Mesa, Ruben A.

Abstract Myeloproliferative neoplasms (MPN), including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, have a propensity to evolve into accelerated and blast-phase disease (MPN-AP/BP), carrying a dismal prognosis. Conventional antileukemia therapy has limited efficacy in this setting. Thus, MPN-AP/BP is an urgent unmet clinical need. Modest responses to hypomethylating agents and single-agent ruxolitinib have been reported. More recently, combination of ruxolitinib and decitabine has demonstrated synergistic in vitro activity in human and murine systems. These observations led us to conduct a phase 1 study to explore the safety of combined decitabine and dose-escalated ruxolitinib in patients with MPN-AP/BP. A total of 21 patients were accrued to this multicenter study. Ruxolitinib was administered at doses of 10, 15, 25, or 50 mg twice daily in combination with decitabine (20 mg/m2 per day for 5 days) in 28-day cycles. The maximum tolerated dose was not reached. The most common reasons for study discontinuation were toxicity/adverse events (37%) and disease progression (21%). Fourteen patients died during study treatment period or follow-up. The median overall survival for patients on study was 7.9 months (95% confidence interval, 4.1-not reached). Among evaluable patients, the overall response rate by protocol-defined criteria (complete remission with incomplete count recovery + partial remission) was 9/17 (53%) and by intention-to-treat analysis was 9/21 (42.9%). The combination of decitabine and ruxolitinib was generally well tolerated by patients with MPN-AP/BP and demonstrates potentially promising clinical activity. A phase 2 trial evaluating the efficacy of this combination regimen is ongoing within the Myeloproliferative Disorder Research Consortium.

Individualized medicine is important for patients with myeloproliferative neoplasms (MPNs), including essential thrombocythemia, polycythemia vera, and myelofibrosis, which are heterogeneous in terms of genetic mutation profile, prognosis, disease burden, and symptoms. Status of MPN driver mutations in JAK2, CALR, and MPL (or lack of one of these mutations) and other myeloid mutations (ASXL1, SRSF2, CBL, and IDH1/2, among others) affects diagnosis and prognosis. Management begins with estimating the prognosis, disease burden including MPN symptoms, and prevention of vascular events. Allogeneic stem cell transplantation is the definitive therapy in a subset of patients with myelofibrosis, the majority of whom receive JAK inhibition with ruxolitinib to relieve splenomegaly and symptoms and to prolong survival. Ruxolitinib is now a second-line therapy in polycythemia vera, with pegylated interferon being evaluated as a potential front-line therapy compared with hydroxyurea. The therapeutic landscape is evolving to include new JAK inhibitors, which may affect cytopenias (pacritinib and momelotinib), combination therapies including ruxolitinib, and novel targets such as pentraxin and telomerase. Assessing the therapeutic efficacy (including symptom impact) and toxicity of these new approaches is necessary to determine longitudinal management of MPNs in clinical practice and is a key component of “individualizing” care for patients with MPNs.

Myeloproliferative neoplasms (MPNs) are rare hematological malignancies with a significant symptom burden often left unresolved despite recent advances in pharmacological therapy. Yoga is a nonpharmacological strategy that has been shown to improve symptoms in other cancers and may be effective for improving symptoms in MPN patients. Online yoga helps address many of the commonly reported barriers of cancer patients to in-person interventions and may make yoga more accessible to MPNs. An exploration of MPN patient perceptions of participation in online yoga is needed to tailor interventions to patient needs and inform future studies. The purpose of this study was to explore the perceptions of MPN patients participating in a 12-week online yoga intervention. This article represents the combined qualitative interview data from two studies. Participants were asked to complete 60 min/wk of online, home-based yoga and were asked to participate in a 15- to 20-minute phone interview postintervention. The qualitative data was coded in NVivo 11 for content analysis. The total sample included 39 MPN patients. Online yoga was well accepted and liked among these patients. They reported physical (eg, improved sleep, reduced fatigue) and mental (eg, reduced stress) health benefits and liked the convenience of being able to do yoga at home. Online yoga provides a feasible and attractive format through which to deliver a nonpharmacological intervention among MPN patients. Randomized controlled trials are needed to confirm the effects of online yoga on MPN patient symptoms. The qualitative findings presented here help inform the development of these future trials.