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Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies

Annals of Hematology volume 97, pages 617–627 (2018)Cite this article

Abstract

Ruxolitinib was well tolerated and superior to best available therapy (including interferon [IFN]) in controlling hematocrit without phlebotomy eligibility, normalizing blood counts, and improving polycythemia vera-related symptoms in the Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care (RESPONSE) studies. This ad hoc analysis focuses on ruxolitinib in relation to IFN in the RESPONSE studies, with attention on the following: (1) safety and efficacy of ruxolitinib and best available therapy in patients who received IFN before study randomization, (2) safety and efficacy of IFN during randomized treatment in best available therapy arm, and (3) use of ruxolitinib after crossover from best available therapy in IFN-treated patients. IFN exposure before randomization had little effect on the efficacy or safety of ruxolitinib. In the randomized treatment arms, ruxolitinib was superior to IFN in efficacy [hematocrit control (RESPONSE = 60% of ruxolitinib vs 23% of IFN patients; RESPONSE-2 = 62% of ruxolitinib vs 15% of IFN patients)] and was tolerated better in hydroxyurea-resistant or hydroxyurea-intolerant patients. After crossing over to receive ruxolitinib, patients who had initially received IFN and did not respond had improved hematologic and spleen responses (62% of patients at any time after crossover) and an overall reduction in phlebotomy procedures. Rates and incidences of the most common adverse events decreased after crossover to ruxolitinib, except for infections (primarily grade 1 or 2). These data suggest that ruxolitinib is efficacious and well tolerated in patients who were previously treated with IFN. The RESPONSE (NCT01243944) and RESPONSE-2 (NCT02038036) studies were registered at clinicaltrials.gov.

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Acknowledgments

We thank Archana Rai and Ambrin Fatima, PhD, from Novartis Healthcare Pvt. Ltd., for their medical writing assistance with this manuscript.

Author information

Affiliations

  1. Centre d’Investigations Cliniques (CIC1427), Hôpital Saint-Louis, AP-HP, INSERM, CLIP2 “Saint-Louis - Paris Nord,” Early Phase Research Center, Université Paris Diderot, 1, Avenue Claude Vellefaux, 75010, Paris, France

    Jean-Jacques Kiladjian

  2. CRIMM, Center for Research and Innovation of Myeloproliferative Neoplasms, AOU Careggi, Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

    Paola Guglielmelli

  3. Johannes Wesling Academic Medical Center, University of Hannover Teaching Hospital, Minden, Germany

    Martin Griesshammer

  4. Department of Hematology, Ege University Medical Faculty, Izmir, Turkey

    Guray Saydam

  5. St. István and St. László Hospital, Semmelweis University, Budapest, Hungary

    Tamas Masszi

  6. Royal Brisbane Hospital, Herston, Australia

    Simon Durrant

  7. Department of Hematology, University of Insubria, Varese, Italy

    Francesco Passamonti

  8. Incyte Corporation, Wilmington, DE, USA

    Mark Jones & Huiling Zhen

  9. Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA

    Jingjin Li, Brian Gadbaw & Mahmudul Khan

  10. Novartis AG, Basel, Switzerland

    Julian Perez Ronco

  11. The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Srdan Verstovsek

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  1. Jean-Jacques Kiladjian
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  2. Paola Guglielmelli
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  9. Huiling Zhen
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  14. Srdan Verstovsek
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Correspondence to Jean-Jacques Kiladjian.

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Conflict of interest

JJK reports grants and personal fees from Novartis, grants and personal fees from AOP Orphan, during the conduct of the study; personal fees from Shire, outside the submitted work. PG has nothing to disclose. MG participated in speaker bureau and advisory boards for Novartis, Shire, and AOP Orphan, outside the submitted work. GS received research funding from Novartis, participated in speaker bureau for Novartis, and received honoraria from Novartis, Celgene, Bristol-Myers Squibb, and Gilead, outside the submitted work. TM served as a consultant for Takeda, Novartis, Bristol-Myers Squibb, and Janssen Cilag, outside the submitted work. SD has nothing to disclose. FP participated in speaker bureau and advisory board for Novartis. MJ and HZ are employees of Incyte Corporation and own stocks of company. JL, BG, JPR, and MK are employees of Novartis. JL, MK and BG own stocks of company. SV participated in advisory boards for Novartis and Incyte.

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This study was approved by the institutional review board (IRB). Each investigator site IRB approved the respective protocols. Informed consent was obtained from all patients for being included in the study.

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Kiladjian, JJ., Guglielmelli, P., Griesshammer, M. et al. Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies. Ann Hematol 97, 617–627 (2018). https://doi.org/10.1007/s00277-017-3225-1

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  • DOI: https://doi.org/10.1007/s00277-017-3225-1

Keywords

  • Chronic myeloproliferative neoplasms
  • Polycythemia vera
  • Ruxolitinib
  • Interferon