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Introduction: The purpose of the present analysis was to explore the cost-effectiveness of tisagenlecleucel in relapsed or refractory (r/r) paediatric acute lymphoblastic leukaemia (pALL) and r/r adult diffuse large B-cell lymphoma (DLBCL) in Switzerland against a range of historical standard-of-care treatments., Methods: Two cost-utility models were constructed for the two licensed indications using similar methodologies but indication-specific data. Clinical efficacy data were based on pooled analyses of clinical trials for tisagenlecleucel (pALL: ELIANA, ENSIGN, B2101J; DLBCL: JULIET, NCT02030834) and published data for comparator treatments. Treatment effects were compared based on matching-adjusted indirect comparison (MAIC) analyses. Four clinical lymphoma and leukaemia experts provided Switzerland-specific input regarding comparators, diagnostic and therapeutic procedures, clinical evidence and costs, which were used to inform the models. The base case analysis reflected the perspective of the Swiss mandatory health insurance system. Deterministic, probabilistic and scenario analyses were carried out to explore the robustness of results., Results: The base case analysis resulted in incremental costs of CHF 31,961-CHF 36,419 per quality-adjusted life year (QALY) gained for pALL across the different comparators and CHF 113,179 for DLBCL (1 CHF = 1.09 USD). Incremental costs per life-year gained ranged between CHF 33,906-CHF 97,399 across the two indications. Including productivity gains, tisagenlecleucel was shown to be dominant (more effective and less costly) over all the comparators for pALL and to result in incremental costs per life-year gained of CHF 57,324 for DLBCL., Conclusion: Using hypothetical willingness-to-pay thresholds of CHF 100,000-150,000 per QALY gained, the present analysis has shown tisagenlecleucel to be a cost-effective treatment option in pALL and DLBCL.