Results of COMFORT-I, a randomized double-blind phase III trial of JAK 1/2 inhibitor INCB18424 (424) versus placebo (PB) for patients with myelofibrosis (MF).

Verstovsek, S.; Mesa, Ruben A.; Gotlib, Jason; Levy, RichardL.; Gupta, Vipul; DiPersio, John F.; Catalano, John; Deininger, M.; Miller, Carole B.; Silver, Richard T.; Talpaz, Moshe; Winton, Elliott F.; Harvey, John Collins; Vaddi, Kris; Erickson‐Viitanen, Susan; Koumenis, Iphigenia L.; Sun, Wenjing; Sandor, Victor; Kantarjian, H.

doi:10.1200/jco.2011.29.15_suppl.6500

Cited by 36 publications

(42 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Recently developed medical therapies, including Janus kinase 2 (JAK2) inhibitors, have been successful at reducing cytokine burden, symptom burden, and overall fatigue. 29 Due to these therapeutic advances and the high burden of fatigue, the European LeukemiaNet and International Working Group-Myeloproliferative Neoplasms Research and Treatment has incorporated the assessment of symptom burden into the determination of therapy response. 30 Similarly, we recommend that patients with a severe fatigue burden also be screened for medical and psychological comorbidities that may contribute to fatigue in both clinical and research settings.…”

Section: Discussionmentioning

confidence: 99%

Comprehensively understanding fatigue in patients with myeloproliferative neoplasms

Scherber

Kosiorek

Senyak

et al. 2015

Cancer

View full text Add to dashboard Cite

BACKGROUND Patients with myeloproliferative neoplasms (MPNs) experience a high persistence, prevalence, and severity of fatigue. There is currently only limited information regarding factors that contribute to fatigue in patients with MPNs. METHODS A 70‐item, Internet‐based survey regarding fatigue was developed by MPN investigators and patients/advocates and hosted by the Mayo Clinic Survey Research Center. RESULTS Fatigue was found to be prevalent and severe among international survey respondents (1788 respondents). Higher body mass index (P<.001), current use of alcohol (P<.001), and current tobacco use (P = .0025) were found to be significantly associated with greater fatigue. Moderate/severe fatigue was present more frequently in those individuals who did not exercise compared with those who reported exercising at least once per week (P<.001). Medical comorbidities found to be significantly associated with greater fatigue included restless leg syndrome (P = .006), diabetes mellitus (P = .045), fibromyalgia (P < 0.001), chronic fatigue syndrome (P = .006), and chronic kidney disease (P = .02). Current use of antidepressants (P<.001), antihistamines (P = .0276), antianxiety medications (P = .0357), and prescription pain medications (P<.001) were found to be associated with worsened fatigue. Nearly 25% of respondents scored > 2 on the Patient Health Questionnaire, indicating a high probability of depression. Higher Brief Fatigue Inventory score, Myeloproliferative Neoplasm Total Symptom Score, and individual symptom items were all associated with a higher likelihood of depressive symptoms (P<.0001). CONCLUSIONS The management of fatigue should be multifactorial, with a comprehensive assessment and treatment plan to address all modifiable fatigue etiologies. Patients with MPNs likely have a higher prevalence of mood disturbances compared with the general population, suggesting the need to assess and intervene in this domain. Cancer 2016;122:477–485. © 2015 American Cancer Society.

show abstract

Section: Discussionmentioning

confidence: 99%

Comprehensively understanding fatigue in patients with myeloproliferative neoplasms

Scherber

Kosiorek

Senyak

et al. 2015

Cancer

View full text Add to dashboard Cite

show abstract

“…71 After a median follow-up of 32.2 weeks, 41.9% of patients on ruxolitinib (vs 0.7% on placebo) achieved spleen response. Median duration of spleen response was not reached at that point.…”

Section: Phase 3 Studiesmentioning

confidence: 99%

JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths

Tefferi

2012

Blood

160

137

View full text Add to dashboard Cite

“…The first study, COMFORT-I, assessed the activity of ruxolitinib at 15 or 20 mg twice daily (depending on the baseline platelet level) against placebo in 309 patients. 54 The second, COMFORT-II, compared the activity of ruxolitininb against "best-available therapy" in 219 patients randomized 2:1 to the active arm. 34 The primary study end point of Ն 35% spleen volume reduction from baseline as measured by magnetic resonance imaging or computed tomography scan, at 24 (COMFORT-I) or 48 (COMFORT-II) weeks was reached by 41.9% and 28.5% of the patients, respectively, compared with 0.7% and 0% in the control arms (P Ͻ .0001).…”

Section: Jak2 Inhibitorsmentioning

confidence: 99%

Management of Myelofibrosis

Vannucchi

2011

Hematology

View full text Add to dashboard Cite

Myelofibrosis (MF), either primary or arising from previous polycythemia vera (PV) or essential thrombocythemia (ET), is the worst among the chronic myeloproliferative neoplasms in terms of survival and quality of life. Patients with MF have to face several clinical issues that, because of the poor effectiveness of medical therapy, surgery or radiotherapy, represent largely unmet clinical needs. Powerful risk stratification systems, applicable either at diagnosis using the International Prognostic Scoring System (IPSS) or during the variable course of illness using the Dynamic International Prognostic Scoring System (DIPSS) and DIPSS Plus, allow recognition of categories of patients with survival times ranging from decades to Ͻ 2 years. These scores are especially important for therapeutic decisions that include allogeneic stem cell transplantation (allogeneic SCT), the only curative approach that still carries a nonnegligible risk of morbidity and mortality even with newest reduced intensity conditioning (RIC) regimens. Discovery of JAK2V617F mutation prompted the development of clinical trials using JAK2 inhibitors; these agents overall have resulted in meaningful symptomatic improvement and reduction of splenomegaly that were otherwise not achievable with conventional therapy. Intriguing differences in the efficacy and tolerability of JAK2 inhibitors are being recognized, which could lead to a nonoverlapping spectrum of activity/safety. Other agents that do not directly target JAK2 and have shown symptomatic efficacy in MF are represented by inhibitors of the mammalian target of rapamycin (mTOR) and histone deacetylases (HDACs). Pomalidomide appears to be particularly active against MF-associated anemia. However, because these agents are all poorly effective in reducing the burden of mutated cells, further advancements are needed to move from enhancing our ability to palliate the disease to arriving at an actual cure for MF.

show abstract

Results of COMFORT-I, a randomized double-blind phase III trial of JAK 1/2 inhibitor INCB18424 (424) versus placebo (PB) for patients with myelofibrosis (MF).

Cited by 36 publications

References 0 publications

Comprehensively understanding fatigue in patients with myeloproliferative neoplasms

Comprehensively understanding fatigue in patients with myeloproliferative neoplasms

JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths

Management of Myelofibrosis

Contact Info

Product

Resources

About