Lenalidomide and Eltrombopag for Treatment of Low- or Intermediate-Risk Myelodysplastic Syndrome: Result of a Phase II Clinical Trial.

PURPOSE: Thrombocytopenia is a serious complication of myelodysplastic syndromes (MDS) associated with an increased bleeding risk and worse prognosis. Eltrombopag (ELT), a thrombopoietin receptor agonist, can increase platelet counts and reverse anti-megakaryopoietic effects of lenalidomide (LEN) in preclinical studies. We hypothesized ELT would reduce the incidence of thrombocytopenia in MDS. PATIENTS AND METHODS: We conducted a Phase II multicenter trial of ELT and LEN in adult patients with low- or intermediate-1-risk MDS with symptomatic or transfusion-dependent anemia or thrombocytopenia (NCT01772420). Thrombocytopenic patients were started on ELT and subsequently treated with LEN after platelets were increased. Patients without thrombocytopenia were started on LEN monotherapy and treated with ELT if they became thrombocytopenic. RESULTS: Fifty-two patients were enrolled; mean age was 71 years (range 34-93). Overall response rate (ORR) in the intention-to-treat population was 35% (18/52). ELT monotherapy led to ORR of 33.3% (7/21), 29% achieving hematologic improvement (HI)-Platelets, and 24% bilineage responses. LEN monotherapy had 38% ORR (6/16) with all responders achieving HI-Erythroid. Fifteen patients received both ELT and LEN with ORR of 33.3%, 20% achieved HI-Erythroid, and 20% HI-Platelets with 13% bilineage responses. Median duration of response was 40 weeks for ELT (range 8-ongoing), 41 weeks (25-ongoing) for LEN, and 88 weeks (8.3-ongoing) for ELT/LEN. Non-hematologic grade 3-4 treatment-related adverse events were infrequent. Among patients on ELT, 2 had major bleeding events, 1 had a reversible increase in peripheral blasts, and 1 developed marrow fibrosis after 6 years on ELT. CONCLUSIONS: ELT and LEN are well tolerated and effective in achieving hematologic improvement in patients with low-/intermediate-risk MDS.

Employer-Funded Complete Health Improvement Program: Preliminary Results of Biomarker Changes.

CONTEXT: Previous studies of the Complete Health Improvement Program (CHIP) have demonstrated short-term improvements in select metabolic and cardiovascular biomarkers in community-based programs. However, less is known about the benefits of an employer-funded lifestyle intervention program. OBJECTIVES: To determine if participation in employer-provided CHIP would result in improvements in short-term metabolic and cardiovascular biomarkers, and to compare the results of the current study to a larger national study. METHODS: This observational study evaluated metabolic and cardiovascular biomarker changes in employer health insurance beneficiaries enrolled in CHIP between August 2012 and November 2014. Body mass index; blood pressure (systolic and diastolic); total cholesterol, low-density lipoprotein, high-density lipoprotein, fasting plasma glucose, and triglyceride levels; and weight were measured at baseline and after CHIP. RESULTS: Of 160 employees enrolled in CHIP, 115 women and 45 men agreed to participate in the study. Overall, the participants demonstrated significant reductions in body mass index, from a baseline average of 31.5 to a post-CHIP average of 30.5 (P<.001), systolic blood pressure from 124.5 to 119.4 mm Hg (P=.017), diastolic blood pressure from 77.3 to 74.5 mm Hg (P=.046), total cholesterol from 186.0 to 168.8 mg/dL (P<.001), low-density lipoprotein from 112.9 to 99.3 mg/dL (P<.001), high-density lipoprotein from 48.8 to 46.4 mg/dL (P<.001), and fasting plasma glucose from 100.8 to 96.5 mg/dL (P<.001). CONCLUSION: When funded by an employer, CHIP demonstrated short-term improvements in select metabolic and cardiovascular biomarkers. Future studies will analyze these data to determine whether these findings translate into subsequent decreased employee absenteeism and reduced beneficiary health claims.