Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: Results of a median 3-year follow-up of COMFORT-I
Srdan Verstovsek,Ruben A. Mesa,Jason Gotlib,Richard S. Levy,Vikas Gupta,John F. DiPersio,John Catalano,Michael W. Deininger,Carole B. Miller,Richard T. Silver,Moshe Talpaz,Elliott F. Winton,Jimmie H. Harvey,Murat O. Arcasoy,Elizabeth O. Hexner,Roger M. Lyons,Ronald Paquette,Azra Raza,Kris Vaddi,Susan Erickson-Viitanen,William Sun,Victor Sandor,Hagop M. Kantarjian +22 more
TLDR
Longer-term data continue to support the efficacy and safety of ruxolitinib in patients with myelofibrosis, and exploratory analyses suggest that crossover may have contributed to an underestimation of the true survival difference between the treatment groups.Abstract:
In the phase III COMFORT-I study, the Janus kinase 1 (JAK1)/JAK2 inhibitor ruxolitinib provided significant improvements in splenomegaly, key symptoms, and quality-of-life measures and was associated with an overall survival benefit relative to placebo in patients with intermediate-2 or high-risk myelofibrosis. This planned analysis assessed the long-term efficacy and safety of ruxolitinib at a median follow-up of 149 weeks. At data cutoff, approximately 50% of patients originally randomized to ruxolitinib remained on treatment whereas all patients originally assigned to placebo had discontinued or crossed over to ruxolitinib. At week 144, mean spleen volume reduction was 34% with ruxolitinib. Previously observed improvements in quality-of-life measures were sustained with longer-term ruxolitinib therapy. Overall survival continued to favor ruxolitinib despite the majority of placebo patients crossing over to ruxolitinib [hazard ratio 0.69 (95% confidence interval: 0.46–1.03); P=0.067]. Exploratory analyses suggest that crossover may have contributed to an underestimation of the true survival difference between the treatment groups. Ruxolitinib continued to be generally well tolerated; there was no pattern of worsening grade ≥3 anemia or thrombocytopenia with longer-term ruxolitinib exposure. These longer-term data continue to support the efficacy and safety of ruxolitinib in patients with myelofibrosis. The study is registered at clinicaltrials.gov: NCT00952289.read more
Citations
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Kinase-targeted cancer therapies: progress, challenges and future directions
Khushwant S. Bhullar,Naiara Orrego Lagarón,Eileen M. McGowan,Indu Parmar,Amitabh Jha,Basil P. Hubbard,H.P. Vasantha Rupasinghe +6 more
TL;DR: The human genome encodes 538 protein kinases that transfer a γ-phosphate group from ATP to serine, threonine, or tyrosine residues, which are the second most targeted group of drug targets, after the G-protein-coupled receptors.
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Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis
Claire N. Harrison,Alessandro M. Vannucchi,Jean-Jacques Kiladjian,Haifa Kathrin Al-Ali,Heinz Gisslinger,Laurent Knoops,Francisco Cervantes,Mark M. Jones,Kang Sun,Mari McQuitty,Viktoriya Stalbovskaya,Prashanth Gopalakrishna,T Barbui +12 more
TL;DR: It was shown that spleen volume reductions with ruxolitinib were maintained with continued therapy and may be associated with survival benefits and there was no unexpected increased incidence of adverse events with longer exposure.
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Safety and Efficacy of Fedratinib in Patients With Primary or Secondary Myelofibrosis: A Randomized Clinical Trial.
Animesh Pardanani,Claire N. Harrison,Jorge E. Cortes,Francisco Cervantes,Ruben A. Mesa,Donald Milligan,Tamas Masszi,Elena Mishchenko,Eric Jourdan,Alessandro M. Vannucchi,Mark Drummond,Mindaugas Jurgutis,Kazimierz Kuliczkowski,Emanuil Gheorghita,Francesco Passamonti,Frank Neumann,Abhay Patki,Guozhi Gao,Ayalew Tefferi +18 more
TL;DR: Fedratinib therapy significantly reduced splenomegaly and symptom burden in patients with MF and was accompanied by toxic effects in some patients, the most important being encephalopathy of unknown mechanism.
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JAK inhibitors in dermatology: The promise of a new drug class
William Damsky,Brett A. King +1 more
TL;DR: Evidence suggests that JAK inhibition might be broadly useful in dermatology, with early reports of efficacy in several other conditions, and JAK inhibitors can be administered orally or used topically and represent a promising new class of medications.
Journal ArticleDOI
Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial.
Srdan Verstovsek,Ruben A. Mesa,Jason Gotlib,Vikas Gupta,John F. DiPersio,John Catalano,Michael W. Deininger,Carole B. Miller,Richard T. Silver,Moshe Talpaz,Elliott F. Winton,Jimmie H. Harvey,Murat O. Arcasoy,Elizabeth O. Hexner,Roger M. Lyons,Ronald Paquette,Azra Raza,Mark M. Jones,Deanna Kornacki,Kang Sun,Hagop M. Kantarjian +20 more
TL;DR: The final COMFORT-I results continue to support ruxolitinib as an effective treatment for patients with intermediate-2/high-risk MF and safety profile remained consistent with previous analyses.
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