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OBJECTIVE: The aim was to estimate the cost-effectiveness of inotuzumab ozogamicin (InO) versus standard of care chemotherapy (SoC) for adults with relapsed or refractory B cell acute lymphoblastic leukaemia (R/R ALL) in Sweden and Norway, and compare this to evaluations made by the health technology assessment (HTA) authorities Tandvårds- och läkemedelsförmånsverket (TLV) and the Norwegian Medicines Agency (NoMA). MATERIALS AND METHODS: A partitioned survival model was developed to determine incremental cost-effectiveness ratios (ICERs) for InO versus SoC. Parametric survival models were fit to overall survival and progression-free survival Kaplan-Meier data from the INO-VATE ALL phase III trial. Two base cases were run using (1) Swedish and (2) Norwegian inputs (costs and discount rates). Core clinical inputs and utilities did not differ between countries. Analyses were then conducted to reflect the preferred assumptions of TLV and NoMA. Univariate and multivariate sensitivity analyses were performed. RESULTS: The base case deterministic ICERs for InO versus SoC were 16,219/quality-adjusted life years (QALY) in Sweden (probabilistic 19,415) and 44,405/QALY in Norway (probabilistic 47,305). The ICERs using our model but applying the preferred assumptions of TLV or NoMA were 74,061/QALY (probabilistic 77,484) and 59,391/QALY (probabilistic 63,632), respectively. Differences between our base cases and the ICERs with TLV and NoMA settings were mainly explained by the exclusion of productivity costs and use of pooled post-haematopoietic stem-cell transplant (post-HSCT) survival in Sweden and use of higher HSCT costs in Norway. All ICERs remained below the approximated willingness-to-pay thresholds. The probability of InO being cost-effective ranged from 77 to 99% versus SoC. CONCLUSIONS: InO can likely be considered cost-effective versus SoC under our and the HTA-preferred settings.
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OBJECTIVE: Information about the long-term survival impact of hematopoietic stem cell transplant (HSCT) in adults with relapsed/refractory B-cell acute lymphoblastic leukaemia is limited. The objective was to conduct a systematic review identifying studies reporting survival in HSCT-receiving patients and apply parametric analyses to predict long-term survival. MATERIALS AND METHODS: Twenty-five relevant studies were identified. Analyses were conducted in 10 studies (n=503; "global" analysis) reporting overall survival (OS) data as Kaplan-Meier curves or at patient level. Four studies (n=217; "subgroup" analysis) measured OS from the point of HSCT. Patient-level data were recreated from Kaplan-Meier curves and pooled, with six models tested for longer-term extrapolation. Additionally, a sensitivity analysis was undertaken involving removal of data from the oldest study cohort (recruited between 1981-1997) to determine if the year which patients received HSCT impacted survival compared to post-2009 data. RESULTS: Median OS and five-year survival probability were 11.4 months and 24.4% (95% CI, 20.5-28.5%) in the global analysis, and 12.0 months and 28.4% (95% CI, 22.1-34.9%) in the subgroup analysis. The generalised gamma and Gompertz models fit longer-term extrapolation criteria. The generalised gamma model predicted survival at 10.4% vs. 14.8% (15 years), 8.3% vs. 12.8% (20 years), and 6.9% vs. 11.4% (25 years) for the global and subgroup analysis, respectively. The Gompertz model predicted survival to plateau at 23% vs. 25.6% just before 10 years. The sensitivity analysis excluding older data found median survival increased two-fold (25.3 vs. 12 months). CONCLUSIONS: Results synthesize long-term evidence of outcomes for HSCT-receiving patients, providing a basis for treatment comparison. Risk of death is low beyond four years and newer data appears correlated with improved outcomes.