Abstract
Background: T cell receptor-engineered T cell (TCR-T) therapy has shown promising efficacy in advanced solid tumours. Lymphodepleting (LD) chemotherapy improves TCR-T cell therapy efficacy but is associated with significant toxicities. Evidence is sparse regarding the optimum LD regimen for TCR-T cell therapy in solid tumours.
Methods: A systematic review was conducted of interventional, prospective clinical trials describing LD practices prior to TCR-T cell therapy in patients with advanced solid tumours. The objective was to define LD regimens administered prior to TCR-T cell therapy and their effects on specific safety and efficacy outcomes in this patient population.
Results: Searches returned 484 studies, 19 (231 patients) met the eligibility criteria. Cyclophosphamide (cyclo) 60 mg/kg daily (2 days), plus fludarabine (fludara) 25 mg/m2 daily (5 days) was the most common LD regimen (38% of studies). Higher dose LD regimens were associated with increased pooled incidence rates of febrile neutropaenia compared to low dose (0.64, [95% Confidence interval (CI):0.50-0.78], vs. 0.39 [95% CI:0.25-0.53], respectively) but were not significantly associated with higher objective responses (odds ratio: 1.05, 95%CI: 0.60-1.82, p= 0.86). A major shortfall in safety data reporting was identified; determination of LD regimen effects on many safety outcomes was not possible.
Conclusion: Standard consensus guidelines for the design and reporting of adoptive cell therapy (ACT) studies would facilitate accurate risk-benefit analysis for optimising LD regimens in patients with advanced solid tumours.
Methods: A systematic review was conducted of interventional, prospective clinical trials describing LD practices prior to TCR-T cell therapy in patients with advanced solid tumours. The objective was to define LD regimens administered prior to TCR-T cell therapy and their effects on specific safety and efficacy outcomes in this patient population.
Results: Searches returned 484 studies, 19 (231 patients) met the eligibility criteria. Cyclophosphamide (cyclo) 60 mg/kg daily (2 days), plus fludarabine (fludara) 25 mg/m2 daily (5 days) was the most common LD regimen (38% of studies). Higher dose LD regimens were associated with increased pooled incidence rates of febrile neutropaenia compared to low dose (0.64, [95% Confidence interval (CI):0.50-0.78], vs. 0.39 [95% CI:0.25-0.53], respectively) but were not significantly associated with higher objective responses (odds ratio: 1.05, 95%CI: 0.60-1.82, p= 0.86). A major shortfall in safety data reporting was identified; determination of LD regimen effects on many safety outcomes was not possible.
Conclusion: Standard consensus guidelines for the design and reporting of adoptive cell therapy (ACT) studies would facilitate accurate risk-benefit analysis for optimising LD regimens in patients with advanced solid tumours.
| Original language | English |
|---|---|
| Journal | Cancer Immunology, Immunotherapy |
| Publication status | Accepted/In press - 24 Aug 2022 |
Research Beacons, Institutes and Platforms
- Manchester Cancer Research Centre
