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4733 Validation of the EBMT Multiple Myeloma Early Relapse Score within Worldwide Network for Blood and Marrow Transplantation (WBMT) Global Study

Program: Oral and Poster Abstracts
Session: 654. Multiple Myeloma: Pharmacologic Therapies: Poster III
Hematology Disease Topics & Pathways:
Research, Adult, Clinical Research, Plasma Cell Disorders, Diseases, Registries, Lymphoid Malignancies, Study Population, Human
Monday, December 9, 2024, 6:00 PM-8:00 PM

Meral Beksac, MD1, Simona Iacobelli2*, Luuk Gras3*, Linda Koster4*, Laurien Baaij4*, Nada Hamad, MBBS, MSc, BSc5, Anita D'Souza, MD6, Noel Estrada-Merly, MS7*, Parameswaran N. Hari, MD, MBBS8, Andrew J. Cowan, MD9, Wael Saber, MD, MS10, Minako Iida, MD, PhD11*, Shinichiro Okamoto12*, Hiroyuki Takamatsu, MD, PhD13, Shohei Mizuno, MD, PhD14*, Koji Kawamura, MD, PhD15*, Yoshihisa Kodera, MD16*, Bor-Sheng Ko, M.D. Ph.D.17, Christopher Liam, MRCP18*, KIM Wah HO, MBBS, MRCP19*, A Sim Goh, MD20*, S Keat Tan21*, Alaa M. Elhaddad, MD22, Ali Bazarbachi, MD, PhD23, Qamar-un-Nisa Chaudhry24*, Rozan Alfar25*, Mohamed Amine Bekadja26*, Malek Benakli, MD27*, Cristobal Augusto Frutos Ortiz, MD28*, Eloisa Riva, MD, MEd29, Sebastian Galeano, MD30, Francisca Bass, MD31*, Hira Mian, MD32, Arleigh McCurdy, MD33, Feng Rong Wang34*, Meng Lv, MD, PhD35, Daniel Neumann36*, Mickey Boon Chai Koh, MD, PhD37*, John Snowden, MD38*, Stefan O. Schönland, MD39*, Donal P McLornan, MD, PhD40*, Patrick J Hayden, MD, PhD41*, Damiano Rondelli, MD42*, Hildegard Greinix43*, Mahmoud Aljurf44*, Yoshiko Atsuta45*, Ana Sureda Balari46, Dietger W. Niederwieser, MD47 and Laurent Garderet, MD, PhD48*

1Hematology, Istinye University Ankara Liv Hospital, Ankara, Turkey
2Centro Di Biostatistica E Bioinformatica Università Tor Vergata, Rome, ITA
3EBMT, Leiden, Netherlands
4EBMT Leiden Study Unit, Leiden, Netherlands
5School of Clinical Medicine, Faculty of Medicine and Health, The University of New South Wales, Sydney, NSW, Australia
6Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
7BMT and Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
8The Medical College of Wisconsin, Brookfield, WI
9University of Washington, Seattle, WA
10Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI
11Aichi Medical University School of Medicine, Nagakute-cho, Aichi, JPN
12Keio University School of Medicine, Tokyo, JPN
13Department of Hematology, Kanazawa University, Kanazawa, Japan
14Division of Hematology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi, Japan
15Division of Hematology and Clinical Laboratory Medicine, Tottori University Hospital, Yonago, Japan
16Aichi Medical University, Nagakute, AIC, JPN
17Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
18Hospital Sultanah Aminah, Johor Bahru, Malaysia
19Hospital Ampang, Ampang, Malaysia
20Penang General Hospital, Penang, Malaysia
21Hospital Pulau Pinang, Pulau Pinang, Malaysia
22Children Cancer Hospital Egypt - 57357, Cairo, Egypt
23American University of Beirut Dept. of Medicine, Beirut, Lebanon
24AFBMTC/NIBMT, Rawalpindi, Pakistan
25King Hussein Cancer Center, Amman, Jordan
26EHU, Oran, Algeria
27Pierre and Marie Curie Center, Algiers, Algeria
2825Hospital Central Del Instituto De Prevision Social, Asuncion, Paraguay
29Hematology, Hospital de Clinicas, Montevideo, Uruguay
30Bone marrow transplant unit, British Hospital, Montevideo, Montevideo, Uruguay
31Intensive Hematology Unit, Hospital Del Salvador, Santiago, Chile
32McMaster University, Hamilton, ON, Canada
33The Ottawa Hospital, Ottawa, ON, Canada
34Peking University, Peking, China
35Peking University People's Hospital, Beijing, China
36IMISE, university of Leipzig, Leipzig, Germany
37St George's University Hospitals, London, United Kingdom
38BSBMTCT, Department of Haematology, Sheffield Teaching Hospitals NHS Trust, Sheffield, United Kingdom
39Medical Department V, Amyloidosis Center,, University of Heidelberg, Heidelberg, Germany
40Department of Haematology, University College London Hospitals NHS Trust, London, ENG, United Kingdom
41Trinity College Dublin, St. James's Hospital, Dublin, IRL
42Division of Hematology/Oncology, University of Illinois College of Medicine, Chicago, IL
43Medical University of Graz, Graz, Austria
44Department of Hematology, Stem Cell Transplantation, and Cellular Therapy, Cancer Center of Excellence, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
4541Japanese Data Center for Hematopoietic Cell Transplantation, Department of Registry Science for Transplant and Cellular Therapy, Aichi Medical University School of Medicine, Nagakute, Japan
46Instituto Catalán de Oncología - Hospital Duran i Reynals, Barcelona, Spain
47Universitaetsklinikum Leipzig Aor, Leipzig, Germany
48Department of Hematology, Hopital Saint Antoine, Paris, FRA

Rationale: Early relapse (ER) within 12 months of Autologous Hematopoietic Stem Cell Transplantation (AHCT) is currently accepted as functional high risk among patients diagnosed with Multiple Myeloma (MM). Efforts to predict ER has led to different risk scores developed by CIBMTR, GIMEMA and EBMT. CIBMTR and GIMEMA score integrates parameters not always available (bone marrow plasma cell percentage prior to AHCT, lambda light chain, FISH and LDH), whereas the EBMT score includes very simple factors ISS (at diagnosis), performance and disease status (prior to AHCT) (Beksac et al BMT 2023). EBMT ER score was developed using data obtained from patients aged 40-70 with a first AHCT in mainly European transplantation centers. This retrospective study aims to validate the EBMT ER score using data from a worldwide cohort of AHCT MM patients. This large population differs from the one used in the original paper, by age range, the number of countries and ethnicities, features in favor of suitability for external validation.

Methods: We selected patients from the WBMT study, a collaboration of five MM transplantation registries around the world. Only registries with data available on all components of the EBMT score were selected. Patients included in WAUSTIM had a first AHCT between 2013-2017. EBMT data within this current study belonged to only 2013 which was not included in the original study. We used Cox proportional hazards regression and the c-index to measure the predictive discriminative performance of the EBMT ER score.

Results: In total 14,924 patients (EBMT (4.1%), CIBMTR (79%), Australia and New Zealand (2.8.%), Japan (14%) and EMBMT (0.2%) were included. Median age at AHCT was 61(25-83) years. IgG (56%), IgA (21%) and light chain (21%). Disease status at the time of AHCT was CR (16%), VGPR (39%), PR (39%), SD/MR (6%), Rel/Prog (0.3%): ISS at diagnosis was I/II/III: 38/36/27%; Karnofsky score prior to AHCT-1: ≤70/80/90/100: 12/29/41/18 %. Cytogenetic risk was standard/high (t(4;14),t(14;16),17pdel) in 69%/31% of those with data available (not available in 17%). 81%/16% received Mel200/Mel140. Maintenance treatment was unknown for 89%. EBMT ER score distribution was: 0/1/2/3/4: 18%/32%/31%/14%/3.5%.

Within the Mel200 only population restricted to the 40-70 age limit (as in the original study), after a median FU of 48 months 12-month PFS (PFS-12) was 84% (95% CI 83-84%) with an ER incidence of 14.7%. which is similar to that observed in the original EBMT study (Mel200 training: 14.7%, Mel200 validation: 11.6%, Mel140: 16.9%). The score 0/1/2/3/4 distribution was: 19%/34%/31%/13%/3.2%. Thus the prevalence of scores 0-4 within the original and the current study are similar as well. PFS-12 (95% CI) according to scores were as follows: score 0: 90 (89-91); score 1: 86 (85-87); score 2: 83 (82-84); score 3: 78 (76-80); score 4: 69 (64-74) resulting with HRs vs score 0: score 1: 1.42; score 2: 1.75; score 3: 2.32; score 4: 3.69 (all p values<0.001. The c-index was 0.58 without and 0.61 with cytogenetic risk included. EBMT ER score acts similarly within this worldwide population with a clear separation of curves between scores 0-4. Cytogenetic high risk vs standard risk HR: 1.88 (95% CI: 1.69-2.09) among Mel200 and 1.81(95% CI: 1.65-1.98) were among the whole population(p-value<0.001). Comparison of the original study HRs and score points with the current analysis will be presented at the meeting.

Similar analysis performed among the whole population not limited to age or conditioning regimen intensity, resulted with highly similar PFS-12 ranging between 90-69% for scores 0-4 with HRs 1.39-3.49 (scores 1-4, all p-values <0.001; high vs standard risk HR: 1.81; C index: 0.58 without cytogenetic, and 0.61 with cytogenetic).

Conclusion: In a population from various parts of the world, we have been able to validate the EBMT ER score among both Mel200 and Mel140 conditioned myeloma patients with a wider range of age at AHCT-1. Although the cytogenetic risk score provided additional predictive value in the original and current study, it had no modification effect on the EBMT ER score. Due to high rate of maintenance data missingness, we could not investigate the role of the score when patients were continued to be treated after AHCT. Based on our findings, EBMT ER score is a predictive tool for recognition of functional high risk MM patients at the time of AHCT-1.

Disclosures: Beksac: Amgen: Speakers Bureau; Sanofi: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; GSK: Research Funding; Menarini: Consultancy, Other: advisory; Bristol Myers Squibb: Speakers Bureau; Janssen: Research Funding, Speakers Bureau. D'Souza: Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Caelum: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Kedrion: Membership on an entity's Board of Directors or advisory committees; Abbvie: Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Prothena: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Regeneron: Research Funding; Takeda: Research Funding. Hari: Obsidian Biotherapeutics: Ended employment in the past 24 months; Obsidian Therapeutics: Current Employment. Cowan: Adaptive Biotechnologies: Consultancy, Research Funding; Regeneron: Research Funding; Abbvie: Research Funding; BMS: Consultancy, Research Funding; Juno/Celgene: Research Funding; IgM biosciences: Research Funding; Nektar: Research Funding; Harpoon: Research Funding; Caelum: Research Funding; HopeAI: Consultancy, Current holder of stock options in a privately-held company; Sanofi: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sebia: Consultancy. Takamatsu: Sanofi: Honoraria; SRL: Consultancy; Janssen: Honoraria; Adaptive Biotechnologies: Consultancy; Ono: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding. Mizuno: Hayashikane Sangyo: Research Funding; Janssen pharmaceutical: Honoraria. Bazarbachi: Caribou: Honoraria; Amgen: Honoraria; Biologix: Research Funding; Takeda: Honoraria; Jansen: Honoraria, Research Funding; Pfizer: Research Funding; Roche: Honoraria, Research Funding. Mian: BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees. McLornan: Imago Biosciences: Research Funding; Abbvie: Honoraria; Jazz Pharma: Honoraria; Novartis: Honoraria. Rondelli: Vertex Pharmaceuticals: Honoraria. Sureda Balari: Takeda, BMS/Celgene, MSD, Janssen, Amgen, Novartis, Gilead Kite, Sanofi, Roche, Alexion: Honoraria; Takeda, BMS/Celgene, Novartis, Janssen, Gilead, Sanofi: Consultancy; Takeda: Consultancy; Takeda, BMS/Celgene: Other: Research support; Presidency of the GETH-TC, Presidency of the EBMT: Other: Non-profit organisations.

*signifies non-member of ASH