Definition and management of ruxolitinib treatment failure in myelofibrosis

Blood Cancer Journal

Volumn 4, Issue 12, 2014, Pages e268-

  Pardanani, A ^a   Tefferi, A ^a  

^a MAYO CLINIC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

5 AZA 2' DEOXYCYTIDINE; ALPHA INTERFERON; ANTIANEMIC AGENT; AZACITIDINE; CLADRIBINE; CORTICOSTEROID; DANAZOL; DAUNORUBICIN; FRESH FROZEN PLASMA; HYDROXYUREA; HYPERTENSIVE FACTOR; ISOCITRATE DEHYDROGENASE 1; ISOCITRATE DEHYDROGENASE 2; JANUS KINASE 1; JANUS KINASE 1 INHIBITOR; JANUS KINASE 2; JANUS KINASE 2 INHIBITOR; JANUS KINASE INHIBITOR; MOMELOTINIB; PACRITINIB; PROTHROMBIN COMPLEX; RECOMBINANT BLOOD CLOTTING FACTOR 7A; RUXOLITINIB; STAT PROTEIN; TRANSCRIPTION FACTOR EZH2; UNCLASSIFIED DRUG; VON WILLEBRAND FACTOR; VORICONAZOLE; PROTEIN KINASE INHIBITOR; PYRAZOLE DERIVATIVE;

ACUTE KIDNEY FAILURE; ACUTE MYELOBLASTIC LEUKEMIA; ALTERNATIVE MEDICINE; ANEMIA; ARTICLE; ARTIFICIAL EMBOLISM; ARTIFICIAL VENTILATION; BLOOD CELL COUNT; CAPILLARY LEAK SYNDROME; CARDIOGENIC SHOCK; CHRONIC MYELOMONOCYTIC LEUKEMIA; CLINICAL TRIAL (TOPIC); CLONAL EVOLUTION; CRYPTOCOCCUS NEOFORMANS; DIARRHEA; DISEASE COURSE; DISEASE PREDISPOSITION; DISSEMINATED INTRAVASCULAR CLOTTING; DIZZINESS; DOWN REGULATION; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG FATALITY; DRUG MEGADOSE; DRUG RESISTANCE; DRUG SAFETY; DRUG WITHDRAWAL; ECCHYMOSIS; ERYTHROCYTE TRANSFUSION; GRAFT VERSUS HOST REACTION; GRANULOCYTIC SARCOMA; HEADACHE; HEMATOMA; HEPATITIS B VIRUS; HERPES SIMPLEX VIRUS; HUMAN; IMMUNOSUPPRESSIVE TREATMENT; INDUCTION CHEMOTHERAPY; INTENTION TO TREAT ANALYSIS; INTERVENTIONAL RADIOLOGY; LEUKOCYTOSIS; MALIGNANT TRANSFORMATION; MILIARY TUBERCULOSIS; MYELOFIBROSIS; NEUTROPENIA; OPPORTUNISTIC INFECTION; PATIENT COMPLIANCE; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PNEUMOCYSTIS JIROVECI; QUALITY OF LIFE; RADIATION DOSE REDUCTION; RANDOMIZED CONTROLLED TRIAL (TOPIC); REMISSION; RESPIRATORY DISTRESS; RETINITIS; SHOCK; SIGNAL TRANSDUCTION; SPLEEN INFARCTION; SPLEEN SIZE; SPLENECTOMY; SPLENOMEGALY; SYMPTOM ASSESSMENT; THROMBOCYTE FUNCTION; THROMBOCYTE TRANSFUSION; THROMBOCYTOPENIA; TOXOPLASMA GONDII; TREATMENT FAILURE; TREATMENT RESPONSE; TUMOR LYSIS SYNDROME; VIRUS REACTIVATION; WITHDRAWAL SYNDROME; PRIMARY MYELOFIBROSIS;

HUMANS; PRIMARY MYELOFIBROSIS; PROTEIN KINASE INHIBITORS; PYRAZOLES; REMISSION INDUCTION;

EID: 84919422157     PISSN: None     EISSN: 20445385     Source Type: Journal    
DOI: 10.1038/bcj.2014.84     Document Type: Article

References (56)

1. James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature 2005; 434: 1144-1148.
2. Pardanani AD, Levine RL, Lasho T, Pikman Y, Mesa RA, Wadleigh M et al. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients. Blood 2006; 108: 3472-3476.
3. Pikman Y, Lee BH, Mercher T, McDowell E, Ebert BL, Gozo M et al. MPLW515L is a novel somatic activating mutation in myelofibrosis with myeloid metaplasia. PLoS Med 2006; 3: e270.
4. Tefferi A, Guglielmelli P, Larson DR, Finke C, Wassie EA, Pieri L et al. Long-term survival and blast transformation in molecularly-annotated essential thrombocythemia, polycythemia vera and myelofibrosis. Blood 2014; 124: 2507-2513.
5. Tefferi A, Lasho TL, Jimma T, Finke CM, Gangat N, Vaidya R et al. One thousand patients with primary myelofibrosis: the mayo clinic experience. Mayo Clin Proc 2012; 87: 25-33.
6. Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S et al. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol 2011; 29: 392-397.
7. Guglielmelli P, Lasho TL, Rotunno G, Score J, Mannarelli C, Pancrazzi A et al. The number of prognostically detrimental mutations and prognosis in primary myelofibrosis: an international study of 797 patients. Leukemia 2014; 28: 1804-1810.
8. Tefferi A, Guglielmelli P, Lasho TL, Rotunno G, Finke C, Mannarelli C et al. CALR and ASXL1 mutations-based molecular prognostication in primary myelofibrosis: an international study of 570 patients. Leukemia 2014; 28: 1494-1500.
9. Tefferi A, Abdel-Wahab O, Cervantes F, Crispino JD, Finazzi G, Girodon F et al. Mutations with epigenetic effects in myeloproliferative neoplasms and recent progress in treatment: Proceedings from the 5th International Post-ASH Symposium. Blood Cancer J 2011; 1: e7.
10. Tefferi A. Primary myelofibrosis: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol 2014; 89: 915-925.
11. Ballen K. How to manage the transplant question in myelofibrosis. Blood Cancer J 2012; 2: e59.
12. Verstovsek S, Kantarjian H, Mesa RA, Pardanani AD, Cortes-Franco J, Thomas DA et al. Safety and efficacy of INCB018424, a JAK1 and JAK2 inhibitor, in myelofibrosis. N Engl J Med 2010; 363: 1117-1127.
13. Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF et al. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med 2012; 366: 799-807.
14. Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V et al. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med 2012; 366: 787-798.
15. Jakafi (Ruxolitinib) label. http://www.accessdata.fda.gov/drugsatfda-docs/label/2011/ 202192lbl.pdf.
16. Cervantes F, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Sirulnik A, Stalbovskaya V 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: 4047-4053.
17. Verstovsek S, Mesa R, Gotlib J, Levy R, Gupta V, DiPersio J et al. Long-term outcomes of ruxolitinib therapy in patients with myelofibrosis: 3-year update from COMFORT-I. Blood 2013; 122, abstract 396.
18. Fonseca E, Silver RT, Kazis L, Usman Iqbal S, Rose M, Khan N et al. Ruxolitinib discontinuation in patients with myelofibrosis: an analysis from clinical practice. Blood 2013; 122, abstract 2833.
19. Tefferi A, Litzow MR, Pardanani A. Long-term outcome of treatment with ruxolitinib in myelofibrosis. N Engl J Med 2011; 365: 1455-1457.
20. Verstovsek S, Kantarjian HM, Estrov Z, Cortes JE, Thomas DA, Kadia T 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: 1202-1209.
21. Kremyanskaya M, Mascarenhas J, Rampal R, Hoffman R. Development of extramedullary sites of leukaemia during ruxolitinib therapy for myelofibrosis. Br J Haematol2014; 167: 144-146.
22. Tefferi A, Pardanani A. Serious adverse events during ruxolitinib treatment discontinuation in patients with myelofibrosis. Mayo Clin Proc2011; 86: 1188-1191.
23. Dai T, Friedman EW, Barta SK. Ruxolitinib withdrawal syndrome leading to tumor lysis. J Clin Oncol2013; 31: e430-e432.
24. Beauverd Y, Samii K. Acute respiratory distress syndrome in a patient with primary myelofibrosis after ruxolitinib treatment discontinuation. Int J Hematol2014; 100: 498-501.
25. Robin M, Francois S, Huynh A, Cassinat B, Bay J-O, Cornillon J et al. Ruxolitinib before allogeneic hematopoietic stem cell transplantation (HSCT) in patients with myelofibrosis: a preliminary descriptive report of the JAK ALLO study, a phase II trial sponsored By Goelams-FIM in collaboration With The Sfgmtc. Blood 2013; 122, abstract 306.
26. Kroger N, Alchalby H, Ditschkowski M, Wolf D, Wulf G, Zabelina T et al. Ruxolitinib as pretreatment before allogeneic stem cell transplantation for myelofibrosis. Blood 2013; 122, abstract 392.
27. Lebon D, Rubio M, Legrand F, Kiladjian J-J, Mohty M, Cahn J-Y et al. Ruxolitinib for patients with primary or secondary myelofibrosis before allogeneic hematopoietic stem cell transplantation (allo-HSCT): a retrospective study of the Société Française De Greffe De Moelle Et De Thérapie Cellulaire (SFGM-TC). Blood 2013; 122, abstract 2111.
28. Barosi G, Zhang MJ, Peter Gale R. Does ruxolitinib improve survival of persons with MPN-associated myelofibrosis? Should it? Leukemia 2014; 28: 2267-2270.
29. Gale RP, Barosi G. Commentary. Leukemia Res2014; 38: 1013-1015.
30. Harrison C, Schaap N, Zweegman S, Jourdan E, Kiladjian J, Cervantes F et al. Efficacy and safety of Fedratinib (SAR302503/TG101348) in patients with intermediate- or high-risk myelofibrosis (MF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF previously treated with Ruxolitinib: interim results from a phase II tudy (JAKARTA-2). Blood 2013; 122: abstract 661.
31. Santos FP, Tam CS, Kantarjian H, Cortes J, Thomas D, Pollock R et al. Splenectomy in patients with myeloproliferative neoplasms: efficacy, complications and impact on survival and transformation. Leuk Lymphoma 2014; 55: 121-127.
32. Mesa RA, Nagorney DS, Schwager S, Allred J, Tefferi A. Palliative goals, patient selection, and perioperative platelet management: outcomes and lessons from 3 decades of splenectomy for myelofibrosis with myeloid metaplasia at the Mayo Clinic. Cancer 2006; 107: 361-370.
33. Tefferi A, Mesa RA, Nagorney DM, Schroeder G, Silverstein MN. Splenectomy in myelofibrosis with myeloid metaplasia: a single-institution experience with 223 patients. Blood 2000; 95: 2226-2233.
34. Cervantes F. How I treat splenomegaly in myelofibrosis. Blood Cancer J 2011; 1: e37.
35. McMullin MF, Harrison C, Niederwieser D, Demuynck H, Jakel N, Sirulnik A et al. The use of erythropoietic-stimulating agents (ESAs) with ruxolitinib in patients with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (PPV-MF), and post-essential thrombocythemia myelofibrosis (PET-MF). Blood 2012; 120, abstract 2838.
36. Grunwald MR, Spivak JL. Ruxolitinib enhances platelet production in patients with thrombocytopenic myelofibrosis. J Clin Oncol 2014; e-pub ahead of print 23 June 2014; doi:10.1200/JCO.2013.51.0057.
37. Pardanani A, Brown P, Neben-Wittich M, Tobin R, Tefferi A. Effective management of accelerated phase myelofibrosis with low-dose splenic radiotherapy. Am J Hematol 2010; 85: 715-716.
38. Quintas-Cardama A, Tong W, Kantarjian H, Thomas D, Ravandi F, Kornblau S et al. A phase II study of 5-azacitidine for patients with primary and post-essential thrombocythemia/polycythemia vera myelofibrosis. Leukemia 2008; 22: 965-970.
39. Liu Y, Tabarroki A, Billings S, Visconte V, Rogers HJ, Hasrouni E et al. Successful use of very low dose subcutaneous decitabine to treat high-risk myelofibrosis with Sweet syndrome that was refractory to 5-azacitidine. Leuk Lymphoma 2014; 55: 447-449.
40. Danilov AV, Relias V, Feeney DM, Miller KB. Decitabine is an effective treatment of idiopathic myelofibrosis. Br J Haematol2009; 145: 131-132.
41. Mesa RA, Verstovsek S, Rivera C, Pardanani A, Hussein K, Lasho T et al. 5-Azacitidine has limited therapeutic activity in myelofibrosis. Leukemia 2009; 23: 180-182.
42. Odenike O, Godwin J, Van Besien K, Huo D, Sher D, Burke P et al. Phase II trial of low dose, subcutaneous decitabine in myelofibrosis. Blood 2008; 112, abstract 2809.
43. Heine A, Held SA, Daecke SN, Wallner S, Yajnanarayana SP, Kurts C et al. The JAK-inhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo. Blood 2013; 122: 1192-1202.
44. Heine A, Brossart P, Wolf D. Ruxolitinib is a potent immunosuppressive compound: is it time for anti-infective prophylaxis? Blood 2013; 122: 3843-3844.
45. Wysham NG, Sullivan DR, Allada G. An opportunistic infection associated with ruxolitinib, a novel janus kinase 1,2 inhibitor. Chest 2013; 143: 1478-1479.
46. Lee SC, Feenstra J, Georghiou PR. Pneumocystis jiroveci pneumonitis complicating ruxolitinib therapy. BMJ Case Rep 2014; e-pub ahead of print 2 June 2014; doi:10.1136/bcr-2014-204950.
47. Goldberg RA, Reichel E, Oshry LJ. Bilateral toxoplasmosis retinitis associated with ruxolitinib. N Engl J Med2013; 369: 681-683.
48. Colomba C, Rubino R, Siracusa L, Lalicata F, Trizzino M, Titone L et al. Disseminated tuberculosis in a patient treated with a JAK2 selective inhibitor: a case report. BMC Res Notes 2012; 5: 552.
49. Caocci G, Murgia F, Podda L, Solinas A, Atzeni S, La Nasa G et al. Reactivation of hepatitis B virus infection following ruxolitinib treatment in a patient with myelofibrosis. Leukemia 2014; 28: 225-227.
50. Tong LX, Jackson J, Kerstetter J, Worswick SD. Reactivation of herpes simplex virus infection in a patient undergoing ruxolitinib treatment. J Am Acad Dermatol 2014; 70: e59-e60.
51. Wathes R, Moule S, Milojkovic D. Progressive multifocal leukoencephalopathy associated with ruxolitinib. N Engl J Med2013; 369: 197-198.
52. Tefferi A, Pardanani A, Gangat N, Begna KH, Hanson CA, Van Dyke DL et al. Leukemia risk models in primary myelofibrosis: an International Working Group study. Leukemia 2012; 26: 1439-1441.
53. Tefferi A, Jimma T, Gangat N, Vaidya R, Begna KH, Hanson CA et al. Predictors of greater than 80% 2-year mortality in primary myelofibrosis: a Mayo Clinic study of 884 karyotypically annotated patients. Blood 2011; 118: 4595-4598.
54. Eghtedar A, Verstovsek S, Estrov Z, Burger J, Cortes J, Bivins C et al. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia. Blood 2012; 119: 4614-4618.
55. Tefferi A, Cervantes F, Mesa R, Passamonti F, Verstovsek S, Vannucchi AM et al. Revised response criteria for myelofibrosis: International Working Group- Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood 2013; 122: 1395-1398.
56. Barosi G, Tefferi A, Besses C, Birgegard G, Cervantes F, Finazzi G et al. Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements froim European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT). Leukemia 2014; e-pub ahead of print 25 August 2014; doi:10.1038/leu.2014.250.