Paper: Natural History of Multiple Myeloma Relapsing After Therapy with IMiDs and Bortezomib: A Multicenter International Myelo

12/5/2009
Paper: Natural History of Multiple Myel...
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2878 Natural History of Multiple Myeloma Relapsing After Therapy with IMiDs and Bortezomib: A
Multicenter International Myeloma Working Group Study
Oral and Poster Abstracts
Poster Session: Myeloma - Therapy, excluding Transplantation Poster II
Sunday, December 6, 2009, 6:00 PM-8:00 PM
Hall E (Ernest N. Morial Convention Center)
Poster Board II-854
Shaji Kumar1, Joan Blade, M.D.2, John Crowley, PhD3, Harmut Goldschmidt4*, Antje Hoering, Ph.D.3*, Sundar Jagannath,
MD5, Juan José Lahuerta, MD, PhD6*, Jacob Laubach7*, Philippe Moreau, MD8*, Gareth Morgan9*, Robert Z. Orlowski10*,
Antonio Palumbo, M.D.11, Paul Richardson, M.D., Ph.D.7, Jesús F. San Miguel12*, Orhan Sezer13*, David Siegel14, Pieter
Sonneveld15, Jackie Szymonifka3*, S.Vincent Rajkumar, M.D.1* and Brian G M Durie16
1Hematology, Mayo Clinic, Rochester, MN
2Hospital Clinic, IDIBAPS, Barcelona, Spain
3Cancer Research & Biostatistics, Seattle, WA
4Hematology, Oncology, Rheumatology, University of Heidelberg, Heidelberg, Germany
5St. Vincent's Catholic Medical Center, New York, NY
6Hospital 12 de Octubre, Madrid, Spain
7Dana-Farber Cancer Institute, Boston, MA
8University Hospital, Nantes, France
9The Royal Marsden Hospital, Surrey, United Kingdom
10Lymphoma and Myeloma, University of Texas M.D. Anderson Cancer Center, Houston, TX
11Division of Hematology, University of Torino, Torino, Italy
12Hospital Universitario de Salamanca, Salamanca, Spain
13University Hospital Charité, Berlin, Germany
14Hackensack University Medical Center, Hackensack, NJ
15Dept. of Hematology, Erasmus MC, Rotterdam, Netherlands
16Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA
Background: Significant advances have been made in the treatment of myeloma with the introduction of thalidomide, its
analogue, lenalidomide, and the proteasome inhibitor bortezomib. While these new drugs have improved the outcome of
patients with myeloma, the disease still remains incurable. Effectiveness of upcoming new therapies will need to be
assessed in the context of anticipated outcome with the currently available therapies. However, given the rapid pace of
development over the past decade, outcome of patients who have relapsed on the new therapies remain unclear.
Methods: In order to further study this group of patients, we undertook a study of patients who have relapsed on or are
refractory to one of the IMiDs (thalidomide or lenalidomide) as well as bortezomib. A total of 300 cases from 8 sites in the
US, 5 sites in Europe and one site in Asia were identified for this study. Enrolled patients had relapsed and refractory
multiple myeloma, per the EBMT or IMWG response criteria, after at least 2 prior treatments. Patients were refractory to
bortezomib, defined as having no response on a prior bortezomib-containing regimen or experiencing disease progression
within 60 days of a bortezomib-containing regimen. Patients also should have relapsed, refractory, intolerant, and/or
ineligible in the opinion of the investigator, to other therapies, including an IMiD (thalidomide or lenalidomide). Clinical and
laboratory data pertaining to the time of diagnosis and from the time of individual relapses were obtained from the clinical
records. The date patients satisfied the above entry criteria was defined as time zero.
Results: The current analysis includes the first 119 patients with complete data available. The median age at initial
diagnosis was 59 years (range, 31-86 yr); 71% were males. The ISS stage distribution at diagnosis was 33%, 39% and
28% for stages 1, 2, and 3 respectively. 19 patients (37%) had high risk disease by FISH [t(4;14), t(14;16), del17p] or by
cytogenetics [del 13, hypodiploidy]. The median time from diagnosis to time zero was 3.8 yrs (range 0.2-18.7 yr) and the
median reported lines of therapy before time zero was 2. 74% patients had at least 1 autologous stem cell transplant prior
to becoming eligible for the study. Following time zero, 77 (65%) pts had a treatment recorded, including an autologous
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12/5/2009
Paper: Natural History of Multiple Myel...
SCT in 21 (18%), with the treatment regimen starting at a median of 1 month after time zero. A variety of treatment
regimens were utilized beyond time zero (median=1; range 0-7). Thirty-two (27%) patients had a response any time
following time zero, and only 8 had a subsequent response. Response to the first treatment, or supportive care for patients
not treated, recorded following time zero included minor response or stable disease (n=14; 12%), PR (n=17, 14%), and
VGPR or better (n=6, 5%). Patients treated with SCT had a higher rate of PR or better compared to patients receiving other
treatments (85%; 17/20 vs. 26%; 15/57). In a multivariate analysis, the only significant predictor of a PR or better after
time zero was younger age (<60 yrs). The median overall survival (OS) and event free survival (EFS) were 6 mos (95%
CI, 4-7 mos) and 1 month (95% CI,1-2 mos) respectively. In a multivariate analysis normal creatinine predicted for a
better overall survival and having an IgG M protein type predicted for better EFS. A complete analysis from all 300 patients
will be presented at the meeting.
Conclusions: This study confirms the poor outcome of patients once they become relapsed and refractory to agents that
have become the mainstay of myeloma therapy. The findings highlight the incurable nature of the disease and urgent need
to develop newer effective therapeutic agents for this group of patients, who currently do not have effective treatment
options.
Figure: Overall and Event Free survival form the time point they were considered refractory to bortezomib and relapsed,
refractory, or intolerant to thalidomide or lenalidomide (Time zero).
Disclosures: Kumar: CELGENE: Research Funding; MILLENNIUM: Research Funding; BAYER: Research Funding;
GENZYME: Research Funding; NOVARTIS: Research Funding. Jagannath: Merck: Membership on an entity's Board of
Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or advisory committees.
Laubach: Novartis: . Palumbo: Ortho Biotech, Janssen-Cilag: Honoraria; Celgene: Honoraria, Speakers Bureau.
Richardson: Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory
committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory
committees, Speakers Bureau; Johnson and Johnson: Membership on an entity's Board of Directors or advisory
committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers
Bureau; Keryx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership
on an entity's Board of Directors or advisory committees, Speakers Bureau. San Miguel: Millennium: Membership on an
entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or
advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Siegel: Celgene:
Speakers Bureau; Millennium: Speakers Bureau. Sonneveld: Janssen-Cilag: Honoraria. Durie: Celgene: Membership on
an entity's Board of Directors or advisory committees; Millennium: Membership on an entity's Board of Directors or
advisory committees.
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*signifies non-member of ASH
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