TY - JOUR
T1 - Post-Transplant Outcomes in High-Risk Compared with Non–High-Risk Multiple Myeloma
T2 - A CIBMTR Analysis
AU - Scott, Emma C.
AU - Hari, Parameswaran
AU - Sharma, Manish
AU - Le-Rademacher, Jennifer
AU - Huang, Jiaxing
AU - Vogl, Dan
AU - Abidi, Muneer
AU - Beitinjaneh, Amer
AU - Fung, Henry
AU - Ganguly, Siddhartha
AU - Hildebrandt, Gerhard
AU - Holmberg, Leona
AU - Kalaycio, Matt
AU - Kumar, Shaji
AU - Kyle, Robert
AU - Lazarus, Hillard
AU - Lee, Cindy
AU - Maziarz, Richard T.
AU - Meehan, Kenneth
AU - Mikhael, Joseph
AU - Nishihori, Taiga
AU - Ramanathan, Muthalagu
AU - Usmani, Saad
AU - Tay, Jason
AU - Vesole, David
AU - Wirk, Baldeep
AU - Yared, Jean
AU - Savani, Bipin N.
AU - Gasparetto, Cristina
AU - Krishnan, Amrita
AU - Mark, Tomer
AU - Nieto, Yago
AU - D'Souza, Anita
N1 - Funding Information:
The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement 5U24-CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); Grant/Cooperative Agreement 5U10HL069294 from the NHLBI and NCI; contract HHSH250201200016C with Health Resources and Services Administration (DHHS); 2 grants ( N00014-13-1-0039 and N00014-14-1-0028) from the Office of Naval Research ; and grants from Alexion ; * Amgen, Inc. ; Anonymous donation to the Medical College of Wisconsin ; Be The Match Foundation ; * Bristol Myers Squibb Oncology ; * Celgene Corporation ; * Chimerix, Inc. ; Fred Hutchinson Cancer Research Center ; Gamida Cell Ltd. ; Genentech, Inc. ; Genzyme Corporation ; * Gilead Sciences, Inc. ; Health Research, Inc. ; Roswell Park Cancer Institute ; HistoGenetics, Inc. ; Incyte Corporation ; * Jazz Pharmaceuticals, Inc. ; Jeff Gordon Children's Foundation ; Leukemia and Lymphoma Society ; The Medical College of Wisconsin; Merck & Co, Inc. ; Mesoblast ; *Millennium: The Takeda Oncology Co. ; * Miltenyi Biotec ; National Marrow Donor Program ; Neovii Biotech NA, Inc. ; Novartis Pharmaceuticals Corporation ; Onyx Pharmaceuticals ; Optum Healthcare Solutions, Inc. ; Otsuka America Pharmaceutical, Inc. ; Otsuka Pharmaceutical Co., Ltd. ; Oxford Immunotec ; Perkin Elmer, Inc. ; Pharmacyclics ; * Sanofi US ; Seattle Genetics ; Sigma-Tau Pharmaceuticals ; * Spectrum Pharmaceuticals ; St. Baldrick's Foundation ; * Sunesis Pharmaceuticals, Inc. ; Swedish Orphan Biovitrum, Inc. ; Telomere Diagnostics, Inc. ; TerumoBCT ; Therakos, Inc. ; University of Minnesota ; and * WellPoint, Inc. The views expressed in this article do not reflect the official policy or position of the National Institute of Health, the Department of the Navy, the Department of Defense, Health Resources and Services Administration, or any other agency of the U.S. Government. Asterisk denotes corporate members.
Publisher Copyright:
© 2016 The American Society for Blood and Marrow Transplantation
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
AB - 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.
KW - Autologous HSCT
KW - High risk
KW - Maintenance
KW - Multiple myeloma
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U2 - 10.1016/j.bbmt.2016.07.007
DO - 10.1016/j.bbmt.2016.07.007
M3 - Article
C2 - 27496215
AN - SCOPUS:84992035513
SN - 1083-8791
VL - 22
SP - 1893
EP - 1899
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 10
ER -