Cost-Effectiveness Analysis of Tisagenlecleucel for the Treatment of Pediatric and Young Adult Patients with Relapsed or Refractory B Cell Acute Lymphoblastic Leukemia in Japan.

Until recently, treatment options were relatively limited for children and young adults with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL). Tisagenlecleucel is a chimeric antigen receptor T cell (CAR-T) immunotherapy with promising efficacy and manageable safety that was approved in Japan in 2019 for the treatment of CD19-positive r/r B cell ALL (B-ALL). However, there is no publication assessing the cost-effectiveness of CAR-T in Japan. The objective of this study was to assess the cost-effectiveness of a tisagenlecleucel treatment strategy compared to a blinatumomab treatment strategy and a clofarabine combination treatment strategy (i.e., clofarabine + cyclophosphamide + etoposide) in Japan for pediatric and young adult patients up to 25 years of age with r/r B-ALL. A partitioned survival model with a lifetime horizon and monthly cycle was constructed from a Japanese public healthcare payer's perspective. Patients were distributed across the following partitioned health states: event-free survival (EFS), progressive disease, and death, which were informed by the EFS and overall survival (OS) data of respective clinical trials before year 5. For the tisagenlecleucel arm, a decision-tree structure was used to partition patients based on the infusion status; those who discontinued prior to receiving infusion were assigned efficacy and cost inputs of blinatumomab and those who received infusion were assigned efficacy and costs inputs based on tisagenlecleucel-infused patients. As trial data for blinatumomab and clofarabine ended before year 5, matching-adjusted indirect comparisons were used to extrapolate OS between the end of trial observation and up to year 5. All surviving patients followed the mortality risk of long-term ALL survivors without additional risk of disease relapse after year 5, regardless of initial treatment strategies. The model accounted for pretreatment costs, treatment costs, adverse event costs, follow-up costs, subsequent allogeneic hematopoietic stem cell transplantation costs, and terminal care costs. Incremental cost-effectiveness ratios (ICERs) per life-years (LYs) gained and ICERs per quality-adjusted life-years (QALYs) gained were evaluated using a 2% discount rate, and a threshold of ¥7.5 million was used to assess cost-effectiveness. Deterministic and probabilistic sensitivity analyses were performed. The total LYs (discounted) for tisagenlecleucel, blinatumomab, and clofarabine combination treatment strategies were 13.3, 4.0, and 2.7 years, respectively; the corresponding QALYs were 11.6, 3.1, and 2.1 years, respectively. The ICERs per QALY gained for tisagenlecleucel were ¥2,035,071 versus blinatumomab and ¥2,644,702 versus clofarabine combination therapy. Extensive sensitivity analyses supported the findings. Tisagenlecleucel is a cost-effective treatment strategy for pediatric and young adult patients with r/r B-ALL from a Japanese public healthcare payer's perspective.

Wakase S ，Teshima T ，Zhang J ，Ma Q ，Watanabe Y ，Yang H ，Qi CZ ，Chai X ，Xie Y ，Wu EQ ，Igarashi A ... -  《-》

Cost Effectiveness Analysis of Tisagenlecleucel for the Treatment of Adult Patients with Relapsed or Refractory Diffuse Large B Cell Lymphoma in Japan.

There are limited treatment options and substantial unmet needs for adult patients with relapsed or refractory diffuse large B cell lymphoma (r/r DLBCL) in Japan. In 2019, tisagenlecleucel, a CD19-directed chimeric antigen receptor T cell therapy, was approved for r/r DLBCL in Japan. The efficacy and safety of tisagenlecleucel were demonstrated in the pivotal phase II single-arm JULIET trial. The objective of the current study was to assess the cost-effectiveness of tisagenlecleucel treatment strategy versus current standard of care (salvage chemotherapy treatment strategy) for the treatment of patients with r/r DLBCL in Japan. A three-state partitioned survival model was constructed from a Japanese public healthcare payer's perspective, with the following three health states: progression-free survival, progressive/relapsed disease, and death. Because the tisagenlecleucel arm included patients who did or did not receive the infusion, a decision-tree structure was used to partition patients based on their infusion status. Treatment efficacy and costs were based on tisagenlecleucel-infused patients for those who received the infusion; for non-infused patients, they were based on standard salvage chemotherapy. The efficacy inputs for tisagenlecleucel-infused patients and salvage chemotherapy were based on observed data in the JULIET trial and the international SCHOLAR-1 meta-analysis, respectively, before year 3. Afterward, all patients were assumed to have no further progression and to incur the mortality risk of long-term DLBCL survivors. The base case analysis explored a lifetime horizon (44 years), with costs and effectiveness discounted 2.0% annually, and it used a monthly model cycle. Direct costs were considered in the base case, composed of pretreatment costs, treatment costs, adverse events management costs, follow-up costs before progression, subsequent SCT costs, post-progression costs, and terminal care costs. Total incremental costs, life years (LYs), and quality-adjusted life years (QALYs) were compared for tisagenlecleucel versus salvage chemotherapy. The incremental cost-effectiveness ratio (ICER) was estimated as the costs per QALY gained, and a threshold of ¥7.5 million was used to assess whether tisagenlecleucel is cost effective. Deterministic and probabilistic sensitivity analyses were performed. The total LYs (discounted) for tisagenlecleucel and salvage chemotherapy were 7.24 and 4.35 years, respectively; the corresponding QALYs were 5.42 and 2.57 years, respectively. The discounted incremental LYs and QALYs comparing tisagenlecleucel to salvage chemotherapy were estimated as 2.89 and 2.85 years, respectively. Over a lifetime horizon, the model estimated that tisagenlecleucel had a total incremental cost of ¥15,590,335 (discounted) versus salvage chemotherapy. Tisagenlecleucel was associated with an ICER of ¥5,476,496 per QALY gained compared to salvage chemotherapy. Extensive sensitivity analyses supported the base-case findings. Tisagenlecleucel is a cost-effective treatment strategy for r/r DLBCL compared to salvage chemotherapy treatment strategy from a Japanese public healthcare payer's perspective.

Wakase S ，Teshima T ，Zhang J ，Ma Q ，Fujita T ，Yang H ，Chai X ，Qi CZ ，Liu Q ，Wu EQ ，Igarashi A ... -  《-》

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

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. 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. 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. Compared to current options for adults with R/R ALL, KTE-X19 is cost-effective, driven primarily by improved survival.

Shah BD ，Smith NJ ，Feng C ，Jeyakumar S ，Castaigne JG ，Faghmous I ，Masouleh BK ，Malone DC ，Bishop MR ... -  《-》

Long-term Survival and Value of Chimeric Antigen Receptor T-Cell Therapy for Pediatric Patients With Relapsed or Refractory Leukemia.

Whittington MD ，McQueen RB ，Ollendorf DA ，Kumar VM ，Chapman RH ，Tice JA ，Pearson SD ，Campbell JD ... -  《-》

Cost-effectiveness of Anti-CD19 chimeric antigen receptor T-Cell therapy in pediatric relapsed/refractory B-cell acute lymphoblastic leukemia. A societal view.

In several studies, the chimeric antigen receptor T-cell therapy tisagenlecleucel demonstrated encouraging rates of remission and lasting survival benefits in pediatric patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL). We assessed the cost-effectiveness of tisagenlecleucel (list price: 320 000 EUR) among these patients when compared to clofarabine monotherapy (Clo-M), clofarabine combination therapy (Clo-C), and blinatumomab (Blina) from both a healthcare and a societal perspective. We also assessed future medical and future non-medical consumption costs. A three-state partitioned survival model was used to simulate a cohort of pediatric patients (12 years of age) through different disease states until the end of life (lifetime horizon). Relevant outcomes were life years, quality-adjusted life years (QALYs), healthcare costs, societal costs, and the incremental cost-effectiveness ratio (ICER). Uncertainty was explored through deterministic and probabilistic sensitivity analyses as well as through several scenario analyzes. Total discounted costs for tisagenlecleucel were 552 679 EUR from a societal perspective, which was much higher than the total discounted costs from a healthcare perspective (ie, 409 563 EUR). Total discounted societal costs for the comparator regimens ranged between 160 803 EUR for Clo-M and 267 259 EUR for Blina. Highest QALYs were estimated for tisagenlecleucel (11.26), followed by Blina (2.25), Clo-C (1.70) and Clo-M (0.74). Discounted societal ICERs of tisagenlecleucel ranged between 31 682 EUR/QALY for Blina and 37 531 EUR/QALY for Clo-C and were considered cost-effective with a willingness-to-pay (WTP) threshold of 80 000 EUR/QALY. None of the scenarios exceeded this threshold, and more than 98% of the iterations in the probabilistic sensitivity analysis were cost-effective. At the current price and WTP threshold, tisagenlecleucel is cost-effective from both a healthcare and a societal perspective. Nevertheless, long-term effectiveness data are needed to validate the several assumptions that were necessary for this model.

Thielen FW ，van Dongen-Leunis A ，Arons AMM ，Ladestein JR ，Hoogerbrugge PM ，Uyl-de Groot CA ... -  《-》