Dr Al Malki on the Potential Use of TSC-100 and TSC-101 After Transplant in AML, ALL, and MDS

“We are trying to address a pitfall for some [patients] with hypoidentical donors. We want to reduce the chances of relapse and improve the chances of success [following] transplant. If [data from the Alloha trial] pans out to be positive, this should improve people's survival [post] transplant.”

Monzr M. Al Malki, MD, hematologist/oncologist, associate professor, Divison of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation; director, Unrelated Donor BMT Program; director, Haploidentical Transplant Program, City of Hope, discusses preliminary findings from the phase 1 Alloha trial (NCT05473910), evaluating TSC-100 and TSC-101 as adjuvant TCR-T cell therapies for patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), or myelodysplastic syndromes (MDS) undergoing allogeneic hematopoietic stem cell transplantation (HSCT) with reduced intensity conditioning (RIC).

TSC-100 and TSC-101 are donor-derived T-cell receptor engineered T-cells designed to selectively eliminate residual disease cells post-transplant by targeting HA-1 and HA-2 antigens,

Alloha is exploring the potential of these agents to reduce relapse rates and improve relapse-free survival (RFS) in this high-risk population.

Early findings from the study showed that 8% (2/26) of patients in the treatment arm experienced disease relapse compared with 33% (4/12) with transplant alone. Additionally, event-free survival (EFS) strongly favored the treatment arm, (HR = 0.30). The median time to relapse was not evaluable in the TSC-treated arm, compared with 160 days in the control group. Additionally, TSC-100 and TSC-101 TCR-T cells demonstrated durability, with detectable levels persisting beyond 1-year post-infusion and showing a clear dose-persistence relationship.

The therapies were well-tolerated, with no dose-limiting toxicities or unexpected adverse effects (AEs) reported. The safety profiles for TSC-100 and TSC-101 were consistent with that observed with HSCT alone, supporting the feasibility of incorporating these therapies into the post-transplant care regimen for patients undergoing RIC HSCT. The most common adverse effects of special interest included acute graft-vs-host disease (GvHD), which occurred in 50% of patients in both treatment groups compared with 33% in the control group.

Grade 3/4 acute GvHD was reported in 17% of patients in the control arm and 8% in the TSC-101 arm. No grade 3/4 AEs were observed with TSC-100. Cytokine release syndrome (CRS) occurred in 40% and 67% of patients treated with TSC-100 and TSC-101, respectively, with all events limited to grade 1-2 severity. No cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported across any groups.

Al Malki states that these findings have the potential to address relapse risk in transplant recipients, particularly those with haploidentical donors. Further evaluation of TSC-100 and TSC-101 is ongoing; additional data are expected to validate these early findings, he concludes.