Second-line axicabtagene ciloleucel (axi-cel) is cost-effective in cases of primary refractory or early relapsed and transplant-eligible diffuse large B-cell lymphoma (DLBCL), but the cost-effectiveness of this treatment in the second-line setting depends on long-term outcomes, a study in Blood suggests.
Treatment with chimeric antigen-receptor (CAR) T-cell therapy and transplant are typically only accessible in tertiary centers, and these treatment approaches are often expensive and resource-intensive, explained lead author Swetha Kambhampati, MD, of City of Hope National Medical Center in California.
“It becomes really important to assess cost-effectiveness for treatments,” she added, “particularly given that around one-third of patients end up requiring relapse treatments.”
Researchers used modeling data from the ZUMA-7 study, which included patients with primary refractory or early relapse and who were transplant-eligible. Researchers assessed the cost-effectiveness of second-line CAR T-cell therapy in high-risk DLBCL and conducted a threshold analysis to determine cases in which second-line CAR T-cell therapy could be cost-effective in all patients with relapsed/refractory (R/R) disease.
The researchers developed a Markov model to evaluate the cost-effectiveness of second-line axi-cel compared with standard of care in a simulated cohort of U.S. adults (mean age = 65 years) with primary refractory or early relapsed DLBCL. Using data from ZUMA-7, the investigators estimated survival, including event-free survival (EFS).
According to the analysis, second-line axi-cel was considered cost-effective at a willingness-to-pay (WTP) threshold of $150,000/quality-adjusted life-year (QALY) ($93,547/QALY), assuming a five-year EFS of 35% with axi-cel and 10% with standard of care. Despite this finding, the investigators noted the treatment did not demonstrate cost-effectiveness if the five-year EFS was 26.4% or less or if the treatment cost was more than $972,061 at a WTP threshold of $150,000.
In 73% of 10,000 Monte-Carlo iterations, second-line axi-cel was also considered a cost-effective strategy at a WTP threshold of $150,000. The researchers explained second-line axi-cel is cost-effective compared with standard of care in aggressive R/R DLBCL at WTP thresholds of $150,000/QALY, but this cost-effectiveness was contingent upon whether “the absolute benefit in EFS is maintained over time.”
The researchers added that the regular use of second-line CAR T-cell therapy could add approximately $1.5 billion each year to U.S. health care expenditures if it were used in 65% of patients with DLBCL with primary refractory or early relapse. According to the researchers, this finding highlights “the importance of alternative reimbursement models and other efforts to reduce” treatment costs.
In their discussion, the researchers concluded second-line CAR T-cell therapy remains cost-effective in primary refractory or early relapse DLBCL, despite the substantial costs associated with the therapy, given the suboptimal effectiveness of standard salvage chemoimmunotherapy and autologous stem cell transplant observed in the ZUMA-7 results.
Limitations of the analysis included the modeling of a single CAR T-cell product and the lack of long-term follow-up data from ZUMA-7.
Dr. Kambhampati noted future research should evaluate the safety and efficacy of second-line axi-cel in real-world practice. She suggested that knowledge gained from research on this topic may help further inform the cost-effectiveness of the treatment. There is also a need to perform a cost-effectiveness analysis that compares axi-cel to other products, particularly therapies that have demonstrated survival benefits when used in the second-line setting, she added.
Corresponding author Nikhil Thiruvengadam, MD, of Loma Linda University Health in California, explained there is currently a need to better define how to select treatment in DLBCL, given that many therapies are undergoing approval and several of them come at a substantial cost.
“Every intervention has to be weighed as a trade-off between other interventions,” Dr. Thiruvengadam said. He added that “identifying the highest risk subgroup that derives the most benefit [from axi-cel] long-term and maximizing the cost-effectiveness” are key moving forward.
Any conflicts of interest declared by the authors can be found in the original article.
Reference
Kambhampati S, Saumoy M, Schneider Y, et al. Cost effectiveness of second-line axicabtagene ciloleucel in relapsed refractory diffuse large B-cell lymphoma [published online ahead of print, 2022 Aug 1]. Blood. doi: 10.1182/blood.2022016747.