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Co-author(s)
Blade, Joan, Hospital Clinic, Barcelona, Spain
Crowley, John, Cancer Research and Biostatistics, Seattle, United States of America
Goldschmidt, Hartmut , University of Heidelberg, Heidelberg, Germany
Hoering, Antje , Cancer Research and Biostatistics, Seattle, United States of America
Jagannath, Sundar , St. Vincent’s Catholic Medical Center, New York, United States of America
Klein, Saskia , Erasmus MC, Rotterdam, Netherlands
Lahuerta, Juan , Hospital Universitario, Madrid, Spain
Laubach, Jacob , Dana-Farber Cancer Institute, Boston, United States of America
Lee, Jae Hoon, Gachon University Medical School, Incheon, South-Korea
Moreau, Philippe, University Hospital Hotel-Dieu, Nantes, France
Morgan, Gareth, Royal Marsden Hospital, Sutton, United Kingdom
Orlowski, Robert , University of Texas/M.D. Anderson Cancer Center, Houston, United States of America
Palumbo, Antonio , Universita di Torino, Torino, Italy
Richardson, Paul , Dana-Farber Cancer Institute, Boston, United States of America
San Miguel, Jésus, Universidad de Salamanca/Hospital Clinico Universitario, Salamanca, Spain
Sezer, Orhan , University of Wurzburg, Würzburg , Germany
Siegel, David , Hackensack University Medical Center/The Cancer Center, Hackensack, United States of America
Sonneveld, Pieter, Erasmus MC, Rotterdam, Netherlands
Szymonifka, Jackie, Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer , Los Angeles, United States of America
Rajkumar, S. Vincent, Mayo Clinic, Rochester, United States of America
Durie, Brian , Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer , Los Angeles, United States of America
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Background: Patients (pts) with multiple myeloma (MM) have increased treatment options with the advent of novel agents such as the IMiDs and bortezomib. However, the disease invariably relapses following use of these drugs and ongoing efforts are targeted to developing new agents for MM. Furthermore, the natural history of MM following the failure of these novel agents is not well understood and is critical for evaluating the potential impact of upcoming experimental therapies on outcome.
Methods: We designed a multicenter, retrospective study that enrolled 291 pts with relapsed MM, from 14 sites (107 pts from US; 115 from Europe; and 69 from Asia). Pts were refractory to Bz, defined as no response to prior Bz-containing regimen or disease progression within 60 days of a Bz-containing regimen. Pts were also relapsed, refractory, intolerant, and/or ineligible, to treatment with an IMiD. Clinical and laboratory data from diagnosis and individual relapses were collected. The date pts satisfied the above entry criteria were defined as time zero (T0).
Results: Median age at diagnosis was 58 years (range 30, 85) and median time from diagnosis to T0 was 3.3 years (0.18, 18.7). Median time to T0 was 4.0, 3.3, and 2.8 for US, European and Asian groups (p=0.006). Following T0, 216 (74%) pts had a treatment recorded, with 93%, 63% and 65% in the US, European and Asian groups receiving therapy respectively. Various regimens were utilized after T0 (median=1; range 0-8), with the US group receiving more regimens following T0 compared to the other two. Minimal response or better was seen to first salvage regimen after T0 in 73 (34%) of pts; 29%, 43% and 29% in the US, Europe and Asian groups respectively. Median overall survival (OS) and event free survival from T0 were 8 mos (95% CI; 6,10) and 5 mos (95% CI; 4,5) for the entire group. Median OS was significantly longer for the US group (13 mos) compared to the European (7 mos) and the Asian (8 mos) groups(p=0.006). EFS was comparable across the groups. There were 22, 13 and 11% of pts who had a transplant after T0 in the three groups respectively. Excluding these pts, median OS was comparable across the three groups, (p=0.18) . In multivariate analysis examining factors affecting OS from T0, serum albumin, B2M and age at diagnosis were prognostically significant (p< 0.05). .
Conclusion: This study confirms the poor outcome of pts once they relapse and become refractory to existing novel agents. Median OS of 8 mos and EFS of 5 mos can be used for comparing the results of ongoing clinical trials in this population. The study also serves to highlight the differences in treatment patterns, including the use of transplant later in the course of disease in US pts, as well as the trend towards the use of multiple salvage regimens, with many in the context of clinical trials.
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