American Society of Blood and Marrow Transplantation, European Society of Blood and Marrow Transplantation, Blood and Marrow Transplant Clinical Trials Network, and International Myeloma Working Group Consensus Conference on Salvage Hematopoietic Cell Transplantation in Patients with Relapsed Multiple Myeloma
Giralt S (1), Garderet L (2), Durie B (3), Cook G (4), Gahrton G (5), Bruno B (6), Hari P (7), Lokhorst H (8), McCarthy P (9), Krishnan A (10), Sonneveld P (11), Goldschmidt H (12), Jagannath S (13), Barlogie B (13), Mateos M (14), Gimsing P (15), Sezer O (16), Mikhael J (17), Lu J (18), Dimopoulos M (19), Mazumder A (20), Palumbo A (21), Abonour R (22), Anderson K (23), Attal M (24), Blade J (25), Bird J (26), Cavo M (27), Comenzo R (28), de la Rubia J (29), Einsele H (30), Garcia-Sanz R (14), Hillengass J (12), Holstein S (9), Johnsen HE (31), Joshua D (32), Koehne G (33), Kumar S (34), Kyle R (34), Leleu X (35), Lonial S (36), Ludwig H (37), Nahi H (5), Nooka A (36), Orlowski R (38), Rajkumar V (34), Reiman A (39), Richardson P (23), Riva E (40), San Miguel J (41), Turreson I (42), Usmani S (43), Vesole D (44), Bensinger W (45), Qazilbash M (38), Efebera Y (46), Mohty M (47), Gasparreto C (48), Gajewski J (49), LeMaistre CF (50), Bredeson C (51), Moreau P (52), Pasquini M (7), Kroeger N (53), Stadtmauer E (54); American Society of Blood and Marrow Transplantation; European Society of Blood and Marrow Transplantation; Blood and Marrow Transplant Clinical Trials Network; International Myeloma Working Group Consensus Conference.
(1) Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center, New York, New York.
(2) Hospital St Antoine, INSERM UMR_S 938, Paris, France.
(3) International Myeloma Foundation, Los Angeles, California.
(4) St. James University Hospital, Leed, United Kingdom.
(5) Karolinska Institute, Huddinge, Sweden.
(6) Universita Degli Studi di Torini, Torino, Italy.
(7) Medical College of Wisconsin, Milwaukee, Wisconsin.
(8) University Medical Center Utrecht, Netherlands.
(9) Roswell Park Cancer Institute, Buffalo, New York.
(10) City of Hope Cancer Center Duarte, California.
(11) Erasmus Medical Center, Rotterdam, Netherlands.
(12) University of Heidelberg, Heidelberg, Germany.
(13) Mount Sinai School of Medicine, New York, New York.
(14) Hospital Universitario de Salamanca, Salamanca, Spain.
(15) Rigshospitalet, Copenhagen, Denmark.
(16) Memorial Sisli Hastanesi, Istanbul, Turkey.
(17) Mayo Clinic Scottsdale, Scottsdale, Arizona.
(18) Peking University Institute of Hematology, People's Hospital, Beijing, Peoples Republic of China.
(19) National and Kapodistrian University of Athens Alexandra Hospital, Athens, Greece.
(20) New York University School of Medicine, New York, New York.
(21)University of Torino, Torino, Italy.
(22) Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana.
(23) Dana Farber Cancer Institute, Harvard University, Boston, Massachusetts.
(24) Institut Claudius Regaud, Toulouse, France.
(25) Hospital Clinic, IDIBAPS, Barcelona, Spain.
(26) University Hospital Bristol, Bristol, United Kingdom.
(27) Seragnoli Institut of Hematology, Bologna University School of Medicine, Bologna, Italy.
(28) Tufts University School of Medicine, Boston, Massachusetts.
(29) Hospital Dr. Pesset, Valencia, Spain.
(30) Klinik der Universität Würzburg, Würzburg, Germany.
(31) Aalborg University Hospital, Aalborg, Denmark.
(32) Royal Prince Alfred Hospital, Sydney University Medical School, Sydney, Australia.
(33) Weill Cornell Medical College, Memorial Sloan Kettering Cancer Center, New York, New York.
(34) Mayo Clinic Rochester, Rochester, Minnesota.
(35) Hospital Claude Huriez, Lille, France.
(36) Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia.
(37) Wilhelminenkrebsforschungsinstituts, Vienna, Austria.
(38) University of Texas MD Anderson Cancer Center, Houston, Texas.
(39) Dalhousie University Medical School, Dalhousie, Nova Scotia, Canada.
(40) Hospital de Clinicas, Montevideo, Uruguay.
(41) Clinica Universidad de Navarra, Navarra, Spain.
(42) Skane University Hospital, Malmo, Sweden.
(43) Levine Cancer Institute, Charlotte, North Carolina.
(44) John Theurer Cancer Center, Hackensack, New Jersey.
(45) Fred Hutchinson Cancer Research Center, Seattle, Washington.
(46) Ohio State University Medical Center, Columbus, Ohio.
(47) University Marie and Pierre Curie, Hospital St Antoine, Paris, France.
(48) Duke University Hospital, Durham, North Carolina.
(49) Oregon Health Sciences University, Portland, Oregon.
(50) Sarah Cannon Research Institute, Nashville, Tennesee.
(51) Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
(52) University Hospital Nantes, Nantes, France.
(53) University Hospital Hamburg, Hamburg, Germany.
(54) University of Pennsylvania Abramson Cancer Center, Philadelphia, Pennsylvania.
In contrast to the upfront setting in which the role of high-dose therapy with autologous hematopoietic cell transplantation (HCT) as consolidation of a first remission in patients with multiple myeloma (MM) is well established, the role of high-dose therapy with autologous or allogeneic HCT has not been extensively studied in MM patients relapsing after primary therapy.
The International Myeloma Working Group together with the Blood and Marrow Transplant Clinical Trials Network, the American Society of Blood and Marrow Transplantation, and the European Society of Blood and Marrow Transplantation convened a meeting of MM experts to: (1) summarize current knowledge regarding the role of autologous or allogeneic HCT in MM patients progressing after primary therapy, (2) propose guidelines for the use of salvage HCT in MM, (3) identify knowledge gaps, (4) propose a research agenda, and (5) develop a collaborative initiative to move the research agenda forward.
After reviewing the available data, the expert committee came to the following consensus statement for salvage autologous HCT: (1) In transplantation-eligible patients relapsing after primary therapy that did NOT include an autologous HCT, high-dose therapy with HCT as part of salvage therapy should be considered standard; (2) High-dose therapy and autologous HCT should be considered appropriate therapy for any patients relapsing after primary therapy that includes an autologous HCT with initial remission duration of more than 18 months; (3) High-dose therapy and autologous HCT can be used as a bridging strategy to allogeneic HCT; (4) The role of postsalvage HCT maintenance needs to be explored in the context of well-designed prospective trials that should include new agents, such as monoclonal antibodies, immune-modulating agents, and oral proteasome inhibitors; (5) Autologous HCT consolidation should be explored as a strategy to develop novel conditioning regimens or post-HCT strategies in patients with short (less than 18 months remissions) after primary therapy; and (6) Prospective randomized trials need to be performed to define the role of salvage autologous HCT in patients with MM relapsing after primary therapy comparing it to "best non-HCT" therapy. The expert committee also underscored the importance of collecting enough hematopoietic stem cells to perform 2 transplantations early in the course of the disease.
Regarding allogeneic HCT, the expert committee agreed on the following consensus statements: (1) Allogeneic HCT should be considered appropriate therapy for any eligible patient with early relapse (less than 24 months) after primary therapy that included an autologous HCT and/or high-risk features (ie, cytogenetics, extramedullary disease, plasma cell leukemia, or high lactate dehydrogenase); (2) Allogeneic HCT should be performed in the context of a clinical trial if possible; (3) The role of postallogeneic HCT maintenance therapy needs to be explored in the context of well-designed prospective trials; and (4) Prospective randomized trials need to be performed to define the role salvage allogeneic HCT in patients with MM relapsing after primary therapy.
CITATION Biol Blood Marrow Transplant. 2015 Dec;21(12):2039-51. doi: 10.1016/j.bbmt.2015.09.016. Epub 2015 Sep 30