Azacitidine and Lenalidomide Combination In Higher-Risk Myelodysplastic Syndromes-Preliminary Results Of The Vilen-01 Protocol

Hypomethylating agents are the standard therapy for higher-risk (HR, Int-2 and high-risk) myelodysplastic syndromes (MDS). Lenalidomide is effective in lower-risk (LR) MDS, with or without 5q-, in HR-MDS and in acute leukemia. Many patients remain resistant to a single agent. A potential synergistic effect of both agents has been shown [Sekeres M et al, Am J Hemat 2010; Blood 2012]. Thus, the MDS Israel group has designed a phase II clinical trial (NIH trial #: TASMC-10-MM-0437-09-CTIL).

The ViLen-01 protocol consists of 3 phases. The induction phase includes 6 monthly cycles of SC azacitidine (Aza), 75 mg/m daily, days 1-5, and PO lenalidomide (Len) 10 mg daily, days 6-21, followed by a 7-day (days 22-28) respite. The consolidation consists of 6 monthly cycles of Aza only for 5 days each, followed by 12 months of maintenance with Len only. Response is evaluated by the IWG criteria [Cheson B et al, Blood 2006].

As of July 2013, 7 medical centers have enrolled 18 patients. Patients had been diagnosed with either HR-MDS, or LR-MDS with transfusion-dependence, erythropoietin resistance and poor cytogenetics. Adverse events (AE) were as expected in these elderly HR-MDS patients. The common AEs were grade IV transient cytopenias, requiring dose modification in 15 patients. Only 2 patients stopped the protocol due to AE. Thirteen patients completed the induction, 8 continued to consolidation, and 5 patients continued to maintenance. Eight of the 18 enrolled patients (44%, 8 of the 13, 61.5%) who had completed the induction, achieved CR. Three of the 8 patients in CR also attained cytogenetic response. The other 5 had normal karyotype on study initiation. Five other patients obtained erythroid response and became transfusion-free, and another patient achieved platelet response, for a total of 14 (78%) responders. It is still too early to evaluate response duration and survival. One patient is in early induction, and 4 are still being treated. The others have either died or have discontinued for various reasons (patient refusal, progressive disease, transplant).

These preliminary data in a small group of patients with HR-MDS and expected poor prognosis, demonstrate a high response rate and a reasonable safety profile. The study is ongoing. If these results are confirmed in randomized trials, it may set new standards for the treatment of this disease.

No relevant conflicts of interest to declare.