Journal
CANCER IMMUNOLOGY IMMUNOTHERAPY
Volume 72, Issue 4, Pages 805-814Publisher
SPRINGER
DOI: 10.1007/s00262-022-03287-1
Keywords
TCR-T cell; Solid tumours; Lymphodepletion; Conditioning chemotherapy; Safety; Efficacy
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Background TCR-T therapy has shown promise in solid tumors, but there is limited evidence on the optimal LD regimen. This systematic review analyzed 19 clinical trials and found that cyclophosphamide and fludarabine were the most common LD regimen, but safety data were lacking.
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/m(2) 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.
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