Session: 723. Allogeneic Transplantation: Long-term Follow-up and Disease Recurrence: Poster II
Hematology Disease Topics & Pathways:
Minimal Residual Disease
Methods: We performed a single center retrospective study to test the hypothesis that pre-transplant MRD positivity is associated with outcomes in patients receiving HCT in CR2 or beyond for ALL. MRD was measured by 6-color flow cytometry with a sensitivity of 0.01%. Consecutive pediatric and adult patients who underwent first allogeneic HCT between the years 2004-2021 for ALL in CR2 or beyond were included.
Results: We identified 162 patients (Table 1), 123 (76%) with B-ALL and the remainder with T-ALL. The majority (80%, n=129) of patients were in CR2 at the time of HCT, the remainder in third CR or beyond (CR3+). One hundred and five (65%) patients were male and median age at transplant was 31 (range 4-69) years. Graft source was either matched unrelated donor (MUD) (43%, n=69), matched sibling donor (MSD) (24%, n=39), haploidentical (18%, n=29) or cord blood transplantation (CBT) (15%, n=25). Pre-HCT MRD status was determined for 150 (93%) of patients and of those was positive in 43 (26%). Subsequent analyses were limited to the subset of patients with known MRD status. There was no statistical difference in characteristics according to MRD status except for higher proportion of CR3+ patients (33% vs. 16%, p=0.02) and comorbidity index >2 (70% vs. 40%, p=0.001) in MRD positive vs. negative patients. The median follow-up in surviving patients was 62 (range 20-104) and 47 (range: 2-171) months in MRD positive and negative patients, respectively. In multivariate analysis (MVA) evaluating transplantation outcomes at 3 years, pre-HCT MRD positivity was associated with a higher rate of disease relapse (HR 1.9, 95% CI 1.1-3.6; p=0.02); but it had no impact on non-relapse mortality (NRM) (HR 0.8, 95% CI 0.4-1.8; p=0.6). Subset analyses showed that these trends were consistent for patients receiving HCT in CR2 or CR3+; however the impact on disease relapse was more pronounced for patients in CR2 at HCT. MRD positivity was also associated with less favorable overall (HR 1.96, 95% CI 1.2-3.3; p=0.01) and progression-free survival (PFS) (HR 2.5, 95% CI 1.5-4.2; p<0.001) for patients receiving HCT in CR2. MRD was not associated with OS (HR 0.9, 95% CI 0.4-2, p=0.8) or PFS (HR 0.8, 95% CI 0.3-1.7, p=0.5) for patients receiving HCT in CR3+. As shown in Figure 1 A-B, OS and PFS were significantly superior for MRD negative patients receiving HCT in CR2. OS and PFS for MRD positive patients in CR2 were comparable to patients receiving HCT in CR3+.
Conclusions: Pre-transplant MRD positivity is predictive of disease relapse in patients undergoing HCT for ALL in CR2 or beyond; however, the survival advantage associated with MRD negativity maybe limited to patients undergoing HCT in CR2.
Disclosures: Popat: Bayer: Research Funding; Iovance: Consultancy; Incyte: Research Funding; Abbvie: Research Funding; Novartis: Research Funding. Alousi: Genetech: Consultancy; Incyte: Honoraria, Research Funding; Mallinkrodt: Honoraria; Sanofi / Kadmon: Honoraria; Prolacta: Consultancy. Oran: ASTEX: Research Funding; AROG: Research Funding. Short: Pfizer: Consultancy; Amgen: Consultancy, Honoraria; Novartis: Consultancy; Astellas: Research Funding; Stemline Therapeutics: Research Funding; AstraZeneca: Consultancy; Takeda Oncology: Consultancy, Research Funding. Ravandi: AstraZeneca: Consultancy; Astellas: Consultancy, Honoraria, Research Funding; Astex/Taiho: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; Syos: Consultancy, Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Biomea Fusion, Inc.: Research Funding; Xencor: Research Funding; Prelude: Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Novartis: Consultancy. Champlin: Cell Source Inc.: Research Funding; Bluebird: Other: Data Safety Monitoring Board; Actinium: Consultancy; General Oncology: Other: Data Safety Monitoring Board; Kadmon: Consultancy; Johnson &Johnson: Consultancy; Omeros: Consultancy. Shpall: NY blood center: Consultancy; Bayer: Honoraria; Takeda: Patents & Royalties; Fibroblasts and FibroBiologics: Consultancy; Affimed: Other: License agreement; Navan: Consultancy; adaptimmune: Consultancy; axio: Consultancy. Kebriaei: Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ziopharm: Research Funding; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding.
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