Novel T-Cell Therapy Trial Aims to Reduce Post-Transplant Relapse in Blood Cancer Patients

Key Insights

• The ALLOHA phase 1 trial is evaluating engineered T-cell therapies TSC-100 and TSC-101 to address high relapse rates in patients undergoing haploidentical stem cell transplantation.
• Current reduced-intensity conditioning regimens, while expanding transplant accessibility, face challenges with 40-50% relapse rates due to incomplete elimination of malignant cells.
• The trial employs a precision medicine approach using HLA-based stratification to determine patient eligibility for the investigational T-cell therapies, targeting improved post-transplant outcomes.

City of Hope researchers are spearheading an innovative clinical trial aimed at reducing relapse risks in blood cancer patients undergoing haploidentical hematopoietic stem cell transplantation (haplo-HSCT). The phase 1 ALLOHA trial represents a significant step forward in addressing one of the most pressing challenges in transplant medicine.

The trial focuses on patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and myelodysplastic syndromes (MDS) who undergo haplo-HSCT with reduced-intensity conditioning. While this conditioning approach has broadened access to transplantation for older and medically unfit patients, it comes with a substantial drawback: relapse rates of 40-50% due to incomplete elimination of malignant cells.

Novel T-Cell Therapeutic Approach

The ALLOHA trial introduces a precision medicine strategy utilizing engineered T-cell therapies TSC-100 and TSC-101. Dr. Monzr M. Al Malki, director of the Haploidentical Transplant Program at City of Hope, explains the trial's unique design: "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."

Strategic Patient Selection

Patient eligibility for the investigational therapies is determined through careful HLA-based stratification. This targeted approach represents a significant advancement in post-transplant care, as it allows for more precise intervention in patients who face higher relapse risks.

Addressing Critical Unmet Needs

The significance of this trial becomes clear when considering that post-transplant relapse remains the leading cause of mortality in haplo-HSCT recipients. The study's design acknowledges both the curative potential of allogeneic HSCT and the limitations of current reduced-intensity conditioning strategies.

Future Implications

The research team will continue to evaluate how HLA-based stratification affects long-term outcomes with T-cell therapy following haplo-HSCT. This study could potentially establish a new standard for post-transplant care, particularly in managing relapse risk for vulnerable patient populations.