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Pegylated recombinant interferon alpha-2b vs recombinant interferon alpha-2b for the initial treatment of chronic-phase chronic myelogenous leukemia: a phase III study

Leukemia volume 18, pages 309–315 (2004)Cite this article

Abstract

Recombinant interferon alpha-2b (rIFN-α2b) is an effective therapy for chronic-phase chronic myelogenous leukemia (CML). Polyethylene glycol-modified rIFN-α2b is a novel formulation with a serum half-life (∼40 h) compatible with once-weekly dosing. This open-label, noninferiority trial randomized 344 newly diagnosed CML patients: 171 received subcutaneous pegylated rIFN-α2b (6 μg/kg/week); 173 received rIFN-α2b (5 million International Units/m2/day). Primary efficacy end point was the 12-month major cytogenetic response (MCR) rate (<35% Philadelphia chromosome-positive cells). Modified efficacy analysis included all MCRs >12 months, except for patients discontinuing treatment after 6 months and achieving an MCR on other salvage therapy. The MCR rates were 23% for pegylated rIFN-α2b vs 28% for rIFN-α2b in the primary efficacy analysis and 26 vs 28% in the prospectively modified efficacy analysis. However, a significant imbalance in baseline hematocrit (HCT), a significant predictor of cytogenetic response (P=0.0001), was discovered: 51 (30%) patients treated with pegylated rIFN-α2b had low HCT (<33%) vs 33 (19%) rIFN-α2b-treated patients. Among patients with HCT >33%, the MCR rate was 33 vs 31%. The adverse event profile of weekly pegylated rIFN-α2b was comparable to daily rIFN-α2b. Once-weekly pegylated rIFN-α2b is an active agent for the treatment of newly diagnosed CML with an efficacy and safety profile similar to daily rIFN-α2b, although statistical noninferiority was not demonstrated.

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Author notes

  1. M Michallet, F Maloisel, M Delain, A Hellmann, A Rosas, R T Silver and C Tendler: See appendix for participating investigators

Authors and Affiliations

  1. Hôpital Edouard Herriot, Lyon, France

    M Michallet

  2. Hôpital Hautepierre, Strasbourg, France

    F Maloisel

  3. Hôpital Bretonneau, Tours, France

    M Delain

  4. Medical University of Gdansk, Gdansk, Poland

    A Hellmann

  5. Centro Mexico Nacional La Raza Instituto Mexicano del Seguro Social, Mexico City, Mexico

    A Rosas

  6. New York Presbyterian Hospital-Weill Cornell Medical Center, New York, NY, USA

    R T Silver

  7. Schering-Plough, Kenilworth, NJ, USA

    C Tendler

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  1. M Michallet
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  2. F Maloisel
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  3. M Delain
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  4. A Hellmann
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  5. A Rosas
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  6. R T Silver
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  7. C Tendler
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Consortia

for the PEG-Intron CML Study Group

Corresponding author

Correspondence to M Michallet.

Appendix

Appendix

Listing of PEG-Intron CML Study Group including Schering-Plough Research Institute: Esther Rose and Helen Yeardley; Argentina: Gustavo Kusminsky; Austria: Marianne Bernhart, Gunther Gastl; Australia: Anthony Dodds, R Lindeman; Belgium: Marc Boogaerts, Louise Debusscher, Andre Efira, Micheéle Rauis; Canada: Robert Belanger, Janis Bormanis, Guy Cantin, Donna Forrest, Michael Kovacs, Pierre Laneuville, Jeffrey H Lipton, Pedro Lopez, Robert Turner; Chile: Alejandro Majlis; Columbia: Rodolfo Gomez; Denmark: Hans Karle; Finland: Tuomo Honkanen, Kalevi Oksanen; France: Frederic Bauduer, Agnes Buzyn-Veil, Sylvie Castaigne, Martine Delain, Bernard Desablens, Alain Devidas, Francois Guilhot, Denis Guyotat, Frederick Maloisel, Mauricette Michallet, Joseph Reiffers, Jean-Franccois Rossi, Philippe Rousselot, Philippe Solal-Celigny, Jean-Jaques Sotto, Michel Tulliez; Germany: Walter E Aulitzky, Olaf Brudler, Gerhard Ehninger, Ruediger Hehlmann, Christoph Huber, Christian Peschel, Peter Von Wussow; Greece: Nikolaos Anagnostopoulos, Maria Bakiris; Guatemala: Cesar Vettorazzi; Italy: Sergio Amadori, Achille Ambrosetti, Michele Baccarani, Carlo Bernasconi, Giovanna Rege Cambrin, Antonio Capaldi, Gianluigi Castoldi, Pietro Citarrella, Anna D'Emilio, Rosario Giustolisi, Luigi Gugliotta, Pietro Leoni, Anna Marina Liberati, Vincenzo Liso, Patrizio Mazza, Enrica Morra, Gianantonio Rosti, Bruno Rotoli, Ettore Volpe, Alfonso Zaccaria; Mexico: Jose Gonzalez-Llaven; Sweden: Magnus Bjorkholm, Olle Linder, Per Ljungman, Claes Malm, Stig Rodjer, Bengt Simonsson; The Netherlands: Gerrit Johan Ossenkoppele; Norway: Anders Waage; Poland: Anna Dmoszynska, Maria Podolak-Dawidziak, Tadeusz Robak, Aleksander Skotnicki; Portugal: Jorge Coutinho, Ines Nolasco, Gabriel Tamagnini; South Africa: Lydia Fourie, FC Slabber, N Novitsky; Spain: Consuelo Canizo, Francisco Cervantes, Juan Luis Steegmann; United Kingdom: Naim Akhtar, Saad Adar Al-Ishmail, David Bareford, Helen Frances Barker, D Chan, James Chang, Dominic John Culligan, JG Erskine, C Hatton, P Hillmen, R Kaczmarski, SJ Kelly, PR Kelsey, JA Lui Yin, DW Milligan, AC Newlands, A Pagliuca, H Parry, M Potter, S Rassam, Sarah Willoughby, B Woodcock; Uruguay: Martha Nese; United States of America: David Bodensteiner, Timothy Brotherton, Delvyn C Case, Gary Cohen, Laurence Elias, Stephanie Elkins, John Feigert, Eric Feldman, Stephanie Gregory, Gary Gross, Robert Hirsch, John Hunter, Ahmad Jajeh, Matt Kalaycio, Ali Khojasteh, Jurgen Kogler, Phil Kuebler, Roger M Lyons, Kenneth Manning, Ann Mohrbacher, Robert O'Donnell, Joel Policzer, Mark Rarick, Allan Saven, Gary Schiller, Larry Schlabach, Andrew Schneider, Karen Seiter, Kevin Troy, Estil A Vance, Allen Yeilding, Furhan Yunus; Venezuela: Angela Rodriguez-M.

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Michallet, M., Maloisel, F., Delain, M. et al. Pegylated recombinant interferon alpha-2b vs recombinant interferon alpha-2b for the initial treatment of chronic-phase chronic myelogenous leukemia: a phase III study. Leukemia 18, 309–315 (2004). https://doi.org/10.1038/sj.leu.2403217

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