Pilot Study of Sorafenib for Myelodysplastic Syndrome

MDS (Myelodysplastic syndrome) is a hematologic malignancy in which one or multiple conditions affects the fabrication (or dysplasia) of the myeloid class of blood cells. While treatable, therapies provide short term benefit and are not considered curable, short of an allogeneic stem cell transplant. The RAS pathway has been noted to be abnormally regulated in many malignancies, including MDS and AML. Thus, we performed a phase 2 efficacy study using sorafenib, a RAS inhibitor, for patients with MDS by WHO criterion.

Adults with primary or secondary MDS, estimated CrCl >30 ml/min, and liver function tests ² 2. 5 × ULN were eligible. Patients of all IPSS risk categories were included. Patients received Sorafenib 400mg po bid daily for 28 days for a 28 day cycle (continuous therapy) and continued till progression or withdrawal for toxicity. Patients were evaluated after the first 2 cycles for response and then every 3 cycles thereafter until an endpoint was reached (up to five years).

Patient and disease characteristics are noted in the table below. Sixteen evaluable patients were treated on study: median 71 (range 56–88 years), median time from diagnosis to starting this study was 34 months (range 9–103 months), median number of prior therapies was 2 (range 0–6), median number of cycles on study was 1. 5 (range 1–7). Responses lasted for 4 months in 4 and a year in 1.

The agent was tolerated in this population though some toxicities were notable: 2 (12%) had grade 2 rash (though many with grade 1), 5 with grade 2 (31%) and 1 (6%) grade 3 nausea, vomiting or diarrhea, 2 (12% with grade 2 and 1 (6%) with grade 3 liver function abnormalities, and 1 (6%) grade 4 myositis likely related to the agent. Unfortunately, many of the toxicities occurred shortly after initiating therapy, leading to early withdrawal from therapy before a full cycle and evaluation for response could be performed.

Sorafenib was tolerated and provided some responses in this difficult to treat group of unselected patients. Due to many early withdrawals, the study was terminated early. Utility would be enhanced in future studies by devising methods to apriori select this targeted therapy for those most likely to respond.

No relevant conflicts of interest to declare.