BACKGROUND: Axicabtagene ciloleucel (axi-cel) is a CD19-directed chimeric antigenic receptor (CAR) T-cell therapy which has been approved by FDA for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (RR-LBCL) after two or more lines of systemic therapy based on the results of the pivotal ZUMA-1 trial: the study demonstrated an objective response rate of 82% and a median overall survival has not been reached after at least 12 months of follow-up (Neelapu et al. 2017), while, historically, median survival of RR-LBCL is 6.3 months (Crump et al. 2017).

AIMS & METHODS: To better understand the economic and health outcome implications of axi-cel in the perspective of the Italian National Healthcare Service, we adapted an earlier US model (Roth et al. 2018) to a Markov decision model assessing lifetime costs and outcomes of RR-LBCL patients treated with axi-cel or best supportive chemotherapy (BSC). Transition probabilities were derived from ZUMA-1 and SCHOLAR-1 studies. Long-term survival of axi-cel treated patients was derived from a mixture cure model (Bansal et al.2018) and Italian life tables. Health utility data were based on published literature (Lin et al. 2018, Chen et al. 2017). Unit costs for chemo-immunotherapy, leukapheresis, adverse events (including ICU stay and tocilizumab use for cytokine releasing syndrome) and stem cell transplant were based on Italian national charges. Costs of palliative care for progressing patients were from a country-specific study (Caroni et al. 2007). Since Axi-cel is not available in Italy yet, the US list price was used and converted in Euros (€327,000). Life years, quality-adjusted life years (QALYs) and costs were generated both with and without discount (3% per year). Uncertainty analysis included one-way and probabilistic sensitivity analysis of all model inputs.

RESULTS: Over a lifetime horizon, treatment with axi-cel increased life expectancy of RR-LBCL by 6.64 QALYs (9.45 undiscounted) at an additional cost of €297,114 (€291,245 undiscounted): the corresponding cost per QALY gained was €44,746 (undiscounted €30,819). Details are reported in the table below. The cost-effectiveness of axi-cel was most sensitive to the axi-cel price, the proportion of long-term remission after axi-cel and the time horizon. Probabilistic sensitivity analysis showed 67% (95% undiscounted) likelihood of axi-cel being cost-effective at a willingness to pay threshold of €50,000/QALY.

DISCUSSION: Axi-cel may be considered a cost-effective alternative to salvage chemotherapy for adults with RR-DLBCL from an Italian third-party payer perspective. This analysis confirms the good value for money of axi-cel, which has been previously reported in a US-specific analysis (Roth et al. 2018). Since follow-up data are limited for patients treated with axi-cel, continued evaluation of outcomes and costs are necessary to better understand the value of this novel therapy over years of patient experience.

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Disclosures

Marchetti:Gilead: Consultancy; takeda: Speakers Bureau; amgen: Speakers Bureau; janssen: Speakers Bureau. Martelli:Gilead: Employment. Zinzani:Bayer: Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau.

Topics:
axicabtagene ciloleucel, b-lymphocytes, cost effectiveness, italy, lymphoma, chemotherapy regimen, follow-up, abnormal involuntary movement scale, adverse event, alberta infant motor scales

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2018 by The American Society of Hematology
2018
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