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3529 Haploidentical Transplant Using Selective Ex-vivo TCR-Αβ Depleted and Upfront Memory T-Cell Add-Back Is Associated with Lower Chronic Gvhd and More Favorable Gvhd-Free/Relapse-Free Survival As Compared to Matched Related and Unrelated Donor Transplant for Adults with Hematological Malignancies

Program: Oral and Poster Abstracts
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD and Immune Reconstitution: Poster II
Hematology Disease Topics & Pathways:
Lymphoid Leukemias, ALL, Acute Myeloid Malignancies, AML, MDS, Adult, Lymphomas, MPN, Clinical Practice (Health Services and Quality), CML, B Cell lymphoma, GVHD, T Cell lymphoma, Chronic Myeloid Malignancies, CMML, Diseases, Immune Disorders, Lymphoid Malignancies, Myeloid Malignancies, Study Population, Human
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Victor Ling Wei Teik1*, Yeh Ching Linn2*, Huirong Han1*, Michelle Poon, MBBS, MRCP1*, Lip Kun Tan1*, Joanne Shu Xian Lee1*, Yang Liang Boo, MD, MRCP1*, Ian Wu, MBBS, MRCP, MD1*, Jean Rachel Catapia, MD1*, Aloysius Yew Leng Ho2, William Ying Khee Hwang2, Yeow Tee Goh, MD2, Francesca Lim, MBBS2*, Hein Than, MD, FRCPath, MRCP2, Lawrence Cheng Kiat Ng, MD2*, Jeffrey Kim Siang Quek2*, Tertius Tansloan Tuy, MD, MRCP(UK)2*, Balamurugan Vellayappan3*, Zi Yi Lim, MBBS, FRCP, FRCPath4*, Colin Phipps Diong, MD5*, Yvonne Loh6*, Kheng Wei Yeoh7*, Brian Ho7*, Wen Shen Looi7*, Yin Jie Koh1*, Teck Guan Soh1*, Kee Khiang Heng8*, Gina Gan8*, Wing Leung, PhD, MD9 and Liang Piu Koh1*

1Department of Haematology-Oncology, National University Cancer Institute, Singapore, Singapore
2Department of Haematology, Singapore General Hospital, Singapore, Singapore
3Department of Radiation Oncology, National University Cancer Institute, Singapore, Singapore
4Centre for Clinical Haematology, Mount Elizabeth Novena Hospital, Singapore, Singapore
5Parkway Cancer Centre, Mount Elizabeth Hospital, Singapore, Singapore
6Curie Oncology, Singapore, Singapore
7Division of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore
8Singapore General Hospital, Singapore, Singapore
9KK Women’s and Children’s Hospital, Duke-NUS, Singapore, Singapore

Background

Haploidentical hematopoietic cell transplantation (HCT) with selective T-cell depletion (Haplo-TCD) and memory T-cell add-back has been adopted by our centers with good results. Using propensity score matching, we previously demonstrated that this approach produced better outcomes compared with post-transplant cyclophosphamide approach. [Victor LWT, et al. Blood (2022) 140 (Supplement 1):10500–10501]. Here, we compare the efficacy of Haplo-TCD with conventional donor sources, including matched-related donors (MRD), matched-unrelated donors (MUD), and mismatched unrelated donors (MMUD).

Methods

In this multicenter retrospective analysis, we evaluated the outcomes of 488 adult patients with hematological malignancies who underwent allogeneic HCT between January 2017 and December 2023. Our cohort included patients who received transplants from Haplo-TCD (n=160), MRD (n=160), MUD (n=143) and MMUD (n=25), following either myeloablative (n=182) or reduced-intensity conditioning (n=306) regimen.

Results

Median age of patients at the time of HCT was 52 years old (Range: 17-74). Patients in the MRD group (median age, 48) were younger than those in other groups. The most common diagnoses in all groups were acute myelogenous leukemia and myelodysplastic syndrome.

At a median follow-up of 34 months (Range: 5-90 months), the 3-year overall survival (OS) for Haplo-TCD, MRD, MUD, and MMUD HCT were 71.1%, 67.2%, 58.2%, and 60.6%, respectively (p=0.167). The corresponding 3-year event-free survival (EFS) were 61.9%, 58.1%, 46.5%, and 40.9%, respectively (p=0.019). In univariate analysis, the 3-year cumulative incidence (CI) relapse rate differed significantly between Haplo-TCD (20.2%) vs MUD (35.7%) (p=0.009) as well as vs MMUD (42.6%) (p=0.007) but was not statistically significant when compared to MRD (26.2%) (p=0.353). There was no statistically significant difference in CI of non-relapse mortality (NRM) at 3 years across all groups: Haplo-TCD 16.2%, MRD 15.7%, MUD 17.8%, and MMUD 16.5% (p=0.973).

The difference in CI of grade 2-4 acute GVHD (aGVHD) at day 180 was not statistically significant among the groups. However, CI of grade 3-4 aGVHD differed significantly (Haplo-TCD 6.9% vs MRD 14.4% vs MUD 4.9% vs MMUD 16.2%; p=0.0155). Remarkably, the 3-year chronic GVHD (cGVHD) incidence was the lowest in Haplo-TCD group (Haplo-TCD 8.1% vs MRD 56.3% vs MUD 27.6% vs MMUD 20.0%; p<0.001). Differences in relapse and cGVHD have resulted in the most favorable 3-year GVHD-free/Relapse-free survival (GRFS) in Haplo-TCD group (Haplo-TCD 54.4% vs MRD 10.9% vs MUD 26.5% vs MMUD 18.0%; p<0.001).

Patients with higher HCT comorbidity index (HCT-CI) ≥1 (p<0.001), high/very high disease risk index (p<0.001) and CMV seropositive status (p=0.003) were shown to have worse OS and EFS in multivariate analysis. Notably, Haplo-TCD was associated with significantly more favorable outcomes in EFS (p=0.03), cGVHD (p<0.001) and GRFS (p<0.001).

For patients with low/intermediate risk DRI, the 3-year OS were 80.3% for Haplo-TCD, 75.6% for MRD, 61.3% for MUD, and 79.0% for MMUD (p=0.026), with corresponding 3-year EFS of 72.8%, 66.6%, 51.0%, and 55.4% (p=0.069), and 3-year GRFS of 63.0%, 13.9%, 28.7%, and 30.0% (p<0.001). In patients with high/very high risk DRI, the 3-year OS were 53.3% for Haplo-TCD, 46.3% for MRD, 50.0% for MUD, and 33.3% for MMUD (p=0.66), with corresponding 3-year EFS of 45.5%, 36.8%, 23.1%, and 20.0% (p=0.078), and 3-year GRFS of 37.9%, 3.4%, 19.0%, and 0% (p<0.001).

Conclusions

Although non-randomized, our findings provide strong evidence that Haplo-TCD results in outcomes equivalent to those achieved with MRD and more favorable than those with MUD, particularly in terms of cGVHD and GRFS. This approach offers an additional alternative for patients lacking HLA-matched donors, while also obviating the cost and time associated with searching for unrelated donors.

Disclosures: Goh: Novartis: Consultancy; AstraZeneca: Consultancy; Johnson & Johnson: Consultancy, Honoraria; Antengene: Consultancy; Amgen: Consultancy; EUSA Pharma: Consultancy; Pfizer: Consultancy; MSD: Honoraria; Roche: Honoraria; Astellas: Honoraria; AbbVie: Honoraria; NS Pharma: Consultancy. Than: AbbVie: Consultancy, Honoraria, Other: Advisory fees; GSK: Consultancy, Honoraria, Other: Advisory fees; BMS: Consultancy, Honoraria, Other: Advisory fees; PharmaEssentia Corporation: Consultancy, Honoraria, Other: Advisory fees; Novartis: Consultancy, Honoraria, Other: Advisory fees.

*signifies non-member of ASH