Dataset Information

Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial.

ABSTRACT: Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy compared to standard of care as second-line therapy in patients with high-risk relapsed/refractory (R/R) large B cell lymphoma (LBCL) considered eligible for autologous stem cell transplantation (ASCT); however, in clinical practice, roughly half of patients with R/R LBCL are deemed unsuitable candidates for ASCT. The efficacy of axi-cel remains to be ascertained in transplant-ineligible patients. ALYCANTE, an open-label, phase 2 study, evaluated axi-cel as a second-line therapy in 62 patients with R/R LBCL who were considered ineligible for ASCT. The primary end point was investigator-assessed complete metabolic response at 3 months from the axi-cel infusion. Key secondary end points included progression-free survival, overall survival and safety. The study met its primary end point with a complete metabolic response of 71.0% (95% confidence interval, 58.1-81.8%) at 3 months. With a median follow-up of 12.0 months (range, 2.1-17.9), median progression-free survival was 11.8 months (95% confidence interval, 8.4-not reached) and overall survival was not reached. There was no unexpected toxicity. Grade 3-4 cytokine release syndrome and neurologic events occurred in 8.1% and 14.5% of patients, respectively. These results support axi-cel as second-line therapy in patients with R/R LBCL ineligible for ASCT. ClinicalTrials.gov Identifier: NCT04531046 .

SUBMITTER: Houot R

PROVIDER: S-EPMC10579056 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial.

Houot Roch R Bachy Emmanuel E Cartron Guillaume G Gros François-Xavier FX Morschhauser Franck F Oberic Lucie L Gastinne Thomas T Feugier Pierre P Duléry Rémy R Thieblemont Catherine C Joris Magalie M Jardin Fabrice F Choquet Sylvain S Casasnovas Olivier O Brisou Gabriel G Cheminant Morgane M Bay Jacques-Olivier JO Gutierrez Francisco Llamas FL Menard Cédric C Tarte Karin K Delfau Marie-Hélène MH Portugues Cédric C Itti Emmanuel E Palard-Novello Xavier X Blanc-Durand Paul P Al Tabaa Yassine Y Bailly Clément C Laurent Camille C Lemonnier François F

Nature medicine 20230914 10

Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy compared to standard of care as second-line therapy in patients with high-risk relapsed/refractory (R/R) large B cell lymphoma (LBCL) considered eligible for autologous stem cell transplantation (ASCT); however, in clinical practice, roughly half of patients with R/R LBCL are deemed unsuitable candidates for ASCT. The efficacy of axi-cel remains to be ascertained in transplant-ineligible patients. ALYCANTE, an open-label, phase 2 s ...[more]

PMID: 37710005

Similar Datasets

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.

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.

Project description:BackgroundIn a phase 1 trial, axicabtagene ciloleucel (axi-cel), an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, showed efficacy in patients with refractory large B-cell lymphoma after the failure of conventional therapy.MethodsIn this multicenter, phase 2 trial, we enrolled 111 patients with diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, or transformed follicular lymphoma who had refractory disease despite undergoing recommended prior therapy. Patients received a target dose of 2×106 anti-CD19 CAR T cells per kilogram of body weight after receiving a conditioning regimen of low-dose cyclophosphamide and fludarabine. The primary end point was the rate of objective response (calculated as the combined rates of complete response and partial response). Secondary end points included overall survival, safety, and biomarker assessments.ResultsAmong the 111 patients who were enrolled, axi-cel was successfully manufactured for 110 (99%) and administered to 101 (91%). The objective response rate was 82%, and the complete response rate was 54%.With a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a complete response. The overall rate of survival at 18 months was 52%. The most common adverse events of grade 3 or higher during treatment were neutropenia (in 78% of the patients), anemia (in 43%), and thrombocytopenia (in 38%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 13% and 28% of the patients, respectively. Three of the patients died during treatment. Higher CAR T-cell levels in blood were associated with response.ConclusionsIn this multicenter study, patients with refractory large B-cell lymphoma who received CAR T-cell therapy with axi-cel had high levels of durable response, with a safety profile that included myelosuppression, the cytokine release syndrome, and neurologic events. (Funded by Kite Pharma and the Leukemia and Lymphoma Society Therapy Acceleration Program; ZUMA-1 ClinicalTrials.gov number, NCT02348216 .).

Project description:BackgroundAxicabtagene 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.ObjectivesTo 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).DesignCost effectiveness analysis of Axi-cel in the treatment of relapsed or refractory large B-cell lymphoma (LBCL).MethodsBased 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.ResultsIn 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.ConclusionAxi-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.

Dataset Information

Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial.

Publications

Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets