MedicalResearch.com Interview with:
Philip McCarthy, BA, MD
Professor of Oncology
Director, Blood and Marrow Transplant Program
Roswell Park Cancer Institute
Associate Professor of Medicine
Jacobs School of Medicine and Biomedical Sciences
State University of New York at Buffalo
Buffalo, NY 14263
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. McCarthy: There have been three Phase III studies that examined the role of maintenance lenalidomide after autologous stem cell transplant (ASCT) for newly diagnosed multiple myeloma patients. IFM 2005-02 (France), CALGB 100104 (Alliance, USA), GIMEMA-RVMM-PI-209 (Italy). All three studies had progression free survival (PFS) as their primary endpoint and all demonstrated a superior PFS when compared to placebo or no therapy after ASCT. However only the CALGB 100104 study demonstrated a statistically superior overall survival (OS). Thus, a meta-analysis was necessary to assess the effect of post-ASCT lenalidomide maintenance on overall survival. This study utilized a pooled analysis of updated primary-source patient data from all three studies after the primary efficacy analyses had been conducted. The meta-analysis demonstrated that there is a statistically superior OS (P value=0.001, HR=0.74 (0.62-0.89)), Median OS for no maintenance or placebo was 86 months and the median OS for lenalidomide had not been reached. The median OS for lenalidomide treatment arm was extrapolated to be 116 months based on median of the control arm and HR (median, 86 months; HR = 0.74). Thus, there is a 26% reduction in the risk of death which is an estimated 2.5 year increase in median OS. There is an increased incidence of second primary malignancies with lenalidomide maintenance when compared to placebo but this risk is less than the risk of dying when not receiving lenalidomide.
MedicalResearch.com: What should readers take away from your report?
Dr. McCarthy: Lenalidomide maintenance is feasible for long-term disease control after ASCT for newly diagnosed multiple myeloma patients. The overall survival benefit of lenalidomide maintenance outweighs the risk of developing an hematologic or solid tumor SPM. Lenalidomide maintenance after induction therapy and ASCT for newly diagnosed multiple myeloma can be considered a standard of care. The IFM 05-02 study discontinued lenalidomide with the SPM signal but the Italian and US groups did not stop lenalidomide. The IFM OS HR was 0.91 (0.72-1.15) or a 9% reduction in the risk of death. The CALGB 100104 OS HR was 0.56 (0.42-0.76) or a 44% reduction in the risk of death, The GIMEMA OS HR was 0.66 (0.34-1.26) or a 36% reduction in the risk of death. As noted above, the CALGB (Alliance) and the GIMEMA studies continued lenalidomide until progression of multiple myeloma.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Dr. McCarthy: Understanding the role of minimal residual disease detection and immune reconstitution after ASCT is necessary to continue to improve on overall survival
We must develop early endpoints as surrogates for long-term outcome and overall survival. Otherwise, trials may continue for 10 years or longer! This is great for our patients but it makes it difficult to study new agents for improved overall survival, long term disease control and even cure of multiple myeloma. It will be very important to study agents such as anti-CD38 antibodies (daratumumab, isatuximab), the anti-SLAMF-7 (CS-1) antibody elotuzumab, Checkpoint inhibitors (too many to list!), proteasome inhibitors, histone deacetylase inhibitors and other novel compounds to determine if they can improve upon the activity of single agent lenalidomide. The GIMEMA study did not show a large increase in SPMs. It utilized a schedule of lenalidomide 3 weeks of therapy and one week no therapy every 28 days (21/28). It will be important to determine if this schedule results in a decrease in SPMs. Another GIMEMA study examining lenalidomide (21/28) versus lenalidomide (21/28)and prednisone will be an important study to analyze the incidence of SPMs but it does not have a true control. The UK Myeloma XI study will be very important for study as it examines lenalidomide maintenance of 21/28 days versus no maintenance.
MedicalResearch.com: Is there anything else you would like to add?
Dr. McCarthy: This is a very exciting time for multiple myeloma patients. There a multiple new drugs which can be combined to someday result in long term disease control and hopefully cure of this disease.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Citation: Lenalidomide maintenance after high-dose melphalan and autologous stem cell transplant in multiple myeloma : A meta-analysis of overall survival
2016 ASCO Annual Meeting
Abstract No: 8001
J Clin Oncol 34, 2016 (suppl; abstr 8001)
Author(s): Michel Attal, Antonio Palumbo, Sarah A. Holstein, Valerie Lauwers-Cances, Maria Teresa Petrucci, Paul G. Richardson, Cyrille Hulin, Patrizia Tosi, Kenneth Carl Anderson, Denis Caillot, Valeria Magarotto, Philippe Moreau, Gerald Marit, Zhinuan Yu, Philip L. McCarthy; CHU Purpan, Toulouse, France; Department of Hematology, University of Torino, Torino, Italy; Roswell Park Cancer Institute, Buffalo, NY; University La Sapienza, Rome, Jersey; Department of Hematology, Sapienza University of Rome, Rome, Italy; Dana-Farber Cancer Institute, Boston, MA; Hematology Department, University Hospital, Nancy, France; Seràgnoli Institute of Hematology and Medical Oncology, Bologna University, Bologna, Italy; Dijon University Hospital Center, Dijon, France; Myeloma Unit, Division of Hematology, University of Torino, AOU S. Giovanni Battista, Torino, Italy; University Hospital Hotel-Dieu, Nantes, France; Service d’Hématologie Clinique, Hôpital du Haut Leveque CHU de Bordeaux, Bordeaux, France; Celgene Corporation, Summit, NJ
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