Multicenter phase II trial of vitamin K2 monotherapy and vitamin K2 plus 1α-hydroxyvitamin D3 combination therapy for low-risk myelodysplastic syndromes

We performed an open-labeled single-arm prospective phase II clinical trial of vitamin K2 (menatetrenone: VK2) monotherapy and VK2 plus 1α-hydroxyvitamin D3 (alfacalcidol: VD3) combination therapy for myelodysplastic syndromes (MDS) with refractory anemia and refractory cytopenia with multilineage dysplasia, having either low or intermediate-1 risks of the IPSS. The overall response rate to VK2 monotherapy (45 mg/day) after 16 weeks was 13% (5/38) including 4 cases with improvement of both anemia and thrombocytopenia and 1 case with thrombocytopenia. We then enrolled and evaluated 20 out of 33 VK2-monotherapy non-responders for VK2 plus VD3 (0.75 μg/day) combination therapy. The overall response rate at 16 weeks after initiation of VK2 plus VD3 was 30% (6/20). HI for hemoglobin (Hb) was observed in 6 out of 11 patients (55%) and for thrombocytopenia in 3 out of 11 patients (27%), respectively. No HI was observed for neutropenia in VK2 monotherapy and VK2 plus VD3 combination therapy. It was suggested that IPSS scores and absolute neutrophil counts positively correlated, and Hb levels inversely correlated with the response to VK2 plus VD3 combination therapy. Our study demonstrated that VK2 plus VD3 combination therapy appears to be promising for improvement of anemia and thrombocytopenia with low/intermediate-1 MDS.