The Cost-Effectiveness of Axicabtagene Ciloleucel as Second-Line Therapy in Patients with Large B-Cell Lymphoma in the United States: An Economic Evaluation of the ZUMA-7 Trial

Perales, Miguel Angel; Kuruvilla, John; Snider, Julia Thornton; Vadgama, Sachin; Blissett, Rob; El-Moustaid, Fadoua; Smith, Nathaniel J.; Patel, Ayushi; Johnston, Patrick B.

doi:10.1016/j.jtct.2022.08.010

Cited by 17 publications

(17 citation statements)

References 19 publications

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“…To achieve cost-effectiveness, the price of Axi-cel should be reduced appropriately. Similarly, based on ZUMA-7, Perales et al 32 used a mixture of cure models to extrapolate survival outcomes and concluded that second-line Axi-cel is cost-effective, with an ICER of $93,547/QALY. Our findings aligned with these results.…”

Section: Discussionmentioning

confidence: 99%

Cost-effectiveness analysis of axicabtagene ciloleucel as a second-line treatment for diffuse large B-cell lymphoma in China and the United States

Lei

Zhang

et al. 2023

Therapeutic Advances in Hematology

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Background: Axicabtagene ciloleucel (Axi-cel) is the first Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) product approved in China for treating adult patients with relapsed or refractory large B-cell lymphoma after receiving second-line or above systemic therapy. However, it cannot be widely used in clinical practice due to its high price. Objectives: To evaluate the economic value of Axi-cel fully in countries at different stages of economic development, this article, from the perspective of the medical and health system in China and the United States, evaluated the cost-effectiveness of Axi-cel in the second-line treatment of diffuse large B-cell lymphoma (DLBCL). Design: Cost effectiveness analysis of Axi-cel in the treatment of relapsed or refractory large B-cell lymphoma (LBCL). Methods: Based on the clinical trial data of ZUMA-7, a short-term decision tree and a long-term semi-Markov partitioned survival model were constructed to evaluate the cost-effectiveness of the two strategies. This model was cycled for 40 years in 1-month cycles. In this article, only direct medical costs were considered. One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to assess the robustness of the base-case results. Results: In the baseline cost-effectiveness analysis, Axi-cel was associated with more quality-adjusted life year (QALY; 2.72 versus 1.46) and greater costs overall ($180,501.55 versus $123,221.34) than standard second-line chemotherapy in China. Moreover, the incremental cost-effectiveness ratio (ICER) of the Axi-cel group was $45,726.66/QALY, which was greater than the threshold of $37,654.5. To achieve cost-effectiveness, the price of Axi-cel must be reduced appropriately. In the United States, Axi-cel was associated with more QALYs (2.63 versus 1.74) and greater costs overall ($415,915.16 versus $289,564.34). The ICER for the Axi-cel was $142,326.94/QALY, below the set threshold of $150,000. Conclusion: Axi-cel is not a cost-effective option as second-line therapy for treating DLBCL in China. However, In the United States, Axi-cel has shown a cost-effectiveness advantage as a second-line treatment for DLBCL.

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Section: Discussionmentioning

confidence: 99%

Cost-effectiveness analysis of axicabtagene ciloleucel as a second-line treatment for diffuse large B-cell lymphoma in China and the United States

Lei

Zhang

et al. 2023

Therapeutic Advances in Hematology

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“…In 2022, two other reports have been published suggesting that second-line axicabtagene ciloleucel would be cost-effective from US health care sector perspective . Perales and colleagues used a mixture of cure models to extrapolate survival outcomes from axicabtagene ciloleucel as reported in ZUMA-7 and concluded that second-line axicabtagene ciloleucel is a cost-effective treatment, with an ICER of $66 381 per QALY. Similarly, Kambhampati and colleagues concluded that second-line axicabtagene ciloleucel is cost-effective, with an ICER of $93 547 per QALY.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, Kambhampati and colleagues concluded that second-line axicabtagene ciloleucel is cost-effective, with an ICER of $93 547 per QALY. The study by Perales et al did not account for progression-related costs associated with CAR T cell crossover, while the study by Kambhampati et al modeled these outcomes based on the ZUMA-1 study. Our findings aligned with these results, although the standard parametric modeling approach that we used yields fewer mean survival gains than the mixture cure modeling approach and is considered more conservative …”

Section: Discussionmentioning

confidence: 99%

Cost-effectiveness of Axicabtagene Ciloleucel and Tisagenlecleucel as Second-line or Later Therapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

et al. 2022

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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.

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“…In the ZUMA-7 and TRANSFORM trials, second-line CAR-T cell therapy was shown to be superior to standard-of-care chemotherapy with or without autologous stem cell transplantation (ASCT) 11 , 12 , but less favorable survival was reported in primary refractory patients than in r/r DLBCL patients, highlighting the need for further improvement of efficacy in this population. Furthermore, approximately 60% of the patients in these trials experienced progressive disease (PD) following CAR-T cell therapy, with a median disease control period of 6 months 11 , 13 – 17 . Thus, understanding the mechanisms underlying resistance to CAR-T cell therapy in patients with primary refractory DLBCL is essential.…”

Section: Introductionmentioning

confidence: 99%

Cholesterol efflux from C1QB-expressing macrophages is associated with resistance to chimeric antigen receptor T cell therapy in primary refractory diffuse large B cell lymphoma

Yan,

Dong,

Qiao

et al. 2024

Nat Commun

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Chimeric antigen receptor T (CAR-T) cell therapy has demonstrated promising efficacy in early trials for relapsed/refractory diffuse large B cell lymphoma (DLBCL). However, its efficacy in treating primary refractory DLBCL has not been comprehensively investigated, and the underlying resistance mechanisms remain unclear. Here, we report the outcomes of a phase I, open-label, single-arm clinical trial of relmacabtagene autoleucel (relma-cel), a CD19-targeted CAR-T cell product, with safety and efficacy as primary endpoints. Among the 12 enrolled patients, 8 experienced grade 4 hematologic toxicity of treatment-emergent adverse event. No grade ≥3 cytokine release syndrome or neurotoxicity occurred. Single-cell RNA sequencing revealed an increase proportion of C1QB-expressing macrophages in patients with progressive disease before CAR-T cell therapy. Cholesterol efflux from M2 macrophages was found to inhibit CAR-T cells cytotoxicity by inducing an immunosuppressive state in CD8+ T cells, leading to their exhaustion. Possible interactions between macrophages and CD8+ T cells, mediating lipid metabolism (AFR1-FAS), immune checkpoint activation, and T cell exhaustion (LGALS9-HAVCR2, CD86-CTLA4, and NECTIN2-TIGIT) were enhanced during disease progression. These findings suggest that cholesterol efflux from macrophages may trigger CD8+ T cell exhaustion, providing a rationale for metabolic reprogramming to counteract CAR-T treatment failure. Chinadrugtrials.org.cn identifier: CTR20200376.

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The Cost-Effectiveness of Axicabtagene Ciloleucel as Second-Line Therapy in Patients with Large B-Cell Lymphoma in the United States: An Economic Evaluation of the ZUMA-7 Trial

Cited by 17 publications

References 19 publications

Cost-effectiveness analysis of axicabtagene ciloleucel as a second-line treatment for diffuse large B-cell lymphoma in China and the United States

Cost-effectiveness analysis of axicabtagene ciloleucel as a second-line treatment for diffuse large B-cell lymphoma in China and the United States

Cost-effectiveness of Axicabtagene Ciloleucel and Tisagenlecleucel as Second-line or Later Therapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Cholesterol efflux from C1QB-expressing macrophages is associated with resistance to chimeric antigen receptor T cell therapy in primary refractory diffuse large B cell lymphoma

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