A Pilot Study of Treatment with Mesterlone, Prednisone and Low-Dose Thalidomide for Patients with Myelodysplastic Syndromes.
Authors: Aguayo Alvaro , Garcia-Alvarez Eunice , Crespo-Solis Erick , Martinez-Banos Deborah , Lopez-Karpovitch Xavier 
Published: November 2019

Myelodysplastic syndromes (MDS) are a group of disorders characterized by ineffective hematopoiesis along with abnormalities in proliferation, differentiation and apoptosis. The overall clinical picture is peripheral cytopenias in the setting of a normocellular or hypercellular bone marrow. A growing body of evidence suggests that angiogenesis has a major role in the pathophysiology of MDS. Androgens promote hemopoiesis by increasing the levels of erithropoietin and stimulate the stem cell compartment of the bone marrow, although rarely effective as a single agent, it is often used clinically. Thalidomide (thali) is an antiangiogenic and immunomodulatory agent that has shown to be active in patients with MDS. In a recent study, prednisone (PDN) increased the tolerability and clinical efficacy of thali in patients with myeloid metaplasia and was used in the past in patients with MDS. The purpose of this study was to prospectively evaluate response to the combination of Thali-mesterolone (MRL)-PDN by using the International Working Group Criteria of Response in MDS, in a cohort of patients with transfusion-dependent MDS (TD-MDS). Protocol was approved by the Institutional Ethics Committee, was conducted according to the Helsinki declaration, and an informed consent was signed by all participants.

Results: From April 2002 to February 2007, 15 patients have been consecutively treated with thali 100 mg/d, MRL 150 mg/d and prednisone starting at 50 mg/d with further, slow tapering over 3 months. Seven (46.7%) males, median age was 59 years (range 36–78) and WHO-MDS as follows: refractory cytopenia with multilineage dysplasia (RCMD) 9/15 (60%); 5q- syndrome 1/15 (6.6%), refractory anemia with excess of blasts (RAEB)-1 2/15 (13.3%), RAEB-2 (13.3%), and unclassified MDS 1/15 (6.6%). Ten patients (66.7%) had received previous therapy for MDS. Good cytogenetic (CG) risk was present in 10 pts (66.7%); 3/15 (20%) had intermediate risk CG, and 2 (13.3%) patients had no metafases to analyze at diagnosis. Intention-to-treat (ITT) analysis after a 6-months period of therapy showed 2/15 (13.3%) complete response (CR); 2/15 (13.3%) major hematologic response (MHR), and 4/15 (26.7%) a minor hematologic response. There was a decrease in the transfusion-dependence in 3/15 patients (20%); 4/15 (26.7%) patients did not decreased their transfusion-dependence, and 3 of them had progresion to acute leukemia. Adverse events where mild (grade 1–2), easily handled, and included 53% of patients with peripheral neuropathy, 40% had headhache, 33% reported frequent infections, and 1 patient had asymptomatic bradycardia that subsided with thali withdrawal. At the last follow-up, 3 patiens progressed to acute leukemia and died. Median survival of the group is 15.2 months (range 1–50.2). Two of the patients presented here where included in the ITT analysis and where part of the patients that did not responded to therapy and died from progression to acute leukemia.

Conclusions: The combination of Thali-MRL-PDN is active in TD-MDS, however new options of therapy are needed to treat this subset of patients, specially in countries where lenalidomide, decitabine and 5-azacitidine are not available yet.