Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: Results of a median 3-year follow-up of COMFORT-I

Haematologica

Volumn 100, Issue 4, 2015, Pages 479-488

  Verstovsek, Srdan ^a   Mesa, Ruben A ^b   Gotlib, Jason ^c   Levy, Richard S ^d   Gupta, Vikas ^e   Dipersio, John F ^f   Catalano, John V ^g   Deininger, Michael W N ^h   Miller, Carole B ⁱ   Silver, Richard T ^j   Talpaz, Moshe ^k   Winton, Elliott F ^l   Harvey, Jimmie H ^m   Arcasoy, Murat O ⁿ   Hexner, Elizabeth O ^o   Lyons, Roger M ^p   Raza, Azra ^q   Vaddi, Kris ^d   Sun, William ^d   Peng, Wei ^d   Sandor, Victor ^d   Kantarjian, Hagop ^a   more..

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b MAYO CLINIC   (United States)

^c STANFORD CANCER INSTITUTE   (United States)

^d Drug Metabolism Pharmacokinetics Clinical Pharmacology   (United States)

^e UNIVERSITY OF TORONTO   (Canada)

^f WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g MONASH UNIVERSITY   (Australia)

^h OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

ⁱ St Agnes Cancer Institute   (United States)

^j WEILL CORNELL MEDICAL CENTER   (United States)

^k UNIVERSITY OF MICHIGAN   (United States)

^l EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^m Birmingham Hematology and Oncology   (United States)

ⁿ DUKE UNIVERSITY HEALTH SYSTEM   (United States)

^o UNIVERSITY OF PENNSYLVANIA   (United States)

^p Developmental Therapeutics Committee and Co Chair of the Genitourinary Committee   (United States)

^q Department of Orthopaedic Surgery   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

JANUS KINASE 2; PLACEBO; RUXOLITINIB; JANUS KINASE; PROTEIN KINASE INHIBITOR; PYRAZOLE DERIVATIVE;

ABDOMINAL PAIN; ACUTE GRANULOCYTIC LEUKEMIA; ANEMIA; ARTHRALGIA; ARTICLE; CONSTIPATION; COUGHING; DIARRHEA; DISEASE COURSE; DRUG EFFICACY; DRUG EXPOSURE; DRUG SAFETY; DYSPNEA; ECCHYMOSIS; FATIGUE; FEVER; HEADACHE; HUMAN; INSOMNIA; MAJOR CLINICAL STUDY; MYELOFIBROSIS; NAUSEA AND VOMITING; OVERALL SURVIVAL; PAIN; PERIPHERAL EDEMA; PHASE 3 CLINICAL TRIAL (TOPIC); QUALITY OF LIFE; QUESTIONNAIRE; RANDOMIZED CONTROLLED TRIAL (TOPIC); SPLEEN SIZE; SPLENOMEGALY; THROMBOCYTE COUNT; THROMBOCYTOPENIA; UPPER RESPIRATORY TRACT INFECTION; URINARY TRACT INFECTION; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; FOLLOW UP; MORTALITY; ORGAN SIZE; PATHOLOGY; PRIMARY MYELOFIBROSIS; SPLEEN; TREATMENT OUTCOME;

FOLLOW-UP STUDIES; HUMANS; JANUS KINASES; ORGAN SIZE; PRIMARY MYELOFIBROSIS; PROTEIN KINASE INHIBITORS; PYRAZOLES; QUALITY OF LIFE; RANDOMIZED CONTROLLED TRIALS AS TOPIC; SPLEEN; TREATMENT OUTCOME;

EID: 84926337489     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2014.115840     Document Type: Article

References (35)

1. Abdel-Wahab O, Levine RL. Primary myelofibrosis: update on definition, pathogenesis, and treatment. Annu Rev Med. 2009;60:233-245.
2. Mesa RA, Schwager S, Radia D, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res. 2009;33(9):1199-1203.
3. Tefferi A. Myelofibrosis with myeloid metaplasia. N Engl J Med. 2000;342(17):1255-1265.
4. Gupta V, Hari P, Hoffman R. Allogeneic hematopoietic cell transplantation for myelofibrosis in the era of JAK inhibitors. Blood. 2012;120(7):1367-1379.
5. James C, Ugo V, Le Couedic JP, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144-1148.
6. Kralovics R, Passamonti F, Buser AS, et al. A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med. 2005;352(17):1779-1790.
7. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054-1061.
8. Levine RL, Wadleigh M, Cools J, et al. Activating mutation in the tyrosine kinase JAK2 in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis. Cancer Cell. 2005;7(4):387-397.
9. Tefferi A, Vainchenker W. Myelo-proliferative neoplasms: molecular pathophysiology, essential clinical understanding, and treatment strategies. J Clin Oncol. 2011;29(5):573-582.
10. Pikman Y, Lee BH, Mercher T, et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med. 2006;3(7):e270.
11. Rumi E, Pietra D, Guglielmelli P, et al. Acquired copy-neutral loss of heterozygosity of chromosome 1p as a molecular event associated with marrow fibrosis in MPLmutated myeloproliferative neoplasms. Blood. 2013;121(21):4388-4395.
12. Rampal R, Al-Shahrour F, Abdel-Wahab O, et al. Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis. Blood. 2014;123(22):e123-133.
13. Vainchenker W, Delhommeau F, Constantinescu SN, Bernard OA. New mutations and pathogenesis of myeloproliferative neoplasms. Blood. 2011;118(7):1723-1735.
14. Klampfl T, Gisslinger H, Harutyunyan AS, et al. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013;369(25):2379-2390.
15. Nangalia J, Massie CE, Baxter EJ, et al. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2. N Engl J Med. 2013;369(25):2391-2405.
16. Passamonti F, Maffioli M, Caramazza D, Cazzola M. Myeloproliferative neoplasms: from JAK2 mutations discovery to JAK2 inhibitor therapies. Oncotarget. 2011;2(6): 485-490.
17. Rampal R, Al-Shahrour F, Abdel-Wahab O, et al. Integrated genomic analysis illustrates the central role of JAK-STAT pathway activation in myeloproliferative neoplasm pathogenesis. Blood. 2014;123(22):e123-e133.
18. Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113(13):2895-2901.
19. Verstovsek S, Mesa RA, Gotlib J, et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012;366(9):799-807.
20. Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012;366(9):787-798.
21. Mesa RA, Gotlib J, Gupta V, et al. Effect of ruxolitinib therapy on myelofibrosis-related symptoms and other patient-reported outcomes in COMFORT-I: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2013;31(10):1285-1292.
22. Cervantes F, Kiladjian J-J, Niederwieser D, et al. Long-term efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for the treatment of myelofibrosis. Blood. 2012;120(21):abstract 801.
23. Cervantes F, Vannucchi AM, Kiladjian JJ, et al. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013;122(25):4047-4053.
24. Verstovsek S, Gotlib J, Gupta V, et al. Management of cytopenias in patients with myelofibrosis treated with ruxolitinib and effect of dose modifications on efficacy outcomes. OncoTarget Ther. 2014;4(7):13-21.
25. Robins JM, Tsiatis A. Correcting for noncompliance in randomized trials using rank preserving structural failure time models. Commun Stat Theory Methods. 1991;20(8): 2609-2631.
26. Demetri GD, Garrett CR, Schoffski P, et al. Complete longitudinal analyses of the randomized, placebo-controlled, phase III trial of sunitinib in patients with gastrointestinal stromal tumor following imatinib failure. Clin Cancer Res. 2012;18(11):3170-3179.
27. Sternberg CN, Hawkins RE, Wagstaff J, et al. A randomised, double-blind phase III study of pazopanib in patients with advanced and/or metastatic renal cell carcinoma: final overall survival results and safety update. Eur J Cancer. 2013;49(6):1287-1296.
28. Lawless JF. Statistical Models and Methods for Lifetime Data. Hoboken, NJ: Wiley-Interscience; 2002.
29. Yavari P, Abadi A, Amanpour F, Bajdik C. Applying conventional and saturated generalized gamma distributions in parametric survival analysis of breast cancer. Asian Pac J Cancer Prev. 2012;13(5):1829-1831.
30. Tefferi A, Cervantes F, Mesa R, et al. Revised response criteria for myelofibrosis: International Working Group-Myelo-proliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013;122(8):1395-1398.
31. Incyte Corporation. Jakafi (ruxolitinib) tablets [prescribing information]. Wilmington, DE: Incyte Corporation; 2014.
32. Hamidou Z, Dabakuyo TS, Bonnetain F. Impact of response shift on longitudinal quality-of-life assessment in cancer clinical trials. Expert Rev Pharmacoecon Outcomes Res. 2011;11(5):549-559.
33. Vannucchi AM, Kantarjian H, Kiladjian JJ, et al. A pooled overall survival analysis of the COMFORT studies: 2 randomized phase 3 trials of ruxolitinib for the treatment of myelofibrosis. Presented at: 55th ASH Annual Meeting and Exposition; December 8, 2013; New Orleans, LA; (abstract 2820).
34. Verstovsek S, Mesa AR, Gotlib J, et al. Longterm outcomes of ruxolitinib therapy in patients with myelofibrosis: 3-year update from COMFORT-I. Blood. 2013;122(21): abstract 396.
35. Verstovsek S, Kantarjian HM, Estrov Z, et al. Long-term outcomes of 107 patients with myelofibrosis receiving JAK1/JAK2 inhibitor ruxolitinib: survival advantage in comparison to matched historical controls. Blood. 2012;120(6):1202-1209.