title: Maintenance Therapy With Immunomodulatory Drugs in Multiple Myeloma: A Meta-Analysis and Systematic Review.
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.
authors.affiliation: 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).
authors.forename: Yucai
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 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).
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.affiliation: 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).
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.affiliation: 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).
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: 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).
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Wang
authors.affiliation: 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).
authors.forename: Victor T
authors.initials: VT
authors.lastname: Chang
authors.affiliation: 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).
authors.forename: Borje S
authors.initials: BS
authors.lastname: Andersson
authors.affiliation: 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).
authors.forename: Muzaffar H
authors.initials: MH
authors.lastname: Qazilbash
authors.affiliation: 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).
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.affiliation: 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).
authors.forename: James R
authors.initials: JR
authors.lastname: Berenson
authors.affiliation: 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.
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Guan
authors.affiliation: 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.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Wang
mesh_terms: D018572:Disease-Free Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D007239:Infections / Q000209:etiology; D000077269:Lenalidomide; D060046:Maintenance Chemotherapy / Q000379:methods*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000276:immunology* / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000453:epidemiology; D009503:Neutropenia / Q000139:chemically induced; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D012720:Severity of Illness Index; D016019:Survival Analysis; D015996:Survival Rate; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D013923:Thromboembolism / Q000139:chemically induced
chemical_list: D007166:Immunosuppressive Agents; D013792:Thalidomide; D000077269:Lenalidomide