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785 Impact of Age on Outcome in Newly Diagnosed Multiple Myeloma Patients Undergoing Upfront Autologous Hematopoietic Cell Transplantation from the Worldwide Network for Blood and Marrow Transplantation Global Study

Program: Oral and Poster Abstracts
Type: Oral
Session: 731. Autologous Transplantation: Clinical and Epidemiological: Role of Autologous Stem Cell Transplantation in Multiple Myeloma and Lymphomas: A Therapeutic Approach
Hematology Disease Topics & Pathways:
Research, Clinical Research, real-world evidence
Monday, December 11, 2023: 11:30 AM

Shohei Mizuno, MD, PhD1*, Luuk Gras Sr., MD, PhD2*, Laurien Baaij3*, Linda Koster3*, Anita D'Souza, MD, MS4, Parameswaran N. Hari, MD, MBBS5, Noel Estrada-Merly, MS6*, Wael Saber, MD, MS7, Andrew J. Cowan, MD8, Minako Iida, MD, PhD9*, Shinichiro Okamoto10*, Hiroyuki Takamatsu, MD, PhD11, Koji Kawamura, MD, PhD/Professor12*, Yoshihisa Kodera, MD13*, Nada Hamad, BSc MSc MBBS FRACP FRCPA14, Bor-Sheng Ko, M.D. Ph.D.15*, Christopher Liam, MRCP16*, KIM Wah HO, MBBS, MRCP17*, Ai Sim Goh18*, S. Keat Tan19*, Alaa M. Elhaddad, MD20, Ali Bazarbachi, MD, PhD21, Brig Qamar Un N Chaudhry, MBBS, FCPS22*, Rozan Alfar23*, Mohamed Amine Bekadja24*, Malek Benakli, MD25*, Cristobal Augusto Frutos, MD26*, Eloisa Riva27*, Sebastian Galeano, MD28*, Francisca Bass, MD29*, Hira Mian, MD30, Arleigh McCurdy, MD, BSc31, Feng Rong Wang32*, Daniel Neumann33*, Mickey Boon Chai Koh, MD, PhD34*, John Snowden, MD35*, Stefan Schönland, MD36*, Donal P McLornan, MD, PhD37*, Patrick J Hayden, MD, PhD38*, Anna Maria Sureda Balari, MD, PhD39, Hildegard T. Greinix, MD40, Mahmoud Aljurf, MD41*, Yoshiko Atsuta, MD, PhD42*, Dietger W. Niederwieser, MD43 and Laurent Garderet, MD, PhD44*

1Aichi Medical University, Nagakute, AIC, Japan
2EBMT Statistical Unit, Leiden, Netherlands
3EBMT Leiden Study Unit, Leiden, Netherlands
4Medical College of Wisconsin, Milwaukee, WI
5Department of Medicine, Medical College of Wisconsin, Milwaukee
6BMT and Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
7CIBMTR® (Center for International Blood and Marrow Transplant Research), National Marrow Donor Program/Be The Match, Minneapolis, MN
8Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA
9Aichi Medical University School of Medicine, Nagakute-cho, Aichi, JPN
10Keio University School of Medicine, Tokyo, JPN
11Kanazawa University, Kanazawa, ISH, Japan
12Hematology, Tottori University Hospital, Yonago, Japan
13Aichi Medical University, Nagakute, AIC, JPN
14Haematology Department, The Kinghorn Cancer Centre, St Vincent's Hospital, Darlinghurst, NSW, Australia
15National Taiwan University Hospital, Taipei, Taiwan
16Hospital Sultanah Aminah, Johor Bahru, Malaysia
17Hospital Ampang, Ampang, Malaysia
18Hospital Pulau Pinang, Pinang, Malaysia
19Hospital Pulau Pinang, Pulau Pinang, Malaysia
20Cairo University, Cairo, EGY
21American University of Beirut Dept. of Medicine, Beirut, Lebanon
22Armed Forces Institute of Transplantation, Rawalpindi, PAK
23King Hussein Cancer Center, Amman, Jordan
24Établissement Hospitalier Universitaire 1 et Novembre, Ahmed Benbella 1 University, Oran, Algeria
25Pierre and Marie Curie Center, Algiers, Algeria
26Instituto de Prevision Social, Asuncion, Paraguay
27Clinical Hospital Dr. Manuel Quintela De Clinicas, Montevideo, Uruguay
28British Hospital, Montevideo, URY
29Intensive Hematology Unit, Hospital Del Salvador, Santiago, Chile
30McMaster University, Hamilton, ON, Canada
31The Ottawa Hospital, Ottawa, ON, Canada
32Peking University, Peking, China
33IMISE, university of Leipzig, Leipzig, Germany
34St George's University Hospitals, London, United Kingdom
35Department of Haematology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom
36Universitätsklinikum Heidelberg, Heidelberg, Germany
37University College London Hospitals NHS Trust, London, United Kingdom
38Trinity College Dublin, St. James's Hospital, Dublin, IRL
39Universitat de Barcelona, Barcelona, Spain
40Medical University Graz, Graz, Austria
41King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
42Japanese Data Center For Hematopoietic Cell Transplantation, Nagakute, Japan
43University of Leipzig, Leipzig, Germany
44Hôpital la pitié salpetriere, Paris, FRA


Induction therapy with proteasome inhibitors and immunomodulatory agents followed by autologous hematopoietic cell transplantation (HCT) is considered standard of care in front line multiple myeloma (MM) treatment. Utilization of autologous HCT is increasing worldwide in younger and older patients in light of improvements in supportive care and infrastructure. However, global perspectives on patterns of patient age and the impact of age on outcomes in this population are scarce. In the current analysis of global registry data, we focused on the age distribution and the association of age with outcomes after HCT worldwide.


Data were provided by the Worldwide Network for Blood and Marrow Transplantation through the European Society for Blood and Marrow Transplantation (EBMT), the Center for International Blood and Marrow Transplantation (CIBMTR), the Australia and New Zealand Transplant and Cellular Therapy Registry (ANZTCTR), the Asian Pacific Blood and Marrow Transplant Group (APBMT), the Eastern Mediterranean Blood and Marrow Transplant Group (EMBMT), the Latin American Bone Marrow Transplant group (LABMT), and the Ottawa hospital myeloma registry. The study included newly diagnosed MM patients transplanted between 2013 and 2017. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS), incidence of relapse, and non-relapse mortality (NRM). The probability of OS and PFS was estimated based on the Kaplan–Meier method and differences were analyzed using the log-rank test. The incidences of relapse and NRM were modeled using the crude cumulative incidence estimator and compared between groups with Gray’s test. Multivariate analyses were performed using Cox (cause-specific) proportional hazards models including a random effect for country. Age at HCT was modeled as a categorical variable (18–39, 40–64, 65–69, 70–74, and ≥75 years). Models further included patient sex, year of HCT, stage of disease at HCT, Karnofsky score, myeloma subclassification, conditioning dosage, interval between diagnosis and HCT, HCT comorbidity index, ISS at diagnosis, and cytogenetic risk score.


In total, 61,725 patients were included in this study; 37,459 (60.1%), 16,217 (26.3%), 3,164 (5.1%), 3,122 (5.1%), 543 (0.9%), 524 (0.8%), 339 (0.5%), 188 (0.3%), and 169 (0.3%) from EBMT, CIBMTR, ANZTCTR, Japan (APBMT), EMBMT, Taiwan (APBMT), LABMT, Ottawa, and Malaysia (APBMT), respectively. The median age at HCT was 60.8 (interquartile range: 54.6–65.8) years. The percentage of patients in the age groups 18–39, 40–64, 65–69, 70–74, and ≥75 years, varied considerably; 2%, 68.9%, 21.8%, 6.5%, and 0.8%, respectively (Table 1). The proportion of <40 years was higher in Malaysia, LABMT, and EMBMT (4–6%) compared to EBMT, CIBMTR, Japan, and ANZTCTR (2%). In contrast, the proportion of patients ≥65 years was higher in EBMT, CIBMTR, ANZTCTR, and Japan (>20%) compared to Malaysia, LABMT, and EMBMT (7–13%). The following patterns were observed in the age groups 18–39, 40–64, 65–69, 70–74, and ≥75 years, respectively. Melphalan 200 mg/m2 for conditioning was used more frequently in younger patients (78.4%, 75.4%, 63.2%, 40.6%, and 28.3%, respectively). In 60.7% of the group ≥75 years, a lower dose of melphalan 140 mg/m2 was chosen. OS was lower with older age (p<0.001) and was 86%, 83%, 81%, 78%, and 75% at 3 years, respectively (Figure and Table 1). PFS was similarly associated with older age (56%, 51%, 50%, 47%, and 45% at 3 years, respectively (p<0.001)). The cumulative incidence of relapse was not significantly different (15%, 16%, 15%, 16%, and 16% at 1 year, respectively (p=0.74)), but the cumulative incidence of NRM was higher with older age (p<0.001) and was 0%, 1%, 2%, 2%, and 4% at 1 year, respectively. On multivariate analysis, older age was associated with lower OS (overall p<0.0001), lower PFS (overall p=0.003), and higher NRM (overall p<0.0001), but not with the risk of relapse (overall p=0.79).


There is considerable global variability in the age distribution of patients receiving HCT. Globally, 2% of patients receiving front line HCT for myeloma are aged <45 and 0.8% are >75 years. Advancing age was a significant risk factor for OS and PFS due to differences in NRM, but even in patients >75 years NRM was very low.

Disclosures: D'Souza: Imbrium, Pfizer, Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Janssen, Prothena: Consultancy; Abbvie, Sanofi, Takeda, TeneoBio, Caelum, Prothena: Research Funding. Cowan: BMS: Consultancy, Research Funding; EUSA: Consultancy; GSK: Consultancy; Harpoon: Research Funding; Janssen: Consultancy, Research Funding; Nektar: Research Funding; Sanofi: Research Funding; Secura Bio: Consultancy; Allogene: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Research Funding. Takamatsu: Janssen: Honoraria; SRL: Consultancy; Bristol-Myers Squibb: Honoraria, Research Funding; Sanofi: Honoraria; Ono: Honoraria. Mian: Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Sanofi: Honoraria; GSK Awards: HHS Research Early Career Award from Hamilton Health Sciences Foundation: Honoraria; Celgene: Honoraria. McCurdy: GSK: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Forus therapeutics: Consultancy, Honoraria; Sanofi: Honoraria; Pfizer: Consultancy, Honoraria; Celgene: Honoraria. Snowden: Kiadis Pharma: Membership on an entity's Board of Directors or advisory committees; Sanofi: Speakers Bureau; advisory boards for MEDAC and Vertex, and clinical trial IDMC membership for Kiadis: Speakers Bureau; Jazz: Speakers Bureau; Janssen: Speakers Bureau; Advisory boards for Vertex: Speakers Bureau; Mallinckrodt: Speakers Bureau. Schönland: Janssen, Prothena, Celgene, Binding Site, Jazz: Other: Travel grant; Janssen, Takeda, Pfizer, Prothena: Honoraria; Prothena, Janssen, Sanofi: Research Funding. McLornan: Abbvie: Honoraria; Novartis: Honoraria; UK ALL RIC TRIAL - DSM board: Other: participation on a data safety monitoring board or advisory board; EBMT Scientific Council Member: Other: Chair of EBMT CMWP; Jazz Pharma: Honoraria; Imago Biosciences: Research Funding. Sureda Balari: Astra Zeneca: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; MSD: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria; Jannsen: Consultancy, Honoraria; Pierre Fabre: Consultancy, Honoraria; GenMab: Consultancy, Honoraria; Kite: Consultancy, Honoraria. Atsuta: Novartis Pharma KK: Speakers Bureau; Meiji Seika Pharma Co, Ltd.: Honoraria; JCR Pharmaceuticals Co., Ltd.: Consultancy; Otsuka Pharmaceutical Co., Ltd: Speakers Bureau; CHUGAI PHARMACEUTICAL CO., LTD.: Speakers Bureau.

*signifies non-member of ASH