Second-Line Chimeric Antigen Receptor T-Cell Therapy in Diffuse Large B-Cell Lymphoma : A Cost-Effectiveness Analysis
Amar H Kelkar1, Edward R Scheffer Cliff2, Caron A Jacobson3
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston; Harvard Medical School, Boston; and Harvard T.H. Chan School of Public Health, Boston, Massachusetts (A.H.K.).
Background:
First-line treatment of diffuse large B-cell lymphoma (DLBCL) achieves durable remission in approximately 60% of patients. In relapsed or refractory disease, only about 20% achieve durable remission with salvage chemoimmunotherapy and consolidative autologous stem cell transplantation (ASCT). The ZUMA-7 (axicabtagene ciloleucel [axi-cel]) and TRANSFORM (lisocabtagene maraleucel [liso-cel]) trials demonstrated superior event-free survival (and, in ZUMA-7, overall survival) in primary-refractory or early-relapsed (high-risk) DLBCL with chimeric antigen receptor T-cell therapy (CAR-T) compared with salvage chemoimmunotherapy and consolidative ASCT; however, list prices for CAR-T exceed $400 000 per infusion.
Objective:
To determine the cost-effectiveness of second-line CAR-T versus salvage chemoimmunotherapy and consolidative ASCT.
Design:
State-transition microsimulation model.
Data Sources:
ZUMA-7, TRANSFORM, other trials, and observational data.
Target Population:
"High-risk" patients with DLBCL.
Time Horizon:
Lifetime.
Perspective:
Health care sector.
Intervention:
Axi-cel or liso-cel versus ASCT.
Outcome Measures:
Incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (iNMB) in 2022 U.S. dollars per quality-adjusted life-year (QALY) for a willingness-to-pay (WTP) threshold of $200 000 per QALY.
Results Of Base-Case Analysis:
The increase in median overall survival was 4 months for axi-cel and 1 month for liso-cel. For axi-cel, the ICER was $684 225 per QALY and the iNMB was -$107 642. For liso-cel, the ICER was $1 171 909 per QALY and the iNMB was -$102 477.
Results Of Sensitivity Analysis:
To be cost-effective with a WTP of $200 000, the cost of CAR-T would have to be reduced to $321 123 for axi-cel and $313 730 for liso-cel. Implementation in high-risk patients would increase U.S. health care spending by approximately $6.8 billion over a 5-year period.
Limitation:
Differences in preinfusion bridging therapies precluded cross-trial comparisons.
Conclusion:
Neither second-line axi-cel nor liso-cel was cost-effective at a WTP of $200 000 per QALY. Clinical outcomes improved incrementally, but costs of CAR-T must be lowered substantially to enable cost-effectiveness.
Primary Funding Source:
No research-specific funding.
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