Characteristics and Role of Lenalidomide Therapy in Patients with Myelodysplastic/Myeloproliferative Neoplasm with Ring Sideroblasts and Thrombocytosis
Authors: Naqvi Kiran , Sasaki Koji , Montalban-Bravo Guillermo , Teach Michael S , Pierce Sherry A. , Kantarjian Hagop M. , Garcia-Manero Guillermo 
Published: October 2019

Abstract
Introduction:
Myelodysplastic/Myeloproliferative neoplasm with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T), previously known as RARS-T is now recognized as a full entity in the 2016 World Health Organization classification of myeloid neoplasms and acute leukemia. It is characterized by thrombocytosis (>=450 x 109/L), refractory anemia, with dyserythropoiesis in the bone marrow with >=15% ringed sideroblasts, and megakaryocytes with features resembling those in myelofibrosis or essential thrombocythemia. Currently there are no formal guidelines for the management of this disease. Lenalidomide has been described in case reports to have clinical activity in this rare disorder. Here we describe the disease characteristics and efficacy of lenalidomide in patients with MDS/MPN-RS-T.
Methods:
We reviewed the records of 53 patients with MDS/MPN-RS-T that presented to MD Anderson Cancer Center since 2000. Of these, we identified 7 patients that were confirmed to have MDS/MPN-RS-T and were treated with lenalidomide. In addition to the demographic data, we also collected information on cytogenetics, the international prognostic scoring system (IPSS) and the mutational status including JAK2, MPL, CALR and SF3B1. We also collected data on thrombosis and cardiovascular risk factors.
Results:
Seven patients were noted to have MDS/MPN-RS-T, of which 4 were male and 6 were white. All 7 patients were categorized as lower risk MDS by the IPSS (4 had low risk disease, 3 had intermediate 1). Five of the 7 patients had a diploid karyotype while 1 patient had del 11q and 1 had inversion 3q21. Median platelet count was 713 x 109/L (range 462-993), median hemoglobin was 10 gm/dl (range 8.3-11.3) and median white blood cell count was 9.7 x 109/L (range 4.5-24). Five of the seven patients (71%) harbored a JAK2V617F mutation, 1 harbored MPL. Only 2 patients were noted to have a SF3B1 mutation while testing was not available for the remaining 5 patients. Three patients that had CALR testing done were all negative for the mutation. Two patients were noted to carry an ASXL1 mutation. Two patients had coronary artery disease prior to being diagnosed with MDS/MPN-RS-T. Of these 1 patient also had pulmonary embolism prior to being diagnosed, while the other patient had deep vein thrombosis after diagnosis. Median time from diagnosis to treatment was 12.4 months (range 2.1-47.4). Median number of prior therapies was 1 (range 0-3). Three patients received lenalidomide frontline therapy. Overall, 3/7 patients (43%) responded to lenalidomide therapy. Four patients were red cell transfusion dependent at the time of lenalidomide initiation. Of these half became transfusion independent. Of the 3 patients that were transfusion independent at lenalidomide initiation, 1 responded with improvement in counts, 1 showed no hematological improvement, while 1 patient stopped therapy after 2 cycles due to rash. Of the patients with no hematological improvement to lenalidomide, all 3 patients had overall stable disease and good tolerance to therapy. Only 1 patient achieved molecular remission. None of the 2 patients carrying the ASXL1 mutation, and patient with inversion 3q21 responded to lenalidomide therapy. Median time on lenalidomide therapy was 14 months (3-30). Only 1 patient has died while none of the patients transformed to acute leukemia. Median overall survival has not been reached.
Conclusion:
MDS/MPN-RS-T, a recently approved WHO entity, has no consensus on optimal treatment and response criteria. Lenalidomide in our study shows clinical activity with improvement in counts and achieving transfusion independence. Also noted is stabilization of counts in those who fail to achieve a hematological improvement. We need to further explore its role in MDS/MPN-RS-T in larger clinical trials.

Disclosures
Sasaki: Otsuka Pharmaceutical: Honoraria.