Combination Azacitidine and Lenalidomide: A Novel Relapse Prophylaxis Option in Patients after Allogeneic Stem-Cell Transplantation for Acute Myeloid Leukemia

Introduction: Some patients with acute myeloid leukemia (AML) will still relapse after receiving allogeneic hematopoietic stem cell transplantation (allo-SCT). Once relapse, the salvage options are limited and difficult. Therefore, novel drug regimens to prevent relapse after transplantation are required.

Both azacitidine (AZA) and lenalidomide (LEN) possess significant antitumor activity effect in myeloid neoplasms. LEN as maintenance or pre-emptive therapy in the first 3 months post-transplantation was reported to induce severe graft-versus-host disease (GVHD), but AZA has been shown to ameliorate GVHD in transplantation. We therefore examined the efficacy and safety of combined AZA/LEN prophylactic regimen after transplantation.

Patients and Methods: AML patients who had received allo-SCT were treated with AZA (75 mg/m² for 7 days) followed by low dose of LEN on days 10 to 28. The above is one cycle, a total of 8-10 cycles. The course of treatment can be appropriately changed according to the patient's tolerance and condition. The primary endpoint is cumulative incidence of relapse (CIR), the secondary endpoints are Overall survival (OS), Disease-free survival (DFS), adverse events (AEs).

Results: A total of 28 patients received azacytidine and low-dose lenalidomide prophylaxis after allo-SCT. According to risk stratification, 71% (20/28) patients were at high risk and 29% (8/28) were at intermediate risk. Median chemotherapy numbers before transplantation were 4 (3-8) cycles. The transplantation model includes Haplo-identical (46%), HLA-identical sibling (14%), and Unrelated donor (40%). With a median follow-up of 387 (94-1073) days, 9 patients relapsed (including molecular relapse and cytological relapse), among them, 4 patients had molecular relapse and MRD was changed into negative again after treatment with this AZA/LEN regimen, and other 5 patients developed cytologically relapsed, so this program was terminated, and they received new treatment, but all still alive now. The remaining 23 have survived so far, with disease free. The 1-year CIR is 26 %, and 2-year CIR is 41 %. The 1-year DFS is 74%, and the 2-year DFS is 59%. OS is 100%. Sequential AZA and LEN prophylaxis therapy was well tolerated. About adverse events: a total of 8 patients had grade 3-4 neutropenia, none had agranulocytosis with fever; 3 patients had grade 3-4 thrombocytopenia; Grade 3 transaminase elevations occurred in 2 patients. Four patients developed chronic GVHD after AZA/LEN regimen with a score of 1-2, and no patient developed acute GVHD.

No relevant conflicts of interest to declare.