Impact of Ethnicity on Long Term Outcomes of High-Dose Chemotherapy and Upfront Autologous Hematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma

Introduction

Upfront high-dose therapy and autologous hematopoietic stem cell transplantation (autoHCT) is considered a standard of care for eligible patients with newly diagnosed MM (NDMM). Historically, Hispanic or African-American patients with multiple myeloma (MM) have been reported to have worse outcomes. In this study, we examined the impact of ethnicity on the outcome of NDMM patients who received upfront autoHCT at our Center with the hypothesis that all ethnic/racial groups will have similar outcomes.

Methods

In this retrospective, single-center, chart review analysis we identified 1962 patients who self-identified themselves as belonging to one of the three ethnic or racial groups: African-American (AA), Hispanic or Latino (H/L), or White (W). Our primary endpoints were progression free survival (PFS) and overall survival (OS). Our secondary endpoints were response rates as defined by the International Myeloma Working Group criteria. High-risk cytogenetics (HRCG) was defined as the presence of t(4;14), t(14;16), del17p, or 1q21 gain or amplification.

Results

Overall, 353, 440 and 1169 patients identified themselves as AA, H/L or W. The median age at transplant was 58, 57, and 63 years in AA, H/L and W patients (p=0.0005). Three-hundred-thirty patients (16.8%) had autoHCT before 2010, while 1632 (83.2%) in or after 2010 (p=0.0005). HRCG was seen in 26.7%, 23.7% and 28.6% of AA, H/L and W patients, respectively (p=0.09). Median serum creatinine at baseline was 1.10, 1.00, and 1.04 in AA, H/L and W patients, respectively (p=0.02). There was no significant difference in R-ISS stage (p=0.30) or HCT-Comorbidity Index score (p=0.27) between the three groups. Overall, 51.2%, 39.1%, and 59.4% AA, H/L and W patients, respectively, received proteasome inhibitor (PI)/immunomodulatory drug (IMiD)-based triplet regimens (p=0.0005). Pre-transplant response of >CR was seen in 15%, 18.6% and 12.7% of AA, H/L and W patients, respectively. Melphalan alone was used as conditioning in 79%, 80%, and 80.2% AA, H/L and W patients, respectively. Lenalidomide, with or without dexamethasone, was used as maintenance in 83%, 74.2%, and 73.5% of AA, H/L and W patients, respectively.

At the final best response evaluation, 58.9%, 54.1% and 60.1% of AA, H/L and W patients achieved a complete response (CR), while 90.3%, 80.5% and 88.8% of AA, H/L and W patients achieved at least a very good partial response (VGPR). Median progression-free survival (PFS) was 4.4, 3.2, and 5.1 years in AA, H/L and W patients, respectively (p<0.0001). Similarly, median overall survival (OS) was 16.1 years, 8.6 years and 13.6 years in AA, H/L and W patients, respectively (p <0.0001).

We evaluated the impact of several baseline covariates on the PFS and OS. We found that standard-risk CG (p<0.0001) and achieving a CR before autoHCT (p<0.0001) were associated with a better PFS. Similarly, standard-risk CG, serum creatinine <1.5 mg/dL, and the use of PI/IMiD triplets as induction were associated with a better OS.

Conclusion

In this single-center, retrospective analysis, patients who identified themselves as Hispanic/Latino had significantly worse PFS and OS compared to other ethnic groups. That may be related to a smaller proportion of these patients (<40%) receiving a PI/IMiD-based triplet induction and a suboptimal best post-transplant response with only 80% achieving a VGPR.

Bashir:GSK PLC: Research Funding; Stemline Therapeutics, Inc.: Research Funding; Pfizer, Inc.: Research Funding. Srour:Orca Bio: Research Funding; Hansa Biopharma: Consultancy. Lee:Pfizer: Consultancy; Janssen: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Allogene: Consultancy; Takeda: Consultancy, Research Funding; Amgen: Research Funding; Regeneron: Consultancy, Research Funding; Abbvie: Consultancy; Bristol Myers Squibb: Consultancy, Research Funding; Sanofi: Consultancy. Patel:Kite, A Gilead company: Consultancy, Other: scientific advisory board; Poseida: Consultancy; Genentech: Consultancy; Johnson & Johnson (Janssen): Consultancy; BMS: Consultancy, Other: chair of scientific advisory board ; Pfizer: Consultancy; Takeda: Consultancy; Caribou Sciences: Consultancy; Sanofi: Consultancy; Merck: Consultancy; AstraZeneca: Consultancy; Abbvie: Consultancy; Oricel: Consultancy, Other: Chair of scientific board. Kebriaei:Jazz Pharmaceuticals: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Gaballa:Boxer Capital, LLC: Consultancy; GLG: Consultancy; Guidepoint: Consultancy; Bristol Myers Squibb: Consultancy. Thomas:Acerta Pharma: Research Funding; Bristol Myers Squibb: Research Funding; Abbvie: Consultancy, Research Funding; Ascentage Pharma: Research Funding; Sanofi: Research Funding; Mustang Bio: Consultancy, Honoraria; Cellectar Biosciences: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; X4 Pharma: Research Funding; University of Texas MD Anderson Cancer Center: Current Employment; Janssen: Research Funding. Ye:Abbvie: Research Funding; Bristol Myers Squibb: Research Funding; Glaxo Smith Kline: Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Menarini: Research Funding; Regeneron: Research Funding; Sanofi: Consultancy, Honoraria. Orlowski:DEM BioPharma, Inc., Karyopharm Therapeutics, Lytica Therapeutics, Meridian Therapeutics, Monte Rosa Therapeutics, Myeloma 360, Nanjing IASO Biotherapeutics, Neoleukin Corporation, Oncopeptides AB, Pfizer, Inc., Regeneron Pharmaceuticals, Inc., Sporos Bio: Membership on an entity's Board of Directors or advisory committees; BioTheryX: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; AbbVie Inc, Adaptive Biotechnologies Corporation, Asylia Therapeutics Inc, BioTheryX Inc, Bristol Myers Squibb, Karyopharm Therapeutics, Meridian Therapeutics, Monte Rosa Therapeutics, Nanjing IASO Biotherapeutics, Neoleukin Therapeutics, Oncopeptides, Pf: Membership on an entity's Board of Directors or advisory committees; Sanofi, Takeda Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb, CARsgen Therapeutics, Exelixis Inc, Heidelberg Pharma, Janssen Biotech Inc, Sanofi, Takeda Pharmaceuticals USA Inc; Laboratory Research Funding: Asylia Therapeutics Inc, BioTheryX Inc, Heidelberg Pharma: Research Funding; Asylia Therapeutics Inc.: Current equity holder in private company, Patents & Royalties. Shpall:National Marrow Donor Program: Other: Board of Directors/Management; FibroBiologics: Other: Scientific Advisor; Adaptimmune Limited: Other: Scientific Advisor; Zelluna Immunotherapy: Other: Scientific Advisor; Axio Research: Current Employment, Other: Scientific Advisor. Qazilbash:BioLineRx: Research Funding; Angiocrine Bioscience: Research Funding; NexImmune: Research Funding; Janssen Pharmaceuticals: Research Funding; Amgen: Research Funding.