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4962 Trends in Outcomes over Three Decades after Upfront Autologous Stem Cell Transplant for Multiple Myeloma at MD Anderson Cancer Center

Program: Oral and Poster Abstracts
Session: 731. Autologous Transplantation: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Biological therapies, Plasma Cell Disorders, Diseases, Therapies, Lymphoid Malignancies, Transplantation
Monday, December 11, 2023, 6:00 PM-8:00 PM

Oren Pasvolsky, MD1,2,3*, Curtis Marcoux, MD, MSc4*, Jianliang Dai, MS5*, Denái R. Milton, MS5*, Mark R. Tanner, PhD1*, Naureen Syed, MD1*, Qaiser Bashir, MD1, Samer A. Srour, MD1, Neeraj Y. Saini, MD1, Paul Lin, MD, PhD1, Jeremy Ramdial, MD1, Yago Nieto, MD, PhD1, Hans Lee, MD6, Krina K. Patel, MD, MSc6, Elisabet E. Manasanch, MD6, Partow Kebriaei, MD1, Sheeba K. Thomas, MD6, Donna M. Weber, MD6, Robert Z. Orlowski, MD, PhD7, Elizabeth J. Shpall, MD1, Richard E. Champlin, MD1 and Muzaffar H. Qazilbash, MD1

1Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
2Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikva, Israel
3Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
4Division of Hematology, Dalhousie University, Halifax, Canada
5Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
6Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
7Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX

Introduction

Remarkable advances have been made in the treatment of multiple myeloma (MM) with the advent of novel therapies and the use of post-transplant maintenance. We report trends in outcomes of MM patients who received upfront autologous hematopoietic stem cell transplantation (autoHCT) at our institution over more than three decades.

Methods

We conducted a single-center retrospective study of patients with newly diagnosed MM undergoing upfront autoHCT between 1988 to 2021. Patients were grouped by the year of autoHCT: 1988–2000 (n=249), 2001–2005 (n=373), 2006–2010 (n=568), 2011–2015 (n=815) and 2016–2021 (n=1036). High-risk cytogenetic abnormalities were defined as del17p, t(4;14), t(14;16), 1q21 gain or amplification by fluorescence in situ hybridization. Progression free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and group differences were assessed using the log-rank test. Associations between demographic and clinical factors and survival outcomes were evaluated using Cox proportional hazards regression analysis.

Results

A total of 3041 patients were included in our analysis. Median age at autoHCT increased from 52 years (1988-2000) to 62 years (2016-2021), with only 1% of transplanted patients being ≥ 65 years of age in 1988-2000, compared to 38% in 2016-2021 (p<0.001). The proportion of African-American patients increased from 9% in 1988-2000 to 19% in 2016-2021 (p=0.004). The incidence of high-risk cytogenetics increased from 15% in 1988-2000 to 40% in 2016-2021 (p<0.001). The comorbidity burden, as measured by the hematopoietic cell transplantation-specific comorbidity index (HCT-CI), increased over time, with 17% of patients having HCT-CI>3 in 1988-2000 compared to 28% in 2016-2021 (p<0.001). Induction regimens evolved over time from predominately conventional chemotherapy (39%) in 1988-2000 to immunomodulatory drug (IMiD) and proteasome inhibitor (PI)-based regimens, with 74% receiving an IMiD-PI containing triplet [39% bortezomib, lenalidomide and dexamethasone (VRD) and 35% carfilzomib, lenalidomide and dexamethasone (KRD)] between 2016-2021 (p<0.001). Maintenance therapy was used in >80% from 2011 onwards (Table 1).

Response rates prior to autoHCT steadily improved with 4% and 10% patients achieving ≥CR and ≥VGPR between 1988-2000, compared to 19% and 65% between 2016-2021, respectively. At day 100 post-transplant, 24% and 49% patients achieved ≥CR and ≥VGPR between 1988-2000 compared to 41% and 81% between 2016-2021, respectively. At best post-transplant response, 33% and 53% patients achieved ≥CR and ≥VGPR between 1988-2000 compared to 63% and 91% between 2016-2021, respectively.

The median PFS in the entire study population was 38.3 months (95% CI 36.4-40.3), improving from 22.3 months between 1988-2000 to 58.6 months between 2016-2021 (hazard ratio [95% CI]: 0.42 [0.36-0.50], p<0.001; Figure 1A). Notably, patients with high-risk cytogenetics also had an improvement in PFS in recent years, with a median PFS of 28.0 months (0.38 [0.26-0.55], p<0.001) and 36.8 months (0.32 [0.22-0.46], p<0.001) in 2011-2015 and 2016-2021, respectively, compared to only 13.7 months in 2001-2005. Patients aged ≥65 years also had an improvement in median PFS from 33.6 months (95% CI 23.1-44.2) between 2001-2005 to 52.8 months (95% CI 40.0-68.5, p<0.001) between 2016-2021.

Median OS was 99.4 months (95% CI 94.2-104.0) in the entire study population, steadily improving from 55.1 months to not reached (0.41 [0.33-0.52], p<0.001) in 1988-2000 and 2016-2021, respectively (Figure 1B). Similarly, in those with high-risk cytogenetics, OS improved with a median OS of 32.9 months in 2001-2005 compared to 66.5 months (0.39 [0.26-0.61], p<0.001) in 2016-2021. Between 1988-2000, day 100 non-relapse mortality (NRM) was 6%, whereas from 2001 onwards NRM remained ≤ 1% (p<0.001).

Conclusions

This single-center analysis of over 3,000 newly diagnosed MM patients undergoing upfront autoHCT demonstrates significant improvements in the depth of response and survival outcomes over the past three decades, even in patients with high-risk disease. NRM remained <1% despite increasing age and comorbidity burden.

Disclosures: Bashir: Acrotech: Research Funding; Stemline: Research Funding; GSK: Research Funding; Pfizer: Research Funding. Srour: Orca Bio: Research Funding. Saini: GSK: Research Funding; Panbela Theraputics: Research Funding. Lin: Takeda: Patents & Royalties, Research Funding. Nieto: Affimed: Research Funding; Astra Zeneca: Research Funding; Secura Bio: Research Funding. Lee: Janssen: Consultancy, Research Funding; Amgen: Research Funding; Regeneron: Consultancy, Research Funding; Allogene Thereapeutics: Consultancy; Takeda Pharmaceuticals: Consultancy, Research Funding; Monte Rosa Therapeutics: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; GlaxoSmithKline: Consultancy, Research Funding; Genentech: Consultancy; AbbVie: Consultancy; Celgene: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding. Patel: AbbVie; Allogene Therapeutics, Inc.; Arcellx; Bristol Myers Squibb/Celgene Corporation; Cellectis; Janssen Pharmaceuticals, Inc.; Nektar Therapeutic; Poseida Therapeutics; Precision BioSciences, Inc.; and Takeda Pharmaceuticals U.S.A., Inc.: Research Funding; Takeda: Consultancy; AbbVie; Arcellx, AstraZeneca; Bristol Myers Squibb/Celgene Corporation; Caribou Science; Cellectis; Curio Bioscience; Genentech; Janssen Pharmaceuticals, Inc.; Karyopharm; Legend Biotech; Merck & Co., Inc.; Oncopeptides; Pfizer; Precision BioSciences: Consultancy. Manasanch: Sanofi: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Telo Genomics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Adaptive Biotechnologies: Honoraria. Kebriaei: Jazz: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Thomas: Bristol Myers Squibb, Janssen Pharma Genentech, X4 pharma, Cellectar Biosciences, Ascentage Pharma: Research Funding; Genentech: Research Funding; Abbvie, Cellectar Biosciences: Consultancy; X4 pharma: Research Funding; Cellectar Biosciences: Consultancy; Cellectar Biosciences: Research Funding; Janssen Pharma: Research Funding; Ascentage Pharma: Research Funding. Orlowski: Asylia Therapeutics, BioTheryX Inc., Heidelberg Pharma: Other: Laboratory Research Funding, Research Funding; BMS/Celgene Corporation, CARsgen Therapeutics, Exelixis Inc., Heidelberg Pharma, Janssen Biotech Inc., Sanofi/Genzyme, Takeda Pharmaceuticals USA Inc.: Other: Clinical Research Funding, Research Funding; AbbVie, Adaptive Biotech, Asylia Therapeutics, Inc., BioTheryX, Bristol-Myers Squibb Pharmaceuticals, Karyopharm Therapeutics, Meridian Therapeutics, Monte Rosa Therapeutics, Nanjing IASO Biotherapeutics, Neoleukin Corporation, Oncopeptides AB, Pfizer, In: Consultancy, Honoraria; Asylia Therapeutics: Current equity holder in private company, Patents & Royalties. Shpall: Celaid Therapeutics: Membership on an entity's Board of Directors or advisory committees; Navan: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Fibrobiologics: Membership on an entity's Board of Directors or advisory committees; Axio: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: License agreement; Affimed: Other: License agreement; Syena: Other: License agreement; NY Blood Center: Membership on an entity's Board of Directors or advisory committees. Champlin: Johnson & Johnson/Janssen: Consultancy; Omeros: Consultancy; Orca Bio: Consultancy; Arog: Consultancy; Cell Source: Research Funding; Takeda Corporation: Patents & Royalties; Actinium Pharmaceuticals: Consultancy; Kadmon: Consultancy. Qazilbash: Bioline: Other: Advisory board; NexImmune: Research Funding; Angiocrine: Research Funding; Janssen: Research Funding; Amgen: Research Funding.

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