OBJECTIVES: Review of prior ITCs is currently not required by most HTAs; however, with increasing number of regulatory approvals based on single-arm studies, the use of un-anchored population-adjusted ITCs (PAICs) is increasing. We explored how prior ITCs may be used to inform HTA strategy.

METHODS: Living-SLR database (LiveSLR®) was used to gather published ITCs/PAICs in RR-DLBCL patients not eligible for CAR-Ts; Published Hazard Ratios (HRs) were extracted and used to construct an ITC network; confidence intervals (CIs) were adjusted to account for multiple comparisons. Based on ongoing randomized-controlled trials (RCTs), we considered four RCTs (n=150/arm) of the hypothetical treatment “Squirlitinib” vs bendamustine+rituximab (BR), rituximab+gemcitabine+oxaliplatin (R-GemOx), polatuzumab+bendamustine+rituximab (POLA-BR), and tafasitamab+lenalidomide (TAFA-LEN). A Bayesian Living-Network-Meta-Analysis tool (LiveNMA®) was used to evaluate the HR required for Squirlitinib to achieve top NMA ranking versus all comparators.

RESULTS: Living-NMA PFS network consisted of four interventions: TAFA-LEN,POLA-BR, BR, and R-Gem-Ox. There was one RCT comparing POLA-BR vs. BR; three un-anchored ITCs using KM digitalization, three matched-adjusted ITCs (MAIC) and three external-control arm studies (ECA) using real-world evidence comparing TAFA-LEN with POLA-BR, BR, and R-Gem-Ox. HR<=0.37 (CI:0.17-0.57) vs. BR will be required for Squirlitinib to achieve the top ranking, while HR<=0.49 (CI:0.29-0.69) vs. R-GemOx, HR<=0.81 (CI:0.61-0.99) vs. POLA-BR, and any significant HR vs. TAFA-LEN will be sufficient to achieve top NMA ranking vs. all comparators (1-Squirlitinib, 2-TAFA-LEN, 3-POLA-BR, 4-R-GemOx, and 5-BR). Sensitivity analyses using only RCT+un-anchored ITCs or RCT+MAIC/ECA studies, did not change the outcome of the NMA and resultant ranking. HR estimates used here assume similar populations among studies – results should be interpreted cautiously and should only be used for strategic planning of future HEOR analyses.

CONCLUSIONS: Utilization of previously conducted ITCs may help with strategic HTA planning to ensure appropriate comparator use in pivotal trials and investigational drug effectiveness is sufficient to achieve HTA success.