Cost-effectiveness of axicabtagene ciloleucel versus lisocabtagene maraleucel for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy in the US

Abstract

Aims

This study evaluated from a US payer perspective the cost-effectiveness of two chimeric antigen receptor T (CAR T) cell therapies, axicabtagene ciloleucel (axi-cel) versus lisocabtagene maraleucel (liso-cel), for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma (LBCL) following two or more systemic therapy lines.

Methods

We developed a 3-state (i.e., pre-progression, post-progression, death) partitioned survival model to estimate patients’ lifetime outcomes. Mixture cure models were used for survival extrapolation to account for long-term remission. Survival inputs were based on a matching-adjusted indirect comparison (MAIC) that reweighted the ZUMA-1 population (receiving axi-cel) to match patient characteristics in TRANSCEND-NHL-001 (assessing liso-cel). Costs included apheresis, drug acquisition, and administration for conditioning chemotherapy and CAR T therapies, monitoring, transplant, hospitalization, adverse events, routine care, and terminal care, per published literature and databases. Utilities were derived from ZUMA-1 and literature. Deterministic and probabilistic sensitivity analyses were conducted.

Results

In the base case, axi-cel was associated with more QALYs (7.76 vs. 5.94) and greater costs overall ($611,440 vs. $597,174) than liso-cel, at $7,843/QALY gained. The incremental costs (+$14,266) were largely driven by higher routine care costs (+$18,596) due to longer survival and hospitalization (+$10,993) but partially offset by reduced costs of CAR T acquisition (‒$11,300) and terminal care (‒$4,025). Sensitivity analyses consistently suggested robustness of base-case results.

Limitations

This study relied on an MAIC in which trial design differences and unobserved confounders could not be accounted for. Future real-world studies for recently approved CAR T are warranted to validate our results. Due to a lack of data, we assumed equivalent use of transplants and treatment for B-cell aplasia between the two therapies based on clinicians’ opinions.

Conclusions

In the US, axi-cel is a potentially cost-effective treatment option compared with liso-cel for adult patients with r/r LBCL after two or more systemic therapy lines.

Keywords:

• Cost-effectiveness
• large B-cell lymphoma
• anti-CD19 chimeric antigen receptor T-cell
• axicabtagene ciloleucel (axi-cel)
• lisocabtagene maraleucel (liso-cel)
• mixture cure model
• survival analysis
• matching-adjusted indirect comparison
• quality-adjusted life years

JEL CLASSIFICATION CODES:

• C01
• C
• O51
• O5
• O

Transparency

Declaration of funding

The design and conduct of this study and manuscript development were funded by Kite, A Gilead Company.

Declaration of financial/other interests

Frederick L. Locke: Scientific Advisory Role: Allogene, Amgen, Bluebird Bio, BMS/Celgene, Calibr, Cellular Biomedicine Group, GammaDelta Therapeutics, Iovance, Kite Pharma, Janssen, Legend Biotech, Novartis, Sana, Takeda, Wugen, Umoja; Research Funding: Kite Pharma (Institutional), Allogene (Institutional), Novartis (Institutional), BlueBird Bio (Institutional), BMS (Institutional), National Cancer Institute, Leukemia and Lymphoma Society; Patents, Royalties, Other Intellectual Property: Several patents held by the institution in my name (unlicensed) in the field of cellular immunotherapy; Consulting Role: Cowen, EcoR1, Emerging Therapy Solutions, Gerson Lehrman Group (GLG); Education or Editorial Activity: Aptitude Health, ASH, BioPharma Communications CARE Education, Clinical Care Options Oncology, Imedex, Society for Immunotherapy of Cancer.

Rongzhe Liu, Ibrahim Diakite, and Iman Nourhussein are employees of OPEN Health that received funding from Kite, A Gilead Company to conduct the study.

Julia Thornton Snider, Chaoling Feng, and Anik Patel are employees of Kite, A Gilead Company and hold Gilead equity.

Olalekan O. Oluwole has served as a compensated scientific advisor to Kite, Pfizer, Spectrum, Bayer, Legend, Janssen, and Curio Science.

Peer reviewers on this manuscript have received an honorarium from JME for their review work but have no other relevant financial relationships to disclose.

Acknowledgements

The authors thank Christina DuVernay, an employee of OPEN Health, Bethesda, MD, for editorial assistance with the manuscript. The authors thank Anna Purdum, an employee of Kite, A Gilead Company, Santa Monica, CA, for review of the manuscript.

Previous presentations

Not applicable.