenting circulating blast count <1000/mm³ achieved CR. Responses were rapid with two pts confirmed to be in CR on day 15, five additional pts on day 28 and the 3 remaining pts on day 56. For the 7 pts that achieved a CR and had a clonal cytogenetic abnormality at diagnosis, 6 pts had resolution of the cytogenetic abnormality at the time of CR. Median CR duration was 5 (range 1 to ≥ 8) months, with 4 pts in CR currently remaining on low dose therapy at >8, >7, >7, and >4 months after achieving remission. No pt experienced bone-marrow aplasia according to biopsies performed on days 15, 28 and 56 of induction therapy. Median days of hospitalization were 6 (range 0-40). Reasons for treatment discontinuation were disease progression in 61%(20/33) and adverse events in 24%(8/33) and patient preference in 3% (1/33). The 60 day mortality was 27% (9/33) with 7 of these deaths due to disease progression. Treatment associated Grade (Gr) 3-4 hematologic toxicities included thrombocytopenia (67%), anemia (55%) and neutropenia (33%). Gr 3-4 febrile neutropenia occurred in 27%, pneumonia in 24% and bacteremia in 24%. Other Gr 3-4 non-hematologic toxicities in >10% of patients included fatigue (15%) and hypoxia (15%).

High dose single agent lenalidomide represents a novel and effective therapeutic option with rapid onset of responses in older AML patients. Additional studies are needed to better understand the mechanism whereby lenalidomide induces CR in AML.

Vij:CELGENE: Honoraria, Research Funding, Speakers Bureau. Off Label Use: LENALIDOMIDE IN ACUTE MYELOID LEUKEMIA. Fehniger:CELGENE: Research Funding.