-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

2128 HLA B-Leader Mismatch Is Associated with Poor Outcomes in NIMA/NIPA Mismatched Haploidentical Sibling Donor HCT

Program: Oral and Poster Abstracts
Session: 732. Allogeneic Transplantation: Disease Response and Comparative Treatment Studies: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, Diseases, Lymphoid Malignancies, Myeloid Malignancies
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Rohtesh S. Mehta, MD1, Rima M. Saliba, PhD1*, Amin M Alousi, MD1, Gheath Alatrash, PhD, DO2, Qaiser Bashir, MD1, Chitra Hosing, MD1, Partow Kebriaei, MD1, Issa F. Khouri, MD1, Yago Nieto, MD3, Betul Oran, MD, MS4, Uday R Popat, MD1, Muzaffar H Qazilbash, MD1, Jeremy L. Ramdial, MD1, Gabriela Rondon, MD5, Samer A Srour, MD, MS6, Katy Rezvani, MD1, Richard E Champlin, MD1, Elizabeth J Shpall, MD1 and Kai Cao, MS, MD7

1Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX
2Department of Hematopoietic Biology & Malignancy, The University of Texas MD Anderson Cancer Center, Pearland, TX
3Department of Stem Cell Transplantation and Cellular Therapy, UT M.D. Anderson Cancer Ctr., Houston, TX
4Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas, MD Anderson Cancer Center, Houston, TX
5The University of Texas MD Anderson Cancer Center, Houston, TX
6Stem Cell Transplantation and Cellular Therapy, MD Anderson Cancer Center, Houston, TX
7Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX

Background: Sibling haplo donors can be broadly categorized as non-inherited maternal (NIMA) or paternal (NIPA) antigen mismatched based on the non-shared haplotype with the recipient. Older studies with non-PTCy prophylaxis suggested a benefit of NIMA-mismatched over NIPA-mismatched donors, but the same has not been studied with PTCy prophylaxis, especially in the context of increasing recognition of the impact of specific loci HLA-mismatches in haplo HCT, such as the B-leader, which is a leader peptide that is preferentially bound by HLA-E, the ligand for natural killer (NK) receptor NKG2.

Objective: To compare the outcomes of NIMA-vs NIPA-mismatched haplo sibling donors and specific loci HLA-mismatches in the setting of T-cell replete HCT with PTCy prophylaxis.

Results: We included 57 patients: 29 were NIMA-mismatched and 28 were NIPA-mismatched. Median age at HCT (31 yrs vs 37 yrs, p=0.1) and donor age (32 yrs vs 41 yrs, p=0.1) were similar in both groups. Most received RIC (72% vs 68%, p=0.5), BM graft (79% vs 82%, p=0.8), had HCT-CI >3 (55% vs 54%, p=0.9) and low/intermediate DRI (62% vs 54%, p=0.4) and were ABO matched (65% vs 71%, p=0.8) with the donor. There was a significantly higher proportion of female-donor to male-recipients in the NIMA- than NIPA-mismatched group (55% vs 21%, p=0.005). Specific HLA-mismatches were similar in both groups: B-leader (52% vs 32%, p=0.1), DRB1 (96% each), DQB1 (90% vs 86%, p=0.5), DPB1 (76% vs 79%, p=0.9). The median follow-up was 38 vs 13 months. There were no graft failures, and the median time to engraftment was similar (18 vs 19 days, p=0.3). The cumulative incidence of grade II-IV aGVHD was 31% vs 58%, p=0.04; with no differences in grade III-IV aGVHD (10% vs 11%, p=0.9), cGVHD (11% vs 13%, p=0.9); NRM (28% vs 33%, p=0.9), relapse (21% vs 11%, p=0.4), or OS (54% vs 55%, p=0.8) in NIMA-vs NIPA-mismatched, respectively.

In multivariate analysis, NIMA-mismatch (HR 0.1, 95% CI 0.02-0.6, p=0.01 in females) and HLA-A mismatch (HR 0.2, 95% CI 0.1-0.6, p=0.005) were associated with significantly lower risk of grade II-IV aGVHD, while age at HCT >50 yr was high risk for grade II-IV aGVHD (HR 2.7, 95% CI 1.1-6.9, p=0.04). No factor predicted grade III-IV aGVHD, cGVHD or relapse, likely related to a small number of events. B-leader mismatch was associated with high NRM (HR 3.8, 95% CI 1.04-13, p=0.04), poor PFS (HR 2.7, 95% CI 1.1-6.7, p=0.03), and a trend for lower OS (HR 2.4, 95% CI 0.9-6.3, p=0.06). High/very-high DRI was associated with high NRM (HR 4.4, 95% CI 1.5-13, p=0.008) and poor OS (HR 2.6, 95% CI 1-6.6, p=0.05). HCT-CI >3 (HR 2.9, 95% CI 0.9-8.8, p=0.05) was associated with poor OS. Neither NIMA-mismatch nor any other independent HLA-locus mismatches (except B-leader) had an impact on NRM, relapse, PFS, or OS.

Conclusion: Among sibling haplo donors, a B-leader matched donor should be prioritized whenever possible. When multiple B-leader matched donors are available, considering the sample size limitations, our data suggest that a donor mismatched at A-locus (lower aGVHD) and/or a NIMA-mismatched donor (lower aGVHD in females) could be selected.

Disclosures: Mehta: Syndax: Research Funding; Orca Bio: Research Funding. Alousi: Incyte: Honoraria, Research Funding; Sanofi / Kadmon: Honoraria; Genetech: Consultancy; Mallinkrodt: Honoraria; Prolacta: Consultancy. Kebriaei: Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Ziopharm: Research Funding. Nieto: Astra Zeneca: Research Funding; Affimed: Other: Scientific advisory Board, Research Funding; Secura Bio: Research Funding. Oran: AROG: Research Funding; ASTEX: Research Funding. Popat: Bayer: Research Funding; Incyte: Research Funding; Abbvie: Research Funding; Novartis: Research Funding; Iovance: Consultancy. Srour: Orca Bio: Research Funding. Rezvani: Navan Technologies: Other: Participates on the Scientific Advisory Board ; Bayer: Other: Participates on the Scientific Advisory Board ; GSK: Other: Participates on the Scientific Advisory Board ; Virogin Biotech: Other: Participates on the Scientific Advisory Board ; AvengeBio: Other: Participates on the Scientific Advisory Board ; GemoAb: Other: Participates on the Scientific Advisory Board ; Takeda: Patents & Royalties, Research Funding; Affimed: Research Funding; Caribou Biosciences: Other: Participates on the Scientific Advisory Board . Champlin: Kadmon: Consultancy; Bluebird: Other: Data Safety Monitoring Board; General Oncology: Other: Data Safety Monitoring Board; Omeros: Consultancy; Johnson &Johnson: Consultancy; Actinium: Consultancy; Cell Source Inc.: Research Funding. Shpall: adaptimmune: Consultancy; Takeda: Patents & Royalties; Bayer: Honoraria; Affimed: Other: License agreement; Fibroblasts and FibroBiologics: Consultancy; Navan: Consultancy; NY blood center: Consultancy; axio: Consultancy.

*signifies non-member of ASH