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Blood, 15 November 2007, Vol. 110, No. 10, pp. 3557-3560.
Prepublished online as a Blood First Edition Paper on August 9, 2007; DOI 10.1182/blood-2006-08-036947.


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Submitted August 2, 2006
Accepted June 20, 2007

Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial

Paul G. Richardson*, Pieter Sonneveld, Michael Schuster, David Irwin, Edward Stadtmauer, Thierry Facon, Jean-Luc Harousseau, Dina Ben-Yehuda, Sagar Lonial, Hartmut Goldschmidt, Donna Reece, Jesus San Miguel, Joan Blade, Mario Boccadoro, Jamie Cavenagh, Melissa Alsina, S Vincent Rajkumar, Martha Lacy, Andrzej Jakubowiak, William Dalton, Anthony Boral, Dixie-Lee Esseltine, David Schenkein, and Kenneth C Anderson

Dana-Farber Cancer Institute, Boston, MA, United States
University Hospital Rotterdam, Rotterdam, Netherlands
NY-Presbyterian Hospital, New York, NY, United States
Alta Bates Cancer Center, Berkeley, CA, United States
University PA Cancer Center, Philadelphia, PA, United States
Hosp Claude Huriez, Lille, France
Hotel Dieu, CHU de Nantes, Nantes, France
Hadassah University Hospital, Jerusalem, Israel
Emory University School of Medicine, Atlanta, GA, United States
University Heidelberg, Heidelberg, Germany
Princess Margaret Hospital, Toronto, Canada
Hospital Univ Salamanca, Salamanca, Spain
University of Barcelona, Barcelona, Spain
University of Torino, Torino, Italy
St. Bartholomew's Hospital, London, United Kingdom
H. Lee Moffitt Cancer Center, Tampa, FL, United States
Mayo Clinic, Rochester, MN, United States
University of Michigan Comprehensive Cancer Center, Ann Arbor, MI, United States
Millennium Pharmaceuticals, Inc., Cambridge, MA, United States
Genentech, Inc., San Francisco, CA, United States

* Corresponding author; email: paul_richardson{at}dfci.harvard.edu.

Initial analysis of the Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial of relapsed multiple myeloma patients showed significantly longer time to progression, higher response rate, and improved survival with single-agent bortezomib vs high-dose dexamethasone. In this updated analysis (median follow-up: 22 months) survival was assessed in both arms, and efficacy updated for the bortezomib arm. Median survival was 29.8 months for bortezomib vs 23.7 months for dexamethasone, a 6-month benefit, despite substantial crossover from dexamethasone to bortezomib. Overall/complete response rates with bortezomib were 43% and 9%, respectively; among responding patients, 56% improved response with longer therapy beyond initial response, leading to continued improvement in overall quality of response. Higher response quality (100% M-protein reduction) was associated with longer response duration; response duration was not associated with time to response. These data confirm the activity of bortezomib and support extended treatment in relapsed multiple myeloma patients tolerating therapy. This study is registered at http://clinicaltrials.gov (Study ID NCT00048230).


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