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2102 Outcomes after Matched Sibling Donor Versus Haploidentical Hematopoietic Cell Transplantation with Post-Transplant Cyclophosphamide-Based GvHD Prophylaxis

Program: Oral and Poster Abstracts
Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment, and Acute Toxicities: Poster I
Hematology Disease Topics & Pathways:
Treatment Considerations, Biological therapies, Biological Processes, Transplantation (Allogeneic and Autologous)
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Muhammad Umair Mushtaq1,2,3, Amir Kasaeian1,3*, Sibgha Gull Chaudhary, MD1,2,3*, Muhammad Kashif Amin, MD1,2,3*, Hediyeh Alemi1,3*, Naghmeh Khavandgar1,3*, Iqra Anwar, MBBS1,3*, Ahmad Basharat, MD1,3*, Matthew McGuirk1,3*, Peiman Hematti, MD3,4, Al-Ola Abdallah, MD1,2,3, Anurag K. Singh, MD1,2,3, Mehdi Hamadani, MD3,5, Joseph P. McGuirk, DO1,2,3 and Moazzam Shahzad, MD3,6

1Division of Hematologic Malignancies & Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS
2US Myeloma Innovations Research Collaborative (USMIRC), Kansas City, KS
3Mikael Rayaan Foundation Global Health Consortium, Kansas City, KS
4Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
5Department of Medicine, Medical College of Wisconsin, Milwaukee, WI
6Department of Oncological Sciences, H. Lee Moffitt Cancer Center, University of South Florida, Tampa, FL

Background: We investigated outcomes and their associated factors after matched sibling donor (MSD) and haploidentical (haplo) allogeneic hematopoietic cell transplantation (allo-HCT) with post-transplant cyclophosphamide (PT-Cy)-based graft-vs-host disease (GVHD) prophylaxis.

Methods: A retrospective multicenter study was conducted, including first allo-HCT recipients in the publicly available Center for International Blood and Marrow Transplant (CIBMTR) registry from 2012 to 2017 (P-5737 dataset, Ustun et al). Outcomes included overall survival (OS), disease-free survival (DFS), relapse, non-relapse mortality (NRM), acute and chronic GVHD, and GVHD-free relapse-free survival (GRFS). Patient- and transplant-related factors were compared using the Chi-square test for categorical variables and the Wilcoxon two-sample test for continuous variables. The median follow-up duration was estimated using the reverse Kaplan-Meier method. Cox proportional hazards regression analyses were performed and hazard ratios (HR) with 95% confidence intervals (CI) were calculated. Variables with p-values <0.2 in univariable analysis and the clinically relevant variables were included in the multivariable models. Statistical analyses were conducted using Stata version 18, and significance was defined as p<0.05.

Results: We included 865 patients with acute myeloid leukemia (AML, 55%), myelodysplastic syndromes (MDS, 26%), and acute lymphoblastic leukemia (ALL, 20%) who received MSD (n=315, 36%) or haplo (n=550, 64%) HCT using PT-Cy-based GVHD prophylaxis. The median recipient age was 57 years, and 59.5% were male. Ethnicity was Caucasians (64%), African Americans (18%), Hispanics (10%), and others (8%). Myeloablative conditioning was performed in 43% of recipients. The graft source was peripheral blood stem cells (PBSC) in 65% of patients. The graft cell dose was >5 million CD34 cells/kg in 40% of patients. The median donor age was 38 years, and 63% were male. The Karnofsky performance status (KPS) was >=90% in 50% of patients, and 51% of the patients had an HCT comorbidity index (HCT-CI) of <3. The median time from diagnosis to transplant was 6.8 months. The median follow-up time was 3.6 years. The median OS, DFS, and GRFS were 2.84 years, 0.99 years, and 0.29 years, respectively. In univariate analyses, MSD, as compared to haplo HCT, was associated with superior OS (HR 0.78, 95% CI 0.64-0.95, p=0.015) and lower NRM (HR 0.72, 95% CI 0.52-0.99, p=0.044), but a lower NRM (HR 0.64, 95% CI 0.43-0.94, p=0.022) was the only significant association in multivariate analyses. In multivariate analyses, significant predictors of outcomes included - OS: age >60 years (HR 1.64, 95% CI 1.12-2.41, p=0.012), HCT-CI >=5 (HR 1.48, 95% CI 1.01-2.16, p=0.043), cytomegalovirus (CMV) donor/recipient negative (HR 0.65, 95% CI 0.47-0.89, p=0.008), graft cell dose >5 million CD34 cells/kg (HR 0.69, 95% CI 0.50-0.95, p=0.021); DFS: age >60 years (HR 1.44, 95% CI 1.02-2.03, p=0.036), HCT-CI >=5 (HR 1.50, 95% CI 1.06-2.13, p=0.023); GRFS: PBSC graft (HR 1.21, 95% CI 1.02-1.43, p= 0.029), donor age >40 years (HR 1.52, 95% CI 1.07-2.15, p=0.018), KPS >=90% (HR 0.78, 95% CI 0.63-0.98, p=0.029), Asians vs. Caucasians (HR 0.66, 95% CI 0.48- 0.91, p=0.011); relapse: HCT-CI >2 (OR 1.56, 95% CI 1.04-2.34, p=0.031) or >5 (OR 1.63, 95% CI 1.06-2.50, p=0.025), reduced-intensity conditioning (HR 1.60, 95% CI 1.01-2.54, p=0.045); NRM: MSD (as above), MDS diagnosis (HR 3.65, 95% CI 1.21-11.00, p=0.022), age >60 years (HR 1.75, 95% CI 1.01-3.01, p=0.044), female-female donor/recipient (HR 0.50, 95% CI 0.28-0.89, p=0.018), time from diagnosis to transplant >1 year (HR 1.93, 95% CI 1.19-3.15, p=0.008), CMV donor/recipient negative (HR 0.48, 95% CI 0.29-0.79, p=0.004); acute GVHD grade II-IV: age >60 years (OR 0.65, 95% CI 0.43-0.99, p=0.044), Asians (OR 0.26, 95% CI 0.12-0.56, p=0.001), growth factor use (HR 1.82, 95% CI 1.17-2.82, p=0.008); and chronic GVHD: PBSC graft (HR 2.34, 95% CI 1.63-3.37, p<0.001), Asians (HR 0.41, 95% CI 0.22-0.77, p=0.06).

Conclusion: In patients who underwent allo-HCT with PT-Cy-based GVHD prophylaxis, a lower NRM was seen with MSD donors, but other outcomes were comparable in MSD vs haplo transplants. We identified several factors associated with post-transplant outcomes, including recipient and donor age, comorbidities and performance status, CMV status, conditioning intensity, and graft source and dose.

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

*signifies non-member of ASH