LOW-DOSE LENALIDOMIDE COUPLED with LOW-DOSE Cytarabine INDUCES COMPLETE REMISSION of Elderly ACUTE Myeloid LEUKEMIA PATIENTS with Unfavorable Citogenetics: PRELIMINARY RESULTS of A PHASE II STUDY,

Abstract 3627

We designed a phase II study to assess the antitumor efficacy of the combination regimen with low-dose lenalidomide and low-dose cytarabine in patients with acute myeloid leukemia (AML) aged >70 years. Twenty-one patients (median age 76 years, range: 70–80) were consecutively enrolled in the study. Median white blood cell count at diagnosis was 11.920 x10⁹/l (range: 0.59–46.8×10⁹/l), whereas median haemoglobin was 8.9 g/dl and median platelet count was 30×10⁹/l. Four out of 21 patients had a normal karyotype, whereas 17/21 presented with an intermediate or unfavourable karyotype. Twelve patients had a de novo AML, whereas 9 patients had a secondary AML (5 after MDS, 1 after a CMPD, 1 after myelofibrosis, 2 after chemo-radiotherapy for a breast cancer). All patients received low-dose lenalidomide (10 mg/day orally, days 1–21) and low-dose cytarabine (20mg twice day subcutaneously, days 1–15). Therapy was repeated every 6 weeks, up to 6 cycles. Six out of 21 patients died in aplasia while receiving the first induction cycle of therapy, and are not evaluable for response. One patients is still completing the first cycle. Fourteen patients completed at least one cycle of therapy and are evaluable for response. Among these patients, 8/14 (57%) cleared peripheral blood blasts at the end of the second week of the first cycle, with recovery of normal WBC, hemoglobin and platelets values after a median of 31 days (range: 27–42) from the start of chemotherapy. Six out of 8 responding patients are still in morphologic, cytogenetic and FISH CR after 14, 12, 10, 7, 3 and 3 months from the start of therapy, respectively. Two patient died while in CR after receiving, respectively, the second and the third cycle of therapy due to a multi organ failure after an infectious complication. The other 6 patients who completed at least one cycle of therapy did not respond at all and rapidly died due to progressive disease. At present, out of 8/14 (57%) patients evaluable for response that obtained CR, 6/14 (42%) are alive in continuous CR and two died in CR. Notably, all responding patients presented with low blast count and unfavorable cytogenetics at diagnosis.

In conclusion, low-dose lenalidomide has clinical activity, when coupled with low-dose cytarabine, in an extremely poor-prognosis subset of AML. Considering the scarce compliance of elderly, frail AML patients to high-dose therapy, the low dose schedule could be particularly profitable, specially for patients with low blast count and unfavorable cytogenetics. The study was registered at EMA with the EUDRACT no 2008–006790–33.