Patients who develop steroid-refractory acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation have poor prognosis, highlighting an unmet therapeutic need. In this open-label phase 2 study (ClinicalTrials.gov identifier: NCT02953678), patients aged at least 12 years with grades II to IV steroid-refractory aGVHD were eligible to receive ruxolitinib orally, starting at 5 mg twice daily plus corticosteroids, until treatment failure, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) at day 28; the key secondary end point was duration of response (DOR) at 6 months. As of 2 July 2018, 71 patients received at least 1 dose of ruxolitinib. Forty-eight of those patients (67.6%) had grade III/IV aGVHD at enrollment. At day 28, 39 patients (54.9%; 95% confidence interval, 42.7%-66.8%) had an overall response, including 19 (26.8%) with complete responses. Best ORR at any time was 73.2% (complete response, 56.3%). Responses were observed across skin (61.1%), upper (45.5%) and lower (46.0%) gastrointestinal tract, and liver (26.7%). Median DOR was 345 days. Overall survival estimate at 6 months was 51.0%. At day 28, 24 (55.8%) of 43 patients receiving ruxolitinib and corticosteroids had a 50% or greater corticosteroid dose reduction from baseline. The most common treatment-emergent adverse events were anemia (64.8%), thrombocytopenia (62.0%), hypokalemia (49.3%), neutropenia (47.9%), and peripheral edema (45.1%). Ruxolitinib produced durable responses and encouraging survival compared with historical data in patients with steroid-refractory aGVHD who otherwise have dismal outcomes. The safety profile was consistent with expectations for ruxolitinib and this patient population.
BackgroundThe Philadelphia chromosome−negative myeloproliferative neoplasms (MPN) myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) negatively affect patient quality of life (QoL) and are associated with increased risk of mortality.MethodsThe MPN Landmark survey was conducted from May to July 2014 in patients with MF, PV, or ET under active management in the United States. The survey assessed respondent perceptions of disease burden and treatment management and included questions on overall disease burden, QoL, activities of daily living, and work productivity. Outcomes were further analyzed by calculated (ie, not respondent-reported) prognostic risk score and symptom severity quartile.ResultsThe survey was completed by 813 respondents (MF, n = 207; PV, n = 380; ET, n = 226). The median respondent age in each of the 3 MPN subtypes ranged from 62 to 66 years; median disease duration was 4 to 7 years. Many respondents reported that they had experienced MPN-related symptoms ≥1 year before diagnosis (MF, 49 %; PV, 61 %; ET, 58 %). Respondents also reported that MPN-related symptoms reduced their QoL, including respondents with low prognostic risk scores (MF, 67 %; PV, 62 %; ET, 57 %) and low symptom severity (MF, 51 %; PV, 33 %; ET, 15 %). Many respondents, including those with a low prognostic risk score, reported that their MPN had caused them to cancel planned activities or call in sick to work at least once in the preceding 30 days (cancel planned activities: MF, 56 %; PV, 35 %; ET, 35 %; call in sick: MF, 40 %; PV, 21 %; ET, 23 %).ConclusionsThese findings of the MPN Landmark survey support previous research about the symptom burden experienced by patients with MPNs and are the first to detail the challenges that patients with MPNs experience related to reductions in activities of daily living and work productivity.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2208-2) contains supplementary material, which is available to authorized users.
BACKGROUNDThis analysis of the myeloproliferative neoplasm (MPN) Landmark survey evaluated gaps between patient perceptions of their disease management and physician self‐reported practices.METHODSThe survey included 813 patient respondents who had MPNs (myelofibrosis [MF], polycythemia vera [PV], or essential thrombocythemia [ET]) and 457 hematologist/oncologist respondents who treated patients with these conditions.RESULTSGreater proportions of physician respondents reported using prognostic risk classifications (MF, 83%; PV, 59%; ET, 77%) compared with patient recollections (MF, 54%; PV, 17%; ET, 31%). Most physician respondents reported that their typical symptom assessments included asking patients about the most important symptoms or a full list of symptoms, whereas many patient respondents reported less specific assessments (eg, they were asked how they were feeling). Many patient respondents did not recognize common symptoms as MPN‐related. For example, approximately one‐half or more did not believe difficulty sleeping resulted from their MPN (MF, 49%; PV, 64%; ET, 76%). Physician respondents underestimated the proportion of patients who had symptomatic PV or ET at diagnosis compared with patient respondents. There was discordance regarding treatment goals: among patient respondents with MF or PV, “slow/delay progression of condition” was the most important treatment goal, whereas physician respondents reported “symptom improvement” and “prevention of vascular/thrombotic events,” respectively. Finally, more than one‐third of patient respondents were not “very satisfied” with their physician's overall management/communication.CONCLUSIONSThe care and satisfaction of patients with MPN may be improved with increased patient education and improved patient‐physician communication. Cancer 2017;123:449–458. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoeitic disorders characterized by ineffective hematopoiesis and potential transformation to acute myeloid leukemia (AML). For decades, the mainstay of treatment for MDS was supportive care, including transfusion of blood products and growth factors. Further understanding of disease biology led to the discovery of a high prevalence of hypermethylation of tumor suppressor genes in high-risk MDS and secondary leukemias. Hence, the role of irreversible DNA methlytransferase inhibitors such as azacitidine was investigated with promising outcomes in the treatment of MDS. Azacitidine was initially approved in the USA by the Food and Drug Administration (FDA) in 2004 for the treatment of all subtypes of MDS and was granted expanded approval in 2009 to reflect new overall survival data demonstrated in the AZA-001 study of patients with higher-risk MDS. Azacitidine has demonstrated significant and clinically meaningful prolongation of survival in higher-risk patients with MDS and has changed the natural history of these disorders. The agent maintains a relatively safe toxicity profile, even in older patients. The role of azacitidine has been explored in the treatment of AML and chronic myelomonocytic leukemia and has also been studied in the peritransplant setting. Azacitidine has been combined with other novel agents such as lenalidomide, histone deacetylase inhibitors and growth factors in the hope of achieving improved outcomes. Currently, both intravenous and subcutaneous forms of azacitidine are approved for use in the USA with the oral form being granted fast track status by the FDA.
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