title: Post-Transplant Outcomes in High-Risk Compared with Non-High-Risk Multiple Myeloma: A CIBMTR Analysis.
abstract: Conventional cytogenetics and interphase fluorescence in situ hybridization (FISH) identify high-risk multiple myeloma (HRM) populations characterized by poor outcomes. We analyzed these differences among HRM versus non-HRM populations after upfront autologous hematopoietic cell transplantation (autoHCT). Between 2008 and 2012, 715 patients with multiple myeloma identified by FISH and/or cytogenetic data with upfront autoHCT were identified in the Center for International Blood and Marrow Transplant Research database. HRM was defined as del17p, t(4;14), t(14;16), hypodiploidy (<45 chromosomes excluding -Y) or chromosome 1 p and 1q abnormalities; all others were non-HRM. Among 125 HRM patients (17.5%), induction with bortezomib and immunomodulatory agents (imids) was higher compared with non-HRM (56% versus 43%, P < .001) with similar pretransplant complete response (CR) rates (14% versus 16%, P .1). At day 100 post-transplant, at least a very good partial response was 59% in HRM and 61% in non-HRM (P = .6). More HRM patients received post-transplant therapy with bortezomib and imids (26% versus 12%, P = .004). Three-year post-transplant progression-free (PFS) and overall survival (OS) rates in HRM versus non-HRM were 37% versus 49% (P < .001) and 72% versus 85% (P < .001), respectively. At 3 years, PFS for HRM patients with and without post-transplant therapy was 46% (95% confidence interval [CI], 33 to 59) versus 14% (95% CI, 4 to 29) and in non-HRM patients with and without post-transplant therapy 55% (95% CI, 49 to 62) versus 39% (95% CI, 32 to 47); rates of OS for HRM patients with and without post-transplant therapy were 81% (95% CI, 70 to 90) versus 48% (95% CI, 30 to 65) compared with 88% (95% CI, 84 to 92) and 79% (95% CI, 73 to 85) in non-HRM patients with and without post-transplant therapy, respectively. Among patients receiving post-transplant therapy, there was no difference in OS between HRM and non-HRM (P = .08). In addition to HRM, higher stage, less than a CR pretransplant, lack of post-transplant therapy, and African American race were associated with worse OS. In conclusion, we show HRM patients achieve similar day 100 post-transplant responses compared with non-HRM patients, but these responses are not sustained. Post-transplant therapy appeared to improve the poor outcomes of HRM.
authors: Center for Hematologic Malignancies, The Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
authors: Emma C
authors: EC
authors: Scott
authors: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Parameswaran
authors: P
authors: Hari
authors: Department of Medical Oncology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors: Manish
authors: M
authors: Sharma
authors: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin; Division of Biostatistics, Institute for Health and Society, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Jennifer
authors: J
authors: Le-Rademacher
authors: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin.
authors: Jiaxing
authors: J
authors: Huang
authors: Department of Medicine, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania.
authors: Dan
authors: D
authors: Vogl
authors: Division of BMT, Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan.
authors: Muneer
authors: M
authors: Abidi
authors: Department of Medicine, University of Miami, Miami, Florida.
authors: Amer
authors: A
authors: Beitinjaneh
authors: Department of Medical Oncology, Fox Chase Cancer Center, Temple Health, Philadelphia, Pennsylvania.
authors: Henry
authors: H
authors: Fung
authors: Blood and Marrow Transplantation, University of Kansas Medical Center, Kansas City, Kansas.
authors: Siddhartha
authors: S
authors: Ganguly
authors: Hematology and BMT, University of Kentucky Chandler Medical Center, Lexington, Kentucky.
authors: Gerhard
authors: G
authors: Hildebrandt
authors: Department of Medicine and Oncology, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors: Leona
authors: L
authors: Holmberg
authors: Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic Foundation, Cleveland, Ohio.
authors: Matt
authors: M
authors: Kalaycio
authors: Department of Medicine, Mayo Clinic Rochester, Rochester, Minnesota.
authors: Shaji
authors: S
authors: Kumar
authors: Department of Medicine, Mayo Clinic Rochester, Rochester, Minnesota.
authors: Robert
authors: R
authors: Kyle
authors: Division of Hematology and Oncology, Seidman Cancer Center, University Hospitals Case Medical Center, Cleveland, Ohio.
authors: Hillard
authors: H
authors: Lazarus
authors: Division of Haematology, Royal Adelaide Hospital, Adelaide, South Australia, Australia.
authors: Cindy
authors: C
authors: Lee
authors: Adult Blood and Marrow Stem Cell Transplant Program, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon.
authors: Richard T
authors: RT
authors: Maziarz
authors: Department of Medicine, Dartmouth Hitchcock Medical Center, Lebanon, New Hampshire.
authors: Kenneth
authors: K
authors: Meehan
authors: Department of Medicine, Mayo Clinic Arizona and Phoenix Children's Hospital, Scottsdale, Arizona.
authors: Joseph
authors: J
authors: Mikhael
authors: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors: Taiga
authors: T
authors: Nishihori
authors: Division of Hematology and Oncology, Department of Medicine, UMass Memorial Medical Center, Worchester, Massachusetts.
authors: Muthalagu
authors: M
authors: Ramanathan
authors: Department of Hematology-Medical Oncology, Levine Cancer Institute, Carolinas HealthCare System, Charlotte, North Carolina.
authors: Saad
authors: S
authors: Usmani
authors: Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors: Jason
authors: J
authors: Tay
authors: Myeloma Division, John Theurer Cancer Center at Hackensack UMC, Hackensack, New Jersey.
authors: David
authors: D
authors: Vesole
authors: Division of Bone Marrow Transplant, Seattle Cancer Care Alliance, Seattle, Washington.
authors: Baldeep
authors: B
authors: Wirk
authors: Blood & Marrow Transplantation Program, Division of Hematology/Oncology, Department of Medicine, Greenebaum Cancer Center, University of Maryland, Baltimore, Maryland.
authors: Jean
authors: J
authors: Yared
authors: Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors: Bipin N
authors: BN
authors: Savani
authors: Department of Medicine, Duke University Medical Center, Durham, North Carolina.
authors: Cristina
authors: C
authors: Gasparetto
authors: Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National medical Center, Duarte, California.
authors: Amrita
authors: A
authors: Krishnan
authors: Department of Medicine, Weill Cornell Medical College, New York, New York.
authors: Tomer
authors: T
authors: Mark
authors: Department of Stem Cell Transplantation, MD Anderson Cancer Center, Houston, Texas.
authors: Yago
authors: Y
authors: Nieto
authors: Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin. Electronic address: andsouza@mcw.edu.
authors: Anita
authors: A
authors: D'Souza
mesh_terms: D000328:Adult; D000368:Aged; D020732:Cytogenetic Analysis; D016208:Databases, Factual; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D012189:Retrospective Studies; D018570:Risk Assessment / Q000379:methods*; D016019:Survival Analysis; D014182:Transplantation, Autologous; D016896:Treatment Outcome
keywords: Autologous HSCT; High risk; Maintenance; Multiple myeloma