Two-year follow-up of KTE-X19 in patients with relapsed or refractory adult B-cell acute lymphoblastic leukemia in ZUMA-3 and its contextualization with SCHOLAR-3, an external historical control study.

BACKGROUND: Brexucabtagene autoleucel (KTE-X19) is an autologous anti-CD19 CAR T-cell therapy approved in the USA to treat adult patients with relapsed or refractory B-precursor acute lymphoblastic leukemia (R/R B-ALL) based on ZUMA-3 study results. We report updated ZUMA-3 outcomes with longer follow-up and an extended data set along with contextualization of outcomes to historical standard of care. METHODS: Adults with R/R B-ALL received a single infusion of KTE-X19 (1 × 106 CAR T cells/kg). Long-term post hoc subgroup assessments of ZUMA-3 were conducted. Outcomes from matched patients between historical clinical trials and ZUMA-3 patients were assessed in the retrospective historical control study SCHOLAR-3. RESULTS: After 26.8-months median follow-up, the overall complete remission (CR) rate (CR + CR with incomplete hematological recovery) among treated patients (N = 55) in phase 2 was 71% (56% CR rate); medians for duration of remission and overall survival (OS) were 14.6 and 25.4 months, respectively. Most patients responded to KTE-X19 regardless of age or baseline bone marrow blast percentage, but less so in patients with > 75% blasts. No new safety signals were observed. Similar outcomes were observed in a pooled analysis of phase 1 and 2 patients (N = 78). In SCHOLAR-3, the median OS for treated patients from ZUMA-3 (N = 49) and matched historical controls (N = 40) was 25.4 and 5.5 months, respectively. CONCLUSIONS: These data, representing the longest follow-up of CAR T-cell therapy in a multicenter study of adult R/R B-ALL, suggest that KTE-X19 provides a clinically meaningful survival benefit with manageable toxicity in this population. TRIAL REGISTRATION: NCT02614066.

Cost-Effectiveness of KTE-X19 for Adults with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia in the United States.

INTRODUCTION: Despite currently available treatments for adults with relapsed/refractory acute lymphoblastic leukemia (R/R ALL), survival outcomes remain poor, highlighting the need for new therapeutic strategies. This study estimates the cost-effectiveness of KTE-X19 to treat adults with R/R ALL from a US payer perspective. METHODS: The model had two components: a decision-tree, where pre-infusion costs for patients who ultimately did not receive KTE-X19 are accounted for, followed by a partitioned survival analysis, where all KTE-X19 infused patients would enter the three-state (pre-progression, progressed disease, death) model. Comparators included current standard of care treatments, i.e., blinatumomab (BLIN), inotuzumab ozogamicin (INO), and salvage chemotherapy (CHEMO). Both standard parametric and mixture cure models were used to model survival. Efficacy, safety, healthcare resource utilization, and health state utility inputs were derived from the ZUMA-3 trial (NCT02614066) and literature. Cost inputs were derived from literature or publicly available sources. Outcomes and costs were discounted 3% annually. Results of KTE-X19 versus comparators are reported as total and incremental life-years (LYs), quality-adjusted life-years (QALYs), costs, and resulting incremental cost-effectiveness ratio (ICER). Deterministic and probabilistic sensitivity analyses (PSA) and key scenario analyses were also performed. RESULTS: In the base case, incremental QALYs for KTE-X19 were 2.44, 3.26, and 4.61 versus BLIN, INO, and CHEMO, respectively. Incremental costs were $50,913, $251,532, and $432,027, respectively, resulting in ICERs of $20,843/QALY (versus BLIN), $77,271/QALY (versus INO), and $93,768/QALY (versus CHEMO). Deterministic sensitivity analysis results were most sensitive to subsequent allogeneic stem cell transplant rates and post-progression utilities. PSA found that KTE-X19 is 78.4%, 74.0%, and 75.4% likely to be cost-effective versus BLIN, INO, and CHEMO, respectively. Across most scenarios, at a willingness-to-pay (WTP) threshold of $150,000/QALY, KTE-X19 was cost-effective versus all treatments. CONCLUSIONS: Compared to current options for adults with R/R ALL, KTE-X19 is cost-effective, driven primarily by improved survival.

Several treatments for adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (R/R B-ALL) have been approved in the past decade in the US, including blinatumomab (BLIN) and inotuzumab ozogamicin (INO). However, despite the high costs associated with these treatments, survival for patients remains poor. KTE-X19, an autologous anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy, approved by the Food and Drug Administration in October 2021, has potential to improve survival, but its economic value has not yet been determined. This model comprehensively evaluated the long-term clinical and economic value of KTE-X19 versus current treatments, including BLIN, INO, and salvage chemotherapy (CHEMO). Inputs were derived from key clinical trials, the literature, and other publicly available sources. The model used the perspective of a US third party payer over a patient lifetime. Compared to BLIN, INO and CHEMO, KTE-X19 resulted in improved quality of life as measured with incremental quality-adjusted life years (QALYs) of 2.44 (vs BLIN), 3.26 (vs INO), and 4.61 (vs CHEMO). Treatment with KTE-X19 had incremental costs of $50,913 (vs BLIN), $251,532 (vs INO), and $432,027 (vs CHEMO). KTE-X19 was found to provide good value for money based on incremental cost-effectiveness ratios of $20,843/QALY (vs BLIN), $77,271/QALY (vs INO), and $93,768/QALY (vs CHEMO). These values are well below the commonly accepted thresholds to determine economic value. Results were also found to be robust across sensitivity and scenario analyses.