An updated cost-effectiveness analysis of axicabtagene ciloleucel in second-line large B-cell lymphoma patients in the United States

Abstract

Aims

This economic evaluation of axicabtagene ciloleucel (axi-cel) versus previous standard of care (SOC; salvage chemotherapy followed by high-dose therapy with autologous stem cell rescue) in the second line (2L) large B-cell lymphoma population is an update of previous economic models that contained immature survival data.

Methods

This analysis is based on primary overall survival (OS) ZUMA-7 clinical trial data (median follow-up of 47.2 months), from a United States (US) payer perspective, with a model time horizon of 50 years. Mixture cure models were used to extrapolate updated survival data; subsequent treatment data and costs were updated. Patients who remained in the event-free survival state by 5 years were assumed to have achieved long-term remission and not require subsequent treatment.

Results

Substantial survival and quality of life benefits were observed despite 57% of patients in the SOC arm receiving subsequent cellular therapy: median model-projected (ZUMA-7 trial Kaplan–Meier estimated) OS was 78 months (median not reached) for axi-cel versus 25 months (31 months) for SOC, resulting in incremental quality-adjusted life year (QALY) difference of 1.63 in favor of axi-cel. Incrementally higher subsequent treatment costs were observed in the SOC arm due to substantial crossover to cellular therapies, thus, when considering the generally accepted willingness to pay threshold of $150,000 per QALY in the US, axi-cel was cost-effective with an incremental cost-effectiveness ratio of $98,040 per QALY.

Conclusions

Results remained consistent across a wide range of sensitivity and scenario analysis, including a crossover adjusted analysis, suggesting that the mature OS data has significantly reduced the uncertainty of axi-cel’s cost-effectiveness in the 2L setting in the US. Deferring treatment with CAR T therapies after attempting a path to transplant may result in excess mortality, lower quality of life and would be an inefficient use of resources relative to 2L axi-cel.

Keywords:

• Axicabtagene ciloleucel
• CAR T-cell therapy
• cost-effectiveness
• lymphoma
• mixture cure model
• survival analysis

JEL CLASSIFICATION CODES:

• I19
• I1
• I
• C59
• C5
• C

Transparency

Declaration of financial/other interests

OO reports consultancy and advisory board work with Pfizer, Kite, Gilead, AbbVie, Janssen, TGR therapeutics, ADC, Novartis, Epizyme, Curio science, Nektar, Cargo, Caribou and has received institution funding from Kite, Pfizer, Daichi Sankyo, Allogene and honoraria from Pfizer and Gilead. ARP, SV, and CF are employees of Kite, a Gilead company and have stock ownership. NJS and RB are employees of Maple Health Group, who received fees from Gilead Consulting for the conduct of this work. MD reports honoraria from Roche, Amgen, MSD, Janssen, Bristol-Myers Squibb, Novartis, Gilead Sciences and Abbie; he has received consulting fee or has played an advisory role for Novartis, Bristol-Myers Squibb, Gilead Sciences, Janssen, Abbvie and Genmab. MD has received institutional research support from Novartis, Roche, Takeda, Celgene, MSD, Abbvie, and Lilly. PJ has nothing to disclose. MAP reports honoraria from Adicet, Allogene, Allovir, Caribou Biosciences, Celgene, Bristol-Myers Squibb, Equilium, Exevir, ImmPACT Bio, Incyte, Karyopharm, Kite/Gilead, Merck, Miltenyi Biotec, MorphoSys, Nektar Therapeutics, Novartis, Omeros, OrcaBio, Syncopation, VectivBio AG, and Vor Biopharma. He serves on DSMBs for Cidara Therapeutics, Medigene, and Sellas Life Sciences, and the scientific advisory board of NexImmune. MAP has ownership interests in NexImmune, Omeros and OrcaBio; he has received institutional research support for clinical trials from Allogene, Incyte, Kite/Gilead, Miltenyi Biotec, Nektar Therapeutics, and Novartis.

Author contributions

AP, CF, NJS conceived and designed the analysis. AP, SV, and CF collected the data. RB and NJS performed the analysis. OO, MAP, MD and JP contributed to the interpretation of the analysis. AP, CF and NJS wrote the first draft of the manuscript. All authors provided feedback on the manuscript and all authors approved the final version of the manuscript.

Acknowledgements

The authors would like to thank Lianne Barnieh, of the Maple Health Group, for her contributions to the preparation of this manuscript.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they received consultant fees from Gilead srl. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose. All peer reviewers on this manuscript have received an honorarium from JME for their review work but have no other relevant financial relationships to disclose.

Additional information

Funding

This research was supported in part by NIH/NCI Cancer Center Support Grant P30 CA008748 (MAP). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work received funding from Gilead Sciences.