Session: 721. Allogeneic Transplantation: Conditioning Regimens, Engraftment and Acute Toxicities: Poster II
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Biological, Adults, Non-Biological, Clinical Research, Chemotherapy, Clinically Relevant, Diseases, Therapies, Registries, Lymphoid Malignancies, Radiation Therapy, Study Population, Transplantation, Clinical Practice (e.g. Guidelines, Health Outcomes and Services, and Survivorship, Value; etc.)
PATIENTS AND METHODS: Included in the analysis were 2255 patients aged 18-65 years, treated with allo-HCT from either a matched sibling (43%) or unrelated (57%) donor in CR1 (83%) or CR2 (17%), between the years 2010-2020. Patients with Ph(-) B-ALL, Ph(+) B-ALL, and T-ALL were represented in equal proportions. TBI 12Gy + Cy was used in 2105 cases while TBI 12Gy + Flu was administered to 150 patients. Patients treated with TBI/Flu were significantly older (median 35 years vs. 33 years, p=0.006), with poorer Karnofsky performance score (<90, 27% vs. 20%, p=0.03), more frequently transplanted from unrelated donors (71% vs. 57%, p=0.0007) with less frequently use of bone marrow as a source of stem cells (5% vs. 21%, p<0.0001), and in more recent year (median 2018 vs. 2015, p<0.0001).
RESULTS: Engraftment rate was 99% for both TBI/Cy and TBI/Flu patients. In a univariate analysis the use of TBI/Cy as compared to TBI/Flu was associated with a tendency to reduced incidence of relapse (24% vs. 29% at 2 years, p=0.1), increased incidence of grade 2-4 acute graft versus host disease (GVHD, 35.5% vs. 28%, p=0.08) and improved leukemia-free survival (LFS, 62% vs. 57%, p=0.18). The rates and causes of non-relapse mortality (NRM) did not differ significantly between the two conditioning groups. In a multivariate model adjusted for other prognostic factors, TBI/Cy conditioning was associated with reduced risk of relapse (HR=0.69, p=0.049) and increased risk of grade 2-4 acute GVHD (HR=1.57, p=0.03) without significant effect on other transplantation outcomes.
An additional analysis was performed with TBI/Cy treated patients (n=132) matched strictly to those treated with TBI/Flu (n=132) in terms of disease subtype, disease status and donor type with the nearest neighbor for patient age, patient and donor sex, in vivo T-cell depletion, Karnofsky score and source of stem cells; the use of TBI/Cy as compared to TBI/Flu was associated with significantly reduced rate of relapse (18% vs. 30% at 2 years, p=0.015) and a tendency to an improved LFS (65% vs. 59%, p=0.07) and overall survival (OS, 73% vs. 68%, p=0.16) without effect on NRM and GVHD.
CONCLUSIONS: The use of myeloablative TBI/CY as conditioning prior to allo-HCT for adult patients with ALL in CR1 or CR2 is associated with stronger anti-leukemic effect leading to significantly lower relapse rate compared to TBI/Flu and therefore should be likely considered a preferable regimen.
Disclosures: Giebel: Janssen: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Labopin: Jazz Pharmaceuticals: Honoraria. Socie: Alexion: Research Funding. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Kröger: Novartis: Research Funding; Riemser: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Gilead/Kite: Honoraria; Celgene: Honoraria, Research Funding; AOP Pharma: Honoraria. Forcade: Novartis: Consultancy, Other: Travel Support, Speakers Bureau; Gilead: Other: Travel Support, Speakers Bureau; Jazz: Other: Travel Support, Speakers Bureau; MSD: Other: Travel Support. Huynh: Jazz Pharmaceuticals: Honoraria. Spyridonidis: Menarini: Current Employment. Perić: therakos: Honoraria; servier: Honoraria; MSD: Honoraria; Astellas: Honoraria; NOVARTIS: Honoraria; Abbvie: Honoraria; Pfizer: Honoraria. Mohty: Pfizer: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Astellas: Honoraria; Gilead: Honoraria; Jazz: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria; Bristol Myers Squibb: Honoraria; Takeda: Honoraria; Sanofi: Honoraria, Research Funding; Adaptive Biotechnologies: Honoraria.