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3552 Impact of Minimal Residual Disease Status on Outcomes after Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemia

Program: Oral and Poster Abstracts
Session: 723. Allogeneic Transplantation: Long-term Follow-up, Complications, and Disease Recurrence: Poster II
Hematology Disease Topics & Pathways:
Treatment Considerations, Biological therapies, Measurable Residual Disease , Transplantation (Allogeneic and Autologous)
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Moazzam Shahzad, MD1,2, Sohaib Irfan, MD2,3*, Muhammad Kashif Amin, MD2,3,4*, Muhammad Jawad Javed, MBBS2,3, Matthew McGuirk2,3*, Sibgha Gull Chaudhary, MD2,3,4*, Iqra Anwar, MBBS2,3*, Zobia Farooq2,3*, Abdulraheem Yacoub, MD2*, Anurag K. Singh, MD2,3,4, Mehdi Hamadani, MD5, Joseph P. McGuirk, DO2,3,4 and Muhammad Umair Mushtaq2,3,4

1Department of Oncological Sciences, H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL
2Mikael Rayaan Foundation Global Health Consortium, Kansas City, KS
3Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS
4US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, KS
5Department of Medicine, Medical College of Wisconsin, Milwaukee, WI

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a pivotal therapy in curing acute myeloid leukemia (AML). Minimal residual disease (MRD), assessed by multiparameter flow cytometry, aids in predicting post-transplant outcomes. This study aimed to assess how MRD status at the time of transplantation influences post-transplant outcomes in AML patients.

METHODS: Patients diagnosed with acute myeloid leukemia (AML) who underwent allo-HSCT from matched related donors (MRD) or matched unrelated donors (MUD) between 2013 and 2018 were included in this retrospective analysis using the publicly available Center for International Blood and Marrow Transplant Research (CIBMTR) P-5646 dataset by Ramanathan et al. The study utilized data to compare and evaluate patient characteristics and post-transplant outcomes based on pre-allo-HSCT MRD status. Specifically, the study assessed outcomes such as overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD), and chronic graft-versus-host disease (cGVHD), and engraftment. The hazard ratios (HR) with 95% confidence intervals (CI) were calculated using multivariate Cox regression analyses for OS, DFS, relapse, NRM, aGVHD, cGVHD, and platelet and neutrophil engraftment. The multivariate analyses were adjusted for significant variables identified in the univariate analysis. Statistical analysis was conducted using R version 4.16, with statistical significance defined as p <0.05.

RESULTS: We included 3,116 patients with AML undergoing allo-HSCT, among whom 471 tested MRD-positive and 2,645 tested MRD-negative before transplant. The baseline characteristics, including age, gender, ethnicity, race, comorbidity index, performance status, donor/recipient match (human leukocyte antigen, cytomegalovirus, and gender), graft type, conditioning regimen, and GVHD prophylaxis were similar between the two groups. In the MRD-positive group, 59% had a Karnofsky performance status ≥90% compared to 51% in the MRD-negative group (p=0.004). Myeloablative conditioning was used in 66% of the MRD-positive group compared to 55% in the MRD-negative group (p<0.001). In the multivariate regression analyses, MRD-positive status pre-allo-HSCT independently predicted poor OS (41% vs 59%; HR 1.83, 95% CI 1.60-2.09, p<0.001), poor DFS (29% vs 47%; HR 1.94, 95% CI 1.71-2.19, p<0.001), and higher relapse rates (57% vs 37%; HR 2.21, HR 1.92-2.53, p<0.001). Slightly higher rates of grade 2-4 aGVHD (HR 1.18, 95% CI 1.01-1.38, p=0.036) and cGVHD (HR 1.29, 95% CI 1.01-1.41, p=0.043) and slower platelet engraftment (HR 0.73, 95% CI 0.66-0.82, p<0.001) were noted in the MRD-positive group. Neutrophil engraftment (p=0.269) and NRM (p=0.685) did not significantly differ between the two groups. The outcomes analyses were adjusted for conditioning regimen and other significant predictors.

CONCLUSION: The study's findings underscore the potential benefits of eradicating MRD before allo-HSCT. Pre-transplant MRD status is predictive of post-allo-HSCT outcomes, with MRD positivity correlating with decreased overall and disease-free survival and a higher incidence of relapse regardless of conditioning regimen intensity. Strategies to eradicate MRD before allo-HSCT may improve outcomes in AML patients undergoing allogeneic transplantation.

Disclosures: Yacoub: CTI Pharma: Consultancy; PharmaEssentia: Consultancy; Pfizer: Consultancy; Apellis: Consultancy; BMS: Consultancy; Acceleron: Consultancy; Incyte: Consultancy; Gilead: Consultancy; Notable Labs: Consultancy; AbbVie: Consultancy; Novartis: Consultancy; Servier: Consultancy; Celgene: Consultancy. Hamadani: Takeda: Research Funding; CRISPR: Speakers Bureau; DMC, Inc: Speakers Bureau; Genentech: Speakers Bureau; Myeloid Therapeutics: Speakers Bureau; Astellas Pharma: Research Funding; Autolus: Consultancy; Forte Biosciences: Consultancy; AbbVie: Consultancy; CRISPR: Consultancy; Kite Pharma: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Omeros: Consultancy; Spectrum Pharmaceuticals: Research Funding; BeiGene: Speakers Bureau; Genmab: Consultancy; Caribou: Consultancy; ADC Therapeutics: Consultancy, Research Funding, Speakers Bureau; Allovir: Consultancy; Byondis: Consultancy; Sanofi Genzyme: Speakers Bureau; BMS: Consultancy. McGuirk: Allo Vir: Consultancy; CRISPR therapeutics: Consultancy; Caribou bio: Consultancy; NEKTAR therapeutics: Consultancy; Autolus: Consultancy; Envision: Consultancy; Novartis: Consultancy; Kite: Consultancy; BMS: Consultancy; Sana technologies: Consultancy; Legend biotech: Consultancy. Mushtaq: Iovance Biotherapeutics: Research Funding.

*signifies non-member of ASH