Hematologic Oncology | Ruben A Mesa, MD

Myeloproliferative Neoplasms Update — Part 1: Our interview with Dr Mesa highlights the following topics and cases from his practice: Molecular pathogenesis of myeloproliferative neoplasms (MPNs) (00:00) Cytokine activation and its association with the distinct symptomatology of MPNs (3:42) Targeting the JAK-STAT pathway in myelofibrosis (MF) and polycythemia vera (PV) (5:19) Case:A 66-year-old man with symptomatic primary MF with a CALR mutation receives ruxolitinib (9:05) Clinical parameters to evaluate when considering treatment with ruxolitinib (11:23) Discussing the complexities of allogeneic transplant with patients considering this intervention (16:05) Clinical outcomes and complication rates for younger versus older patients undergoing transplant (16:46) Counseling patients regarding the efficacy and side-effect profile of ruxolitinib (20:41) Symptom improvement with ruxolitinib; dosing for patients with MF (24:14) Management of anemia associated with ruxolitinib treatment (26:27) Approach to dosing ruxolitinib for patients with MF and cytopenias (29:58) Consideration of ruxolitinib treatment holidays and therapy reinitiation for patients with increased splenomegaly (32:22) Treatment options for patients with MF and disease progression on ruxolitinib (36:20) Clonal evolution and outcomes in MF after ruxolitinib discontinuation (38:53) Therapeutic options for patients who experience disease progression on ruxolitinib (41:06) Activity, tolerability and ongoing investigation of novel JAK inhibitors pacritinib, momelotinib and fedratinib in MF (44:36) FDA clinical hold on fedratinib due to possible occurrences of Wernicke encephalopathy in patients on the JAKARTA-1 trial and recent lift of the hold (47:46) Ongoing investigation of fedratinib in MF (48:56) Clinical experience with pacritinib, momelotinib and fedratinib (52:46) Toward identifying molecular predictors of response to pacritinib, momelotinib and fedratinib (53:59) Case: A 64-year-old woman with ruxolitinib-refractory MF receives fedratinib on the Phase II JAKARTA-2 trial (55:51) Therapeutic approach to MF that progresses to acute myeloid leukemia (59:26) Investigation of the novel Bcl-2 inhibitor navitoclax in combination with ruxolitinib for patients with MF (1:2:42) Clinical manifestations and treatment of PV (1:3:12) Case: A 56-year-old woman with high-risk PV and an inadequate response to hydroxyurea receives ruxolitinib (1:5:53) Risk stratification and treatment for patients with essential thrombocythemia (ET) (1:8:26) Select publications