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2379 Maintenance after Autologous Hematopoietic Cell Transplantation Improves Overall Survival and Progression Free Survival Regardless of Disease Stage at Transplant in Newly Diagnosed Myeloma Patients: A Global, Real-World Analysis from the Worldwide Network for Blood and Marrow Transplantation Global Study

Program: Oral and Poster Abstracts
Session: 907. Outcomes Research: Plasma Cell Disorders: Poster I
Hematology Disease Topics & Pathways:
Adult, Clinical Practice (Health Services and Quality), Plasma Cell Disorders, Diseases, Lymphoid Malignancies, Study Population, Human
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Andrew J. Cowan, MD1, Luuk Gras2*, Hiroyuki Takamatsu, MD, PhD3,4, Linda Koster5*, Laurien Baaij III6*, Nada Hamad, MBBS, MSc, BSc7, Anita D'Souza, MD8, Noel Estrada-Merly, MS9*, Parameswaran N. Hari, MD, MBBS10, Wael Saber, MD, MS11, Minako Iida, MD, PhD12*, Shinichiro Okamoto13*, 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, Brig Qamar Un N Chaudhry, MBBS, FCPS24*, Rozan Alfar, MBBS25*, 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 Wang, MD34*, Meng Lv, MD, PhD35, Daniel Neumann36*, Mickey Boon Chai Koh, MD, PhD37*, John Snowden, MD38*, Stefan Schonland39*, Donal P McLornan, MD, PhD40*, Patrick John Hayden, MD41, Rafael De La Camara, MD42, Raffaella Greco, MD43*, Fabio Ciceri, MD44*, Mette D. Hazenberg, MD, PhD45*, Anna Sureda Balari, MD, PhD46, Damiano Rondelli, MD47*, Hildegard T. Greinix, MD48, Mahmoud Aljurf49*, Yoshiko Atsuta50*, Dietger W. Niederwieser, MD51 and Laurent Garderet52*

1Fred Hutchinson Cancer Center, Seattle, WA
2EBMT, Leiden, Netherlands
3Department of Hematology, Kanazawa University, Kanazawa, Japan
4Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA
5EBMT Leiden Study Unit, Leiden, Netherlands
6EBMT Leiden Study Unit, Leiden, the Netherlands;, Leiden, Netherlands
7St Vincent's Hospital, Sydney, NSW, Australia
8Center for International Blood and Marrow Transplant Research, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
9BMT and Cellular Therapy Program, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
10The Medical College of Wisconsin, Brookfield, WI
11Center for International Blood and Marrow Transplant Research, Medical College of Wisconsin, Milwaukee, WI
12Aichi Medical University School of Medicine, Nagakute-cho, Aichi, JPN
13Keio University School of Medicine, Tokyo, JPN
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
24Pathwel center of Hematology and BMT, Rawalpindi, PAK
25Princess Margaret Hospital, Toronto, ON, CAN
26EHU, Oran, Algeria
27Pierre and Marie Curie Center, Algiers, Algeria
28Hospital 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 People’s Hospital, Peking University Institute of Hematology, Beijing, CHN
35Peking University People's Hospital, Beijing, China
36Leipzig University, Leipzig, DEU
37St George's University Hospitals, London, United Kingdom
38Sheffield Blood & Marrow Transplant and Cellular Therapy Programme, 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
41Department of Haematology, Trinity College Dublin, St. James’s Hospital, Dublin, Ireland
42Hospital Universitario de la Princesa, Madrid, Spain
43Unit of Hematology and Stem Cell Transplantation, IRCCS San Raffaele Scientific Institute, Milan, Italy
44Hematology and Bone Marrow Transplantation Unit, I.R.C.C.S. San Raffaele Scientific Institute, Milan, Italy
45Department of Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, Netherlands
46Hematology Department, Institut Català d’Oncologia - Hospitalet, IDIBELL, University of Barcelona, Hospitalet de Llobregat, Spain
47Division of Hematology/Oncology, University of Illinois College of Medicine, Chicago, IL
48Division of Hematology, Medical University of Graz, Graz, Austria
49Department of Hematology, Stem Cell Transplantation, and Cellular Therapy, Cancer Center of Excellence, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
50The Japanese Data Center for Hematopoietic Cell Transplantation, Nagakute, Japan
51Universitaetsklinikum Leipzig Aor, Leipzig, Germany
52Hematology, Pitie-Salpetriere Hospital, Greater Paris University Hospitals (AP-HP), Paris, France

Background:

In eligible newly diagnosed myeloma patients, autologous hematopoietic cell transplantation (AHCT) is the standard of care. The most important prognostic factors are response status at the time of AHCT and receipt of maintenance therapy. Len maintenance post AHCT improves progression-free survival (PFS) and overall survival (OS). Using a global registry, we analyzed whether Len or Thal maintenance can overcome a suboptimal hematological response at AHCT.

Methods:

Data were provided by the Worldwide Network for Blood and Marrow Transplantation (WBMT) through the European Society for Blood and Marrow Transplantation (EBMT), the Center for International Blood and Marrow Transplantation (CIBMTR), 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 myeloma patients receiving AHCT between 2013 and 2017 with data available on maintenance treatment. The primary endpoint was OS and secondary endpoints were PFS, Multivariable 6-month landmark analyses were performed using Cox proportional hazards models including a random effect for country. Apart from maintenance post AHCT (Len vs. Thal vs no maintenance) and hematological response at AHCT, models included patient sex, year of AHCT, Karnofsky score at AHCT, myeloma subclassification, conditioning dosage, interval between diagnosis and AHCT, HCT comorbidity index, ISS at diagnosis, and cytogenetic risk score.

Results:

Among the 61,797 patients in the WBMT study, 11% had information on maintenance. Fifty-one percent had Len (3460 pts), 38% other than Len (2640 pts, including 672 with Thal) and 11% none (767 pts). We report characteristics of the 4903 patients with Len, Thal or no maintenance (47.0% EBMT, 33.9% CIBMTR, 10.4% APBMT, 0.9% EMBMT, 4.4% LABMT, 3.4% Canada) and include 4555 of these who were alive at 6 months post-AHCT in the OS and 4334 who additionally were without relapse in the PFS analysis. The median age at AHCT was 60.0 (IQR: 53.7–65.5) years. Response status at AHCT was: complete response (CR) (19%), very good partial response (VGPR) (39%), partial response (PR) (36%), stable disease/minor response (SD/MR) (5%), relapse/progression (Prog) (1%).

Median follow-up after AHCT was 45 months. In univariable analyses, Len and, to a lesser extent, Thal maintenance was associated with improved OS, PFS, lower RI and NRM (all p<0.001) compared to no maintenance. Improvements were observed regardless of disease status at HCT. OS at 3 years for CR, VGPR, PR and SD/MR/Prog patients was 82%, 80%, 81% and 72% in those without maintenance and was 92 (+10)%, 89 (+9)%, 88 (+7)%, 84 (+12)%, respectively for those with Len, (log-rank p<0.001). PFS at 3 years ranged from 61, 54, 45 and 35% without maintenance to 72 (+11)%, 68 (+14)%, 63 (+18)%, 58 (+23)% with Len for CR, VGPR, PR and SD/MR/Prog patients, respectively (log-rank p<0.001).

In the MVA, better response status at AHCT, and Len maintenance were significantly associated with better OS and PFS. The OS and PFS HR (95% CI) comparing no maintenance vs Len were 1.92, (1.52-2.43), p=0.0004 and HR 1.74 (1.51-2.02) p<0.0001, respectively. The OS HR (95% CI) for VGPR, PR, SD/MR and Rel/Prog vs CR at AHCT was 1.07 (0.82-1.40), 1.23 (0.94-1.61), 1.79 (1.18-2.72) and 2.71 (1.55-4.74), respectively, (overall p=0.0003). For PFS, these estimates were 1.12 (0.95-1.32), 1.43 (1.21-1.68), 1.78 (1.37-2.32) and 2.10 (1.40-3.15), respectively (overall p<0.0001). In the MVA for OS, the benefit of Len maintenance decreased with longer time after AHCT (non-proportional hazards p=0.0002). The HR for no maintenance vs. Len decreased from 3.89 (95% CI 2.55-5.93) at 6 months to 1.02 (95% CI 0.67-1.54) at 36 months. For PFS, a less strong decrease in the HR over time was observed (p=0.05). The HR comparing no maintenance vs Thal for OS was 1.38 (0.98-1.95) and for PFS was 1.21 (0.98-1.49), p=0.06 and 0.07, respectively.

Conclusions:

In this global study of myeloma patients who underwent upfront AHCT, Len maintenance improved PFS and OS, as shown in other studies. Patients with CR as well as those with suboptimal response at AHCT benefit from Len maintenance. Thal, more broadly available globally than Len, was associated with a lesser non-significant trend towards improvement in OS and PFS compared to no maintenance.

Disclosures: Cowan: Sanofi: Consultancy, Research Funding; Regeneron: Research Funding; IgM biosciences: Research Funding; Nektar: Research Funding; HopeAI: Consultancy, Current holder of stock options in a privately-held company; Adaptive Biotechnologies: Consultancy, Research Funding; Caelum: Research Funding; Juno/Celgene: Research Funding; Harpoon: Research Funding; Abbvie: Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Sebia: Consultancy. Takamatsu: Ono: Honoraria; Sanofi: Honoraria; Bristol-Myers Squibb: Honoraria, Research Funding; Adaptive Biotechnologies: Consultancy; Janssen: Honoraria; SRL: Consultancy. D'Souza: Novartis: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Kedrion: Membership on an entity's Board of Directors or advisory committees; Caelum: Research Funding; Abbvie: Research Funding; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: 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 Therapeutics: Current Employment; Obsidian Biotherapeutics: Ended employment in the past 24 months. Mizuno: Hayashikane Sangyo: Research Funding; Janssen pharmaceutical: Honoraria. Bazarbachi: Amgen: Honoraria; Roche: Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Research Funding; Jansen: Honoraria, Research Funding; Caribou: Honoraria; Biologix: Research Funding. Mian: Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: 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; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria. Snowden: Jazz: Other: Advisory board; Medac: Other: Advisory board; Vertex: Other: Advisory board; Jazz: Speakers Bureau; Janssen: Speakers Bureau; Gilead: Speakers Bureau; BMS: Other: Advisory board; Kiadis: Other: IDMC membership for clinical trial. McLornan: Imago Biosciences: Research Funding; Abbvie: Honoraria; Jazz Pharma: Honoraria; Novartis: Honoraria. De La Camara: MSD: Membership on an entity's Board of Directors or advisory committees. Ciceri: ExCellThera: Membership on an entity's Board of Directors or advisory committees. Rondelli: Vertex Pharmaceuticals: Honoraria. Greinix: Sanofi: Honoraria, Speakers Bureau; Stemline: Honoraria, Speakers Bureau; Neovii: Honoraria; Novartis: Honoraria, Speakers Bureau; Gilead: Speakers Bureau; Therakos: Honoraria, Speakers Bureau; BMS: Honoraria. Atsuta: Meiji Seika Pharma Co., Ltd.: Honoraria; Otsuka Pharmaceutical Co., Ltd: Speakers Bureau; CHUGAI PHARMACEUTICAL CO., LTD.: Speakers Bureau; Novartis Pharma KK: Speakers Bureau; Janssen Pharmaceutical K.K.: Honoraria; JCR Pharmaceuticals Co., Ltd.: Consultancy. Garderet: Janssen: Honoraria; BMS: Honoraria; Sanofi: Honoraria.

*signifies non-member of ASH