Yucai Wang1, Fang Yang1, Yan Shen1, Wenwen Zhang1, Jacqueline Wang1, Victor T Chang1, Borje S Andersson1, Muzaffar H Qazilbash1, Richard E Champlin1, James R Berenson1, Xiaoxiang Guan2, Michael L Wang2. 1. Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ (YW, VTC); Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China (FY, YS, WZ, XG); Department of Medicine, University of Chicago, Chicago, IL (JW); Section of Hematology/Oncology, VA New Jersey Health Care System, East Orange, NJ (VTC); Department of Stem Cell Transplantation and Cellular Therapy (BSA, MHQ, REC) and Department of Lymphoma/Myeloma (MLW), The University of Texas MD Anderson Cancer Center, Houston, TX; Institute for Myeloma & Bone Cancer Research, West Hollywood, CA (JRB). 2. Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ (YW, VTC); Department of Medical Oncology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China (FY, YS, WZ, XG); Department of Medicine, University of Chicago, Chicago, IL (JW); Section of Hematology/Oncology, VA New Jersey Health Care System, East Orange, NJ (VTC); Department of Stem Cell Transplantation and Cellular Therapy (BSA, MHQ, REC) and Department of Lymphoma/Myeloma (MLW), The University of Texas MD Anderson Cancer Center, Houston, TX; Institute for Myeloma & Bone Cancer Research, West Hollywood, CA (JRB). miwang@mdanderson.org xguan@nju.edu.cn.
Abstract
BACKGROUND: Immunomodulatory drugs (IMiDs) and proteasome inhibitors have dramatically changed management of multiple myeloma (MM). While MM remains incurable, consolidation and maintenance therapy aimed at improving duration of response can potentially improve survival outcomes. A majority of randomized controlled trials (RCTs) have demonstrated benefit of IMiD-based maintenance therapy in delaying disease progression; however, whether this therapy can lead to improved survival remains controversial. METHODS: PubMed and abstract databases of major hematology and/or oncology meetings were searched for RCTs that studied maintenance therapy with IMiDs in MM. A meta-analysis was conducted to systematically evaluate the impact of IMiD-based maintenance therapy on survival outcomes and serious adverse events associated with the therapy. All statistical tests were two-sided. RESULTS: Eighteen phase 3 RCTs enrolling 7730 patients were included. IMiD-based maintenance therapy statistically significantly prolonged progression-free survival (PFS; hazard ratio (HR) = 0.62, 95% confidence interval (CI) = 0.57 to 0.67, P < .001) but failed to improve overall survival (OS; HR = 0.93, 95% CI = 0.85 to 1.01, P = .082). Stratified analyses demonstrated that both thalidomide and lenalidomide provided PFS but not OS benefit in transplantation as well as nontransplantation settings. IMiD-based maintenance therapy in MM led to a higher risk of grade 3-4 thromboembolism (risk ratio = 2.52, 95% CI = 1.41 to 4.52, P = .002). Thalidomide maintenance therapy increased the risk of peripheral neuropathy; lenalidomide maintenance therapy increased the risks of myelosuppression and second primary hematological malignancies. CONCLUSIONS: Thalidomide- or lenalidomide-based maintenance therapy improves PFS but not OS in MM and increases risks of grade 3-4 adverse events, including thromboembolism, peripheral neuropathy, neutropenia, and infection.
BACKGROUND: Immunomodulatory drugs (IMiDs) and proteasome inhibitors have dramatically changed management of multiple myeloma (MM). While MM remains incurable, consolidation and maintenance therapy aimed at improving duration of response can potentially improve survival outcomes. A majority of randomized controlled trials (RCTs) have demonstrated benefit of IMiD-based maintenance therapy in delaying disease progression; however, whether this therapy can lead to improved survival remains controversial. METHODS: PubMed and abstract databases of major hematology and/or oncology meetings were searched for RCTs that studied maintenance therapy with IMiDs in MM. A meta-analysis was conducted to systematically evaluate the impact of IMiD-based maintenance therapy on survival outcomes and serious adverse events associated with the therapy. All statistical tests were two-sided. RESULTS: Eighteen phase 3 RCTs enrolling 7730 patients were included. IMiD-based maintenance therapy statistically significantly prolonged progression-free survival (PFS; hazard ratio (HR) = 0.62, 95% confidence interval (CI) = 0.57 to 0.67, P < .001) but failed to improve overall survival (OS; HR = 0.93, 95% CI = 0.85 to 1.01, P = .082). Stratified analyses demonstrated that both thalidomide and lenalidomide provided PFS but not OS benefit in transplantation as well as nontransplantation settings. IMiD-based maintenance therapy in MM led to a higher risk of grade 3-4 thromboembolism (risk ratio = 2.52, 95% CI = 1.41 to 4.52, P = .002). Thalidomide maintenance therapy increased the risk of peripheral neuropathy; lenalidomide maintenance therapy increased the risks of myelosuppression and second primary hematological malignancies. CONCLUSIONS:Thalidomide- or lenalidomide-based maintenance therapy improves PFS but not OS in MM and increases risks of grade 3-4 adverse events, including thromboembolism, peripheral neuropathy, neutropenia, and infection.
Authors: Bart Barlogie; Michel Attal; John Crowley; Frits van Rhee; Jackie Szymonifka; Philippe Moreau; Brian G M Durie; Jean-Luc Harousseau Journal: J Clin Oncol Date: 2010-01-19 Impact factor: 44.544
Authors: Philip L McCarthy; Sarah A Holstein; Maria Teresa Petrucci; Paul G Richardson; Cyrille Hulin; Patrizia Tosi; Sara Bringhen; Pellegrino Musto; Kenneth C Anderson; Denis Caillot; Francesca Gay; Philippe Moreau; Gerald Marit; Sin-Ho Jung; Zhinuan Yu; Benjamin Winograd; Robert D Knight; Antonio Palumbo; Michel Attal Journal: J Clin Oncol Date: 2017-07-25 Impact factor: 44.544
Authors: Anna Oberle; Anna Brandt; Minna Voigtlaender; Benjamin Thiele; Janina Radloff; Anita Schulenkorf; Malik Alawi; Nuray Akyüz; Manuela März; Christopher T Ford; Artus Krohn-Grimberghe; Mascha Binder Journal: Haematologica Date: 2017-02-09 Impact factor: 9.941