Dr Al Malki on Reducing Relapse Risk in Patients with MDS Undergoing Haplo-HSCT

“The study is designed as a phase 1 study, having a treatment arm and a control arm. [Patients] get randomly assigned biologically based on the status of HLA-1 or HLA-2, [and these patients] can receive the treatment; their donors should be HLA-1 or HLA-2 negative.”

Monzr M. Al Malki, MD, hematologist/oncologist, associate professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation; director, Unrelated Donor BMT Program; and director, Haploidentical Transplant Program, City of Hope, discusses the rationale for the ongoing phase 1 ALLOHA trial (NCT05473910) and its approach to using treatment with TSC-100 and TSC-101 to reduce relapse risk in patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS).

Al Malki notes that haplo-HSCT with reduced-intensity conditioning has expanded transplant eligibility, particularly for older and medically unfit patients, Al Malki explains. However, reduced-intensity conditioning regimens are associated with a 40% to 50% relapse rate due to lower-intensity chemotherapy failing to eradicate all malignant cells, he says. The ALLOHA trial seeks to address this challenge through biologically driven randomization to receive the engineered T-cell therapies TSC-100 and TSC-101 based on HLA-1 and HLA-2 status, allowing for targeted intervention in patients at higher risk of relapse.

In this phase 1 study, patients enrolled to the investigational arm are stratified based on HLA-1 and HLA-2 expression, Al Malki states. Patients with HLA-1 or HLA-2 expression are eligible to receive the investigational therapies, and their donors must be negative for both markers. The study is evaluating whether this T-cell therapeutic approach can enhance post-transplant immune responses and reduce relapse rates.

The study’s design reflects the curative potential of allogeneic HSCT and acknowledges the limitations of current reduced-intensity conditioning strategies, Al Malki adds, given that post-transplant relapse remains the leading cause of mortality in this setting. The ALLOHA trial’s biologically driven randomization introduces a precision-medicine approach to post-transplant disease control.

Going forward, Al Malki and colleagues will continue this study further assess the clinical effects of HLA-based stratification on long-term outcomes with T-cell therapy following haplo-HSCT, he concludes.