Author
Michel Attal
Bio: Michel Attal is an academic researcher from Centre Hospitalier Universitaire de Toulouse. The author has contributed to research in topics: Transplantation & Multiple myeloma. The author has an hindex of 10, co-authored 14 publications receiving 3549 citations.
Topics: Transplantation, Multiple myeloma, Lenalidomide, Population, Bortezomib
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TL;DR: Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma.
Abstract: BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation is a standard treatment for young patients with multiple myeloma. Residual disease is almost always present after transplantation and is responsible for relapse. This phase 3, placebocontrolled trial investigated the efficacy of lenalidomide maintenance therapy after transplantation. METHODS:We randomly assigned 614 patients younger than 65 years of age who had nonprogressive disease after first-line transplantation to maintenance treatment with either lenalidomide (10 mg per day for the first 3 months, increased to 15 mg if tolerated) or placebo until relapse. The primary end point was progression-free survival. RESULTS:Lenalidomide maintenance therapy improved median progression-free survival (41 months, vs. 23 months with placebo; hazard ratio, 0.50; P<0.001). This benefit was observed across all patient subgroups, including those based on the β 2- microglobulin level, cytogenetic profile, and response after transplantation. With a median follow-up period of 45 months, more than 70% of patients in both groups were alive at 4 years. The rates of grade 3 or 4 peripheral neuropathy were similar in the two groups. The incidence of second primary cancers was 3.1 per 100 patient-years in the lenalidomide group versus 1.2 per 100 patient-years in the placebo group (P = 0.002). Median event-free survival (with events that included second primary cancers) was significantly improved with lenalidomide (40 months, vs. 23 months with placebo; P<0.001). CONCLUSIONS:Lenalidomide maintenance after transplantation significantly prolonged progression-free and event-free survival among patients with multiple myeloma. Four years after randomization, overall survival was similar in the two study groups. (Funded by the Programme Hospitalier de Recherche Clinique and others; ClinicalTrials.gov number, NCT00430365.) Copyright © 2012 Massachusetts Medical Society.
996 citations
TL;DR: Among adults with multiple myeloma, RVD therapy plus transplantation was associated with significantly longer progression‐free survival than RVD Therapy alone, but overall survival did not differ significantly between the two approaches.
Abstract: BackgroundHigh-dose chemotherapy plus autologous stem-cell transplantation has been the standard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age. However, promising data on the use of combination therapy with lenalidomide, bortezomib, and dexamethasone (RVD) in this population have raised questions about the role and timing of transplantation. MethodsWe randomly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (350 patients) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (350 patients). Patients in both groups received maintenance therapy with lenalidomide for 1 year. The primary end point was progression-free survival. ResultsMedian progression-free survival was significantly longer in the group that underwent transplantation than in the group that received RVD alone (50 months vs. 36 months; adjusted hazar...
817 citations
National and Kapodistrian University of Athens1, Mayo Clinic2, Monash University3, Cross Cancer Institute4, University of Bologna5, University of Tübingen6, University of Calgary7, La Roche College8, Katholieke Universiteit Leuven9, St Bartholomew's Hospital10, University of Coimbra11, Chonnam National University12, University Health Network13, Autonomous University of Barcelona14, Peking Union Medical College15, Queen Elizabeth II Health Sciences Centre16, Winterthur Museum, Garden and Library17, Harvard University18, University of Nantes19, Centre Hospitalier Universitaire de Toulouse20, Celgene21
TL;DR: Continuous lenalidomide-dexamethasone given until disease progression was associated with a significant improvement in progression-free survival, with an overall survival benefit at the interim analysis, among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation.
Abstract: Background The combination melphalan–prednisone–thalidomide (MPT) is considered a standard therapy for patients with myeloma who are ineligible for stem-cell transplantation. However, emerging data on the use of lenalidomide and low-dose dexamethasone warrant a prospective comparison of the two approaches. Methods We randomly assigned 1623 patients to lenalidomide and dexamethasone in 28-day cycles until disease progression (535 patients), to the same combination for 72 weeks (18 cycles; 541 patients), or to MPT for 72 weeks (547 patients). The primary end point was progression-free survival with continuous lenalidomide–dexamethasone versus MPT. Results The median progression-free survival was 25.5 months with continuous lenalidomide–dexamethasone, 20.7 months with 18 cycles of lenalidomide–dexamethasone, and 21.2 months with MPT (hazard ratio for the risk of progression or death, 0.72 for continuous lenalidomide–dexamethasone vs. MPT and 0.70 for continuous lenalidomide–dexamethasone vs. 18 cycles of len...
651 citations
university of lille1, University of Southern Denmark2, University of Calgary3, University of Wolverhampton4, Karolinska Institutet5, University of Melbourne6, Heidelberg University7, National University of Ireland, Galway8, University of Alberta9, Harvard University10, Centre Hospitalier Universitaire de Toulouse11, University of Caen Lower Normandy12, University of Paris13, Genmab14, Janssen Pharmaceutica15
TL;DR: Among patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation, the risk of disease progression or death was significantly lower among those who received daratumumab plus lenalidomide and dexamethasone than among thosewho received lenalidmide and Dexameth asone alone.
Abstract: Background Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought...
609 citations
Erasmus University Medical Center1, Universitaire Ziekenhuizen Leuven2, University of Paris3, Curie Institute4, Institut Français5, VU University Amsterdam6, La Roche College7, Université libre de Bruxelles8, Cliniques Universitaires Saint-Luc9, Albert Schweitzer Hospital10, French Institute of Health and Medical Research11, Princeton University12, Janssen Pharmaceutica13
TL;DR: D-VTd before and after autologous stem-cell transplantation improved depth of response and progression-free survival with acceptable safety and CASSIOPEIA is the first study showing the clinical benefit of daratumumab plus standard of care in transplant-eligible patients with newly diagnosed multiple myeloma.
569 citations
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Mayo Clinic1, University of Navarra2, Harvard University3, Cedars-Sinai Medical Center4, Memorial Sloan Kettering Cancer Center5, Emory University6, National and Kapodistrian University of Athens7, University of Turin8, Mount Sinai Hospital9, University of Texas MD Anderson Cancer Center10, Heidelberg University11, Alfred Hospital12, University Health System13, Carolinas Healthcare System14, University of Bologna15, Aalborg University16, Dalhousie University17, Erasmus University Rotterdam18, Roswell Park Cancer Institute19, Columbia University20, University of Toulouse21
TL;DR: Several aspects of disease response assessment are clarified, along with endpoints for clinical trials, and future directions for disease response assessments are highlighted, to allow uniform reporting within and outside clinical trials.
Abstract: Treatment of multiple myeloma has substantially changed over the past decade with the introduction of several classes of new effective drugs that have greatly improved the rates and depth of response. Response criteria in multiple myeloma were developed to use serum and urine assessment of monoclonal proteins and bone marrow assessment (which is relatively insensitive). Given the high rates of complete response seen in patients with multiple myeloma with new treatment approaches, new response categories need to be defined that can identify responses that are deeper than those conventionally defined as complete response. Recent attempts have focused on the identification of residual tumour cells in the bone marrow using flow cytometry or gene sequencing. Furthermore, sensitive imaging techniques can be used to detect the presence of residual disease outside of the bone marrow. Combining these new methods, the International Myeloma Working Group has defined new response categories of minimal residual disease negativity, with or without imaging-based absence of extramedullary disease, to allow uniform reporting within and outside clinical trials. In this Review, we clarify several aspects of disease response assessment, along with endpoints for clinical trials, and highlight future directions for disease response assessments.
1,681 citations
TL;DR: In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk–benefit profile.
Abstract: Background Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma Methods We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group) The primary end point was progression-free survival Results Progression-free survival was significantly improved with carfilzomib (median, 263 months, vs 176 months in the control group; hazard ratio for progression or death, 069; 95% confidence interval [CI], 057 to 083; P = 00001) The median overall survival was not reached in either group at the interim analysis The Kaplan–Meier 24-month overall survival rates were 733% and 650% in the carfilzomib and control groups, respectively (hazard ratio for death, 079; 95% CI, 063 to 099; P = 004) The rates of overall response (partial response or better) were 871% and 667% in the carfilzomib and control groups, respectively (P<0001; 318% and 93% of patients in the respective groups had a complete response or better; 141% and 43% had a stringent complete response) Adverse events of grade 3 or higher were reported in 837% and 807% of patients in the carfilzomib and control groups, respectively; 153% and 177% of patients discontinued treatment owing to adverse events Patients in the carfilzomib group reported superior health-related quality of life Conclusions In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk–benefit profile (Funded by Onyx Pharmaceuticals; ClinicalTrialsgov number, NCT01080391)
1,034 citations
Roswell Park Cancer Institute1, Duke University2, Ohio State University3, Wake Forest University4, Memorial Sloan Kettering Cancer Center5, Harvard University6, University of Pennsylvania7, University of Minnesota8, Washington University in St. Louis9, University of Florida10, University of Wisconsin-Madison11, University of Chicago12, State University of New York Upstate Medical University13, Icahn School of Medicine at Mount Sinai14, Oregon Health & Science University15, University of North Carolina at Chapel Hill16, University of California, San Francisco17, University of Texas MD Anderson Cancer Center18, Medical College of Wisconsin19
TL;DR: Lenalidomide maintenance therapy, initiated at day 100 after hematopoietic stem-cell transplantation, was associated with more toxicity and second cancers but a significantly longer time to disease progression and significantly improved overall survival among patients with myeloma.
Abstract: Background Data are lacking on whether lenalidomide maintenance therapy prolongs the time to disease progression after autologous hematopoietic stem-cell transplantation in patients with multiple myeloma. Methods Between April 2005 and July 2009, we randomly assigned 460 patients who were younger than 71 years of age and had stable disease or a marginal, partial, or complete response 100 days after undergoing stem-cell transplantation to lenalidomide or placebo, which was administered until disease progression. The starting dose of lenalidomide was 10 mg per day (range, 5 to 15). Results The study-drug assignments were unblinded in 2009, when a planned interim analysis showed a significantly longer time to disease progression in the lenalidomide group. At unblinding, 20% of patients who received lenalidomide and 44% of patients who received placebo had progressive disease or had died (P<0.001); of the remaining 128 patients who received placebo and who did not have progressive disease, 86 crossed over to ...
996 citations
TL;DR: The addition of ixazomib to a regimen of lenalidomide and dexamethasone was associated with significantly longer progression-free survival; the additional toxic effects with this all-oral regimen were limited.
Abstract: BackgroundIxazomib is an oral proteasome inhibitor that is currently being studied for the treatment of multiple myeloma. MethodsIn this double-blind, placebo-controlled, phase 3 trial, we randomly assigned 722 patients who had relapsed, refractory, or relapsed and refractory multiple myeloma to receive ixazomib plus lenalidomide–dexamethasone (ixazomib group) or placebo plus lenalidomide–dexamethasone (placebo group). The primary end point was progression-free survival. ResultsProgression-free survival was significantly longer in the ixazomib group than in the placebo group at a median follow-up of 14.7 months (median progression-free survival, 20.6 months vs. 14.7 months; hazard ratio for disease progression or death in the ixazomib group, 0.74; P=0.01); a benefit with respect to progression-free survival was observed with the ixazomib regimen, as compared with the placebo regimen, in all prespecified patient subgroups, including in patients with high-risk cytogenetic abnormalities. The overall rates of...
821 citations
TL;DR: Among adults with multiple myeloma, RVD therapy plus transplantation was associated with significantly longer progression‐free survival than RVD Therapy alone, but overall survival did not differ significantly between the two approaches.
Abstract: BackgroundHigh-dose chemotherapy plus autologous stem-cell transplantation has been the standard treatment for newly diagnosed multiple myeloma in adults up to 65 years of age. However, promising data on the use of combination therapy with lenalidomide, bortezomib, and dexamethasone (RVD) in this population have raised questions about the role and timing of transplantation. MethodsWe randomly assigned 700 patients with multiple myeloma to receive induction therapy with three cycles of RVD and then consolidation therapy with either five additional cycles of RVD (350 patients) or high-dose melphalan plus stem-cell transplantation followed by two additional cycles of RVD (350 patients). Patients in both groups received maintenance therapy with lenalidomide for 1 year. The primary end point was progression-free survival. ResultsMedian progression-free survival was significantly longer in the group that underwent transplantation than in the group that received RVD alone (50 months vs. 36 months; adjusted hazar...
817 citations