Cost-effectiveness analysis 3L of axicabtagene ciloleucel vs tisagenlecleucel and lisocabtagene maraleucel in Japan.
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SUBMITTER: Tsutsue S
PROVIDER: S-EPMC11321402 | biostudies-literature | 2024
REPOSITORIES: biostudies-literature
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Cost-effectiveness analysis 3L of axicabtagene ciloleucel vs tisagenlecleucel and lisocabtagene maraleucel in Japan.
Tsutsué Saaya S Makita Shinichi S Asou Hiroya H Matsuda Hiroyuki H Yamaura Reiko R Taylor Todd D TD
Future oncology (London, England) 20240410 19
<b>Aim:</b> Cost-effectiveness analysis (CEA) was performed to compare axicabtagene ciloleucel (axi-cel) with tisagenlecleucel (tisa-cel) and lisocabtagene (liso-cel) for treatment of relapsed or refractory large B-cell lymphoma in adult patients after ≥2 lines of therapy in Japan. <b>Materials & methods:</b> Cost-effectiveness analysis was conducted using the partition survival mixture cure model based on the ZUMA-1 trial and adjusted to the JULIET and TRANSCEND trials using matching-adjusted i ...[more]
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| S-EPMC11568755 | biostudies-literature
Project description:IntroductionThe objective of this study was to evaluate the cost-effectiveness of lisocabtagene maraleucel (liso-cel) versus other available chimeric antigen receptor T-cell therapies, including axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel), in patients who had received at least two prior therapies from a United States (US) commercial third-party payer perspective.MethodsTo capture this heterogeneity in survival outcomes, we used mixture cure models to extrapolate progression-free survival (PFS) and overall survival (OS). Patient-level data from TRANSCEND NHL 001 for liso-cel and reconstructed patient-level data from ZUMA-1 for axi-cel, JULIET for tisa-cel, and SCHOLAR-1 for salvage chemotherapy, derived using the Guyot method, were used for OS and PFS. The model included adverse events associated with liso-cel, axi-cel, and tisa-cel.ResultsLiso-cel was less costly (incremental cost of - $74,980) and marginally more effective (0.002 incremental quality-adjusted life-years [QALY]) than axi-cel and had an incremental cost of $67,925 and 2.02 incremental QALYs over tisa-cel in the base case. Results remained consistent in sensitivity analyses, with the liso-cel OS cure fraction being the main driver of cost-effectiveness compared with both axi-cel and tisa-cel.ConclusionThis analysis estimated that liso-cel is cost-effective compared with tisa-cel and axi-cel from a commercial US payer perspective.
| S-EPMC10129927 | biostudies-literature
Project description:BackgroundCurrently, three chimeric antigen receptor (CAR)-T cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have been approved by the U.S. Food and Drug Administration for the treatment of large B cell lymphoma, which provide a novel and promising choice for patients with relapsed or refractory to traditional anti-tumor treatments. Thus, it is pertinent to describe the efficacy and safety profile of the three products available by summarizing the current evidence.MethodsTwo reviewers independently searched the Embase, PubMed, Web of Science, and Cochrane Library, to identify studies related to the use of the three CAR-T cell products for treating hematologic malignancies published up to October 5, 2020. We pooled the overall response rate, complete response rate, cytokine release syndrome, and immune effector cell-associated neurotoxicity syndrome of three products, and then performed subgroup analysis based on the type of product and type of tumor.ResultsThirty-three studies involving 2,172 patients were included in the analysis. All three products showed promising results in patients with different pathological subtypes and clinical characteristics that included those who did not meet the eligibility criteria of licensing trials, with overall response rates of nearly 70% or above and complete response rates of more than 50%. However, high rates of severe immune effector cell-associated neurotoxicity syndrome in patients undergoing axicabtagene ciloleucel treatment and life-threatening cytokine release syndrome in patients with leukemia undergoing tisagenlecleucel treatment required special attention in practice (31%; 95% CI: 0.27-0.35 and 55%; 95% CI: 0.45-0.64, respectively). Moreover, lisocabtagene maraleucel that showed a favorable efficacy and safety in the licensing trial lacked corresponding real-world data.ConclusionBoth axicabtagene ciloleucel and tisagenlecleucel showed considerable efficacy in practice, but need special attention with respect to life-threatening toxicity that can occur in certain situations. Lisocabtagene maraleucel demonstrated excellent efficacy and safety profiles in the licensing trial, but lacked corresponding real-world data. Additional data on the three products are needed in rare histological subtypes to benefit a broader patient population.
| S-EPMC8350577 | biostudies-literature
Project description:AbstractLisocabtagene maraleucel (liso-cel) and axicabtagene ciloleucel (axi-cel) are anti-CD19 chimeric antigen receptor (CAR) T-cell therapies approved for relapsed and refractory large B-cell lymphoma (LBCL); however, there is currently no published data on liso-cel outside of clinical trials nor any data comparing these therapies. In this retrospective analysis, we reviewed patients with LBCL receiving liso-cel or axi-cel at a single institution in the third-line setting. From June 2021 to September 2022, a total of 50 patients received axi-cel and 37 liso-cel. Baseline patient characteristics were similar, aside from older age in liso-cel recipients. The median time from leukapheresis to CAR T-cell infusion was significantly longer for liso-cel (41 days) than axi-cel (30 days). Complete response rates were not significantly different between axi-cel (72%) and liso-cel (62%). At a median follow-up of 11 months, progression-free survival (PFS) was not significantly different between axi-cel and liso-cel cohorts, with 12-month PFS of 59% and 44%, respectively. However, on a propensity score analysis, an inferior PFS was observed with liso-cel (hazard ratio, 2.95; 95% confidence interval , 1.14-7.60). The rates of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and prolonged neutropenia were higher with axi-cel than liso-cel. Overall, direct comparison of axi-cel and liso-cel cohorts shows similar key outcomes including response rate and PFS, but prolonged wait times for liso-cel may have resulted in biased selection of patients with more favorable characteristics for liso-cel. When accounting for these higher-risk characteristics, an inferior PFS is observed with liso-cel compared with axi-cel. These findings warrant further evaluation in a multicenter setting.
| S-EPMC11808612 | biostudies-literature
Project description:ImportanceChimeric antigen receptor (CAR) T cell therapies are approved as a third-line or later therapy for several hematological malignant neoplasms. Recently, randomized clinical trials have investigated their efficacy as a second-line treatment in high-risk relapsed or refractory diffuse large B-cell lymphoma (DLBCL) compared with salvage chemotherapy followed by hematopoietic stem cell transplantation (HSCT).ObjectiveTo evaluate the cost-effectiveness of axicabtagene ciloleucel and tisagenlecleucel vs standard care (SC) as second-line or later therapy for relapsed or refractory DLBCL, from both US health care sector and societal perspectives at a cost-effectiveness threshold of $150 000 per quality-adjusted life-year (QALY).Design, setting, and participantsThis economic evaluation assessed cost-effectiveness using a partitioned survival model with 2021 US dollars and QALYs over a lifetime horizon. Model inputs were derived from 2 randomized clinical trials (ZUMA-7 and BELINDA) and published literature. In the trials, patients who did not respond to SC received CAR T cells (treatment switching or crossover), either outside the protocol (ZUMA-7) or as part of the protocol (BELINDA). A separate scenario analysis compared second-line axicabtagene ciloleucel with SC alone without treatment crossover to CAR T cell therapy. Data analysis was performed from December 18, 2021, to September 13, 2022.ExposuresCAR T cell therapy (axicabtagene ciloleucel and tisagenlecleucel) compared with salvage chemotherapy followed by HSCT.Main outcomes and measuresCosts and QALYs were used to derive incremental cost-effectiveness ratios (ICERs) for the health care sector and societal perspectives. Cost and QALYs were discounted at 3.0% annually. Univariate and multivariate probabilistic sensitivity analysis using 10 000 Monte Carlo simulations were applied to test model uncertainty on the ICER.ResultsSecond-line axicabtagene ciloleucel was associated with an ICER of $99 101 per QALY from the health care sector perspective and an ICER of $97 977 per QALY from the societal perspective, while second-line tisagenlecleucel was dominated by SC (incremental costs of $37 803 from the health care sector and $39 480 from the societal perspective with decremental QALY of -0.02). Third-line or later tisagenlecleucel was associated with an ICER of $126 593 per QALY from the health care sector perspective and an ICER of $128 012 per QALY from the societal perspective. Based on the scenario analysis of no treatment switching, second-line axicabtagene ciloleucel yielded an ICER of $216 790 per QALY from the health care sector perspective and an ICER of $218 907 per QALY from the societal perspective, compared with SC. When accounting for patients achieving prolonged progression-free survival who would not incur progression-related costs, in this scenario ICER changed to $125 962 per QALY from the health care sector perspective and $122 931 per QALY from the societal perspective. These results were most sensitive to increased list prices of CAR T cell therapy and QALY losses associated with axicabtagene ciloleucel and tisagenlecleucel.Conclusions and relevanceThese findings suggest that second-line axicabtagene ciloleucel and third-line or later tisagenlecleucel were cost-effective in treating patients with relapsed or refractory DLBCL at the cost-effectiveness threshold of $150 000 per QALY. However, uncertainty remains regarding the best candidates who would experience value gains from receiving CAR T cell therapy.
| S-EPMC9856352 | biostudies-literature
Project description:ImportanceAxicabtagene ciloleucel, a chimeric antigen receptor T-cell therapy, represents a new and potentially curative treatment option for B-cell lymphoma. It is expected to have long-term survival benefits; however, long-term survival data are limited.ObjectiveTo estimate the long-term survival and cost-effectiveness of axicabtagene ciloleucel for treatment of relapsed or refractory B-cell lymphoma.Design, setting, and participantsEconomic evaluation study using a survival analysis that digitized and extrapolated survival curves published in the ZUMA-1 trial (Safety and Efficacy of KTE-C19 in Adults With Refractory Aggressive Non-Hodgkin Lymphoma), which enrolled patients between November 2015 and September 2016 and had a maximum follow-up of 24 months. Five different survival models (standard parametric, flexible parametric, 2 mixture cure models, and a flexible parametric mixture model) were used to extrapolate the survival curves to a lifetime horizon from January through June 2018. A cost-effectiveness analysis, from both a trial-based and lifetime horizon, was also conducted to inform the value of this novel therapy. The model was based on data from 111 patients with B-cell lymphoma who were enrolled in the ZUMA-1 trial.InterventionsOne-time administration of axicabtagene ciloleucel compared with chemotherapy.Main outcomes and measuresUndiscounted and discounted life-years (LYs) and quality-adjusted life-years (QALYs), total costs, and incremental costs per LY and QALY gained.ResultsThe modeled cohort of 111 patients started at 58 years of age. At the end of the trial, treatment with axicabtagene ciloleucel resulted in 0.48 more LYs and 0.34 more QALYs than chemotherapy, producing a cost-effectiveness estimate of $896 600 per QALY for public payers and $1 615 000 per QALY for commercial payers. Extrapolated long-term survival for patients treated with axicabtagene ciloleucel ranged from 2.83 to 9.19 discounted LYs and from 2.07 to 7.62 discounted QALYs. Incrementally, treatment with axicabtagene ciloleucel was associated with 1.89 to 5.82 discounted LYs and 1.52 to 4.90 discounted QALYs vs chemotherapy. With the use of these incremental estimates of survival, cost-effectiveness estimates ranged from $82 400 to $230 900 per QALY gained for public payers and from $100 400 to $289 000 per QALY gained for commercial payers.Conclusions and relevanceTreatment with axicabtagene ciloleucel appears to be associated with incremental gains in survival over chemotherapy. The range in projected long-term survival was wide and reflected uncertainty owing to limited follow-up data. Cost-effectiveness is associated with long-term survival, with further evidence needed to reduce uncertainty.
| S-EPMC6484589 | biostudies-literature
Project description:AbstractLisocabtagene maraleucel (liso-cel), a chimeric antigen receptor (CAR) T-cell therapy, received the US Food and Drug Administration approval in 2022 for second-line treatment of diffuse large B-cell lymphoma (DLBCL) for patients with refractory disease or early relapse after first-line chemoimmunotherapy. This decision was based on the TRANSFORM study demonstrating improvements in event-free survival with liso-cel compared with standard care. Given the high costs of CAR T-cell therapies, particularly as they transition to second-line treatment, a cost-effectiveness analysis is essential to determine their economic viability. The study used a partitioned survival model with standard parametric functions to evaluate the cost-effectiveness of liso-cel aganist platinum-based chemotherapy followed by high-dose chemotherapy and autologous hematopoietic stem cell transplantation over a lifetime horizon The analysis relied on data from the TRANSFORM and TRANSCEND trials, established literature, and public data sets to calculate the incremental cost-effectiveness ratio (ICER). For a representative cohort of US adults aged 60 years, ICER of liso-cel was $99 669 per quality-adjusted life-year (QALY) from a health care sector perspective and $68 212 per QALY from a societal perspective, confirming its cost-effectiveness at the $100 000 per QALY threshold. Nonetheless, under certain scenarios, liso-cel surpasses this benchmark but remains within the US acceptable range of $150 000 per QALY. A key finding underlines the importance of incorporating productivity losses into such analyses to capture the broader societal values of novel therapies. Although these therapies offer substantial clinical benefits, their high acquisition costs and limited long-term data critically challenge their economic sustainability.
| S-EPMC10837180 | biostudies-literature
Project description:The ZUMA-7 (Efficacy of Axicabtagene Ciloleucel Compared to Standard of Care Therapy in Subjects With Relapsed/Refractory Diffuse Large B Cell Lymphoma) study showed that axicabtagene ciloleucel (axi-cel) improved event-free survival (EFS) compared with standard of care (SOC) salvage chemoimmunotherapy followed by autologous stem cell transplant in primary refractory/early relapsed diffuse large B-cell lymphoma (DLBCL); this led to its recent US Food and Drug Administration approval in this setting. We modeled a hypothetical cohort of US adults (mean age, 65 years) with primary refractory/early relapsed DLBCL by developing a Markov model (lifetime horizon) to model the cost-effectiveness of second-line axi-cel compared with SOC using a range of plausible long-term outcomes. EFS and OS were estimated from ZUMA-7. Outcome measures were reported in incremental cost-effectiveness ratios, with a willingness-to-pay (WTP) threshold of $150 000 per quality-adjusted life-year (QALY). Assuming a 5-year EFS of 35% with second-line axi-cel and 10% with SOC, axi-cel was cost-effective at a WTP of $150 000 per QALY ($93 547 per QALY). axi-cel was no longer cost-effective if its 5-year EFS was ≤26.4% or if it cost more than $972 061 at a WTP of $150 000. Second-line axi-cel was the cost-effective strategy in 73% of the 10 000 Monte Carlo iterations at a WTP of $150 000. If the absolute benefit in EFS is maintained over time, second-line axi-cel for aggressive relapsed/refractory DLBCL is cost-effective compared with SOC at a WTP of $150 000 per QALY. However, its cost-effectiveness is highly dependent on long-term outcomes. Routine use of second-line chimeric antigen receptor T-cell therapy would add significantly to health care expenditures in the United States (more than $1 billion each year), even when used in a high-risk subpopulation. Further reductions in the cost of chimeric antigen receptor T-cell therapy are needed to be affordable in many regions of the world.
| S-EPMC9837443 | biostudies-literature
Project description:Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are chimeric antigen receptor (CAR) T-cell therapies used to treat adult patients with relapsed or refractory follicular lymphoma (rrFL) after two or more lines of systemic therapy. In the absence of head-to-head clinical trials, this study aimed to compare the efficacy, safety, and cost of axi-cel and tisa-cel in the treatment of rrFL after at least two lines of treatment. Overall response rate (ORR) and safety signals were compared using reporting odds ratios (RORs) with 95% confidence intervals (CIs) at p < 0.05. Progression-free survival (PFS), duration of response (DoR), and overall survival (OS) were compared using the Kaplan?Meier method with a log-rank test. Cost and cost-minimization analyses of drug acquisition, drug administration, serious adverse events (AEs), and relapsed management were calculated. Costs were extracted from the IBM-Micromedex Red Book, Centers for Medicare and Medicaid Services, and existing literature. Statistical analyses were conducted using Microsoft Excel and R version 4.0.5. No statistically significant differences were observed between axi-cel and tisa-cel in terms of ORR, DoR, and OS (p > 0.05). PFS was significantly better with tisa-cel (p < 0.05). Axi-cel was significantly associated with higher incidences of CRS, neurologic events, and grade 3-4 AEs than tisa-cel (ROR > 1, p < 0.05). Axi-cel and tisa-cel cost $512,021 and $450,885 per patient, respectively, resulting in savings of US$61,136 with tisa-cel over axi-cel. Tisa-cel appears to have a better safety profile, fewer serious AEs, lower mortality rate, and lower cost than axi-cel.
| S-EPMC10560186 | biostudies-literature
Project description:Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed chimeric antigen receptor T cell (CAR-T) therapies approved for relapsed/refractory aggressive large B cell lymphoma (LBCL). Significant costs and complex manufacturing underscore the importance of evidence-based counseling regarding the outcomes of these treatments. With the aim of examining the efficacy and safety of axi-cel versus tisa-cel in patients with relapsed/refractory aggressive LBCL, we performed a systematic literature search of comparative studies evaluating outcomes in relapsed/refractory aggressive LBCL after treatment with axi-cel or tisa-cel. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) for response, progression-free survival (PFS), overall survival (OS), cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and hematotoxicity. Meta-analysis and meta-regression were used to generate summary statistics. A total of 2372 participants were included in the 8 studies in our analysis. The dropout rate between apheresis and infusion was 13% for axi-cel versus 18% for tisa-cel, and the median time from apheresis to infusion was 32 days versus 45 days. Axi-cel showed higher odds for a complete response (OR, 1.65; P < .001) and was associated with higher odds for PFS at 1 year after infusion (OR, .60; P < .001). OS appeared to be improved with axi-cel (OR, .84; 95% CI, .68 to 1.02; P = .08), whereas the cumulative incidence of nonrelapse mortality (NRM) was 11.5% for axi-cel versus 3.7% for tisa-cel (P = .002). The main predictors for survival were lactate dehydrogenase level, Eastern Cooperative Oncology Group Performance Status, and response to bridging, and axi-cel maintained superior efficacy even in elderly patients. In terms of safety, axi-cel was associated with significantly higher odds of any-grade CRS (OR, 3.23; P < .001), but not of grade ≥3 CRS (P = .92). Axi-cel was associated with significantly higher odds of severe ICANS grade ≥3 (OR, 4.03; P < .001). In terms of hematotoxicity, axi-cel was significantly associated with higher odds of severe neutropenia at 1 month after infusion (OR, 2.06; P = .003). As a result, axi-cel was associated with significantly greater resource utilization, including prolonged hospital stay, more frequent intensive care admission, and use of agents such as tocilizumab for toxicity management. We provide strong evidence of the greater efficacy of axi-cel versus tisa-cel in relapsed/refractory aggressive LBCL. The higher toxicity and NRM seen with axi-cel might not counterbalance the overall results, highlighting the need for timely intervention and careful selection of patients, balancing resource utilization and clinical benefit.
| S-EPMC11771143 | biostudies-literature