ALL-190: Cost-Effectiveness of KTE-X19 for Adult Patients with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL) in the United States

Context: KTE-X19 is a chimeric antigen receptor T-cell therapy that demonstrated efficacy with a median overall survival (OS) of 18.2 months in relapsed/refractory (R/R) adult acute lymphoblastic leukemia (aALL) patients in the pivotal ZUMA-3 trial (NCT02614066). Trials for recently approved treatments in the same setting reported median OS of fewer than 8 months. Objective: This study estimated the cost-effectiveness of KTE-X19 versus major comparators: blinatumomab (blin), inotuzumab ozogamicin (ino), and salvage chemotherapy (chemo) to treat R/R aALL patients from a US payer perspective. Design: A three-state partitioned-survival model (pre-progression survival [PPS], disease progression, and death) with a weekly cycle length estimated health outcomes and costs over a lifetime horizon. Efficacy and safety data, allogeneic stem cell transplant (allo-SCT) rates, and health state utilities were sourced directly from pivotal trials (e.g., ZUMA-3 phase 2 mITT, TOWER, INO-VATE). A mixture-cure model was used to extrapolate PPS and OS, assuming patients without disease progression after two years experienced long-term remission. Costs (including acquisition, administration, monitoring, allo-SCT, subsequent treatments, adverse events, and terminal care) were obtained from published sources. Costs and health outcomes were discounted at 3% annually. Interventions: KTE-X19 and comparators: blin, ino, and chemo. Main Outcomes Measures: The model estimated expected life years (LYs), quality-adjusted life years (QALYs), total costs for all treatments, and pairwise incremental cost-effectiveness ratios (ICERs). Results: The model showed that the incremental LY and QALY gains for KTE-X19 versus comparators were: 2.86 and 2.54 (versus blin); 4.01 and 3.37 (versus ino); and 5.65 and 4.74 (versus chemo). The incremental costs for X19 versus comparators were $51,845 (versus blin), $225,046 (versus ino), $429,720 (versus chemo), respectively. Incremental costs and QALYs gains resulted in an ICER of $20,413/QALY versus blin, $66,839/QALY versus ino, and $90,672/QALY versus chemo. At a willingness-to-pay threshold of $150,000/QALY, probabilistic sensitivity analysis demonstrated that KTE-X19 has a 92.3%, 90.2%, and 79.6% probability of being cost-effective versus blin, ino, and chemo, respectively. Conclusions: KTE-X19 is a cost-effective treatment compared to standard of care options for R/R aALL in the US. Therefore, KTE-X19 is an economically and clinically effective option to add to the current treatment landscape. KTE-X19 is a chimeric antigen receptor T-cell therapy that demonstrated efficacy with a median overall survival (OS) of 18.2 months in relapsed/refractory (R/R) adult acute lymphoblastic leukemia (aALL) patients in the pivotal ZUMA-3 trial (NCT02614066). Trials for recently approved treatments in the same setting reported median OS of fewer than 8 months. This study estimated the cost-effectiveness of KTE-X19 versus major comparators: blinatumomab (blin), inotuzumab ozogamicin (ino), and salvage chemotherapy (chemo) to treat R/R aALL patients from a US payer perspective. A three-state partitioned-survival model (pre-progression survival [PPS], disease progression, and death) with a weekly cycle length estimated health outcomes and costs over a lifetime horizon. Efficacy and safety data, allogeneic stem cell transplant (allo-SCT) rates, and health state utilities were sourced directly from pivotal trials (e.g., ZUMA-3 phase 2 mITT, TOWER, INO-VATE). A mixture-cure model was used to extrapolate PPS and OS, assuming patients without disease progression after two years experienced long-term remission. Costs (including acquisition, administration, monitoring, allo-SCT, subsequent treatments, adverse events, and terminal care) were obtained from published sources. Costs and health outcomes were discounted at 3% annually. KTE-X19 and comparators: blin, ino, and chemo. The model estimated expected life years (LYs), quality-adjusted life years (QALYs), total costs for all treatments, and pairwise incremental cost-effectiveness ratios (ICERs). The model showed that the incremental LY and QALY gains for KTE-X19 versus comparators were: 2.86 and 2.54 (versus blin); 4.01 and 3.37 (versus ino); and 5.65 and 4.74 (versus chemo). The incremental costs for X19 versus comparators were $51,845 (versus blin), $225,046 (versus ino), $429,720 (versus chemo), respectively. Incremental costs and QALYs gains resulted in an ICER of $20,413/QALY versus blin, $66,839/QALY versus ino, and $90,672/QALY versus chemo. At a willingness-to-pay threshold of $150,000/QALY, probabilistic sensitivity analysis demonstrated that KTE-X19 has a 92.3%, 90.2%, and 79.6% probability of being cost-effective versus blin, ino, and chemo, respectively. KTE-X19 is a cost-effective treatment compared to standard of care options for R/R aALL in the US. Therefore, KTE-X19 is an economically and clinically effective option to add to the current treatment landscape.