CAR-T’s ‘significant clinical benefits’ come at a ‘disproportionately high’ price
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Chimeric antigen receptor T cells have improved survival rates as second-line therapy for individuals with high-risk diffuse large B-cell lymphoma, but available therapies lack cost-effectiveness at current prices, study results showed.
The analysis — published in Annals of Internal Medicine — revealed that CAR-T increased OS by 1 to 4 months compared with the standard salvage chemoimmunotherapy and consolidative autologous stem cell transplantation (ASCT). At a cost of more than $400,000 per infusion, the benefits of CAR-T do not outweigh the higher prices, researchers concluded.
“While axi-cel and liso-cel clearly offer significant clinical benefits, the disproportionately high costs compared with marginal improvement in efficacy could limit the availability of these therapies in patients who may benefit the most, underscoring the need for a balance between innovation and affordability,” Amar H. Kelkar, MD, MPH, a stem cell transplantation physician in the department of medical oncology at Dana-Farber Cancer Institute, told Healio.
Background and methodology
Approximately 150,000 new cases of diffuse large B-cell lymphoma occur each year, and about 60% of those patients had long-term PFS with a first-line treatment of chemoimmunotherapy. However, only about 20% of patients who relapsed or developed refractory disease experienced remission with chemoimmunotherapy and consolidative ASCT.
CAR-T showed long-term remission as second-line therapy in roughly 40% of patients. The FDA approved axicabtagene ciloleucel (also called axi-cel; Yescarta, Kite Pharma/Gilead Sciences), tisagenlecleucel (also called tisa-cel; Kymriah, Novartis), and lisocabtagene maraleucel (also called liso-cel; Breyanzi, Bristol Myers Squibb) for third- or subsequent-line treatment.
“High-risk” patients who had refractory disease to first-line treatment or relapsed within a year had better EFS rates on the ZUMA-7 (axi-cel) and TRANSFORM (liso-cel) trials compared with chemoimmunotherapy and consolidative ASCT. ZUMA-7 patients also had better OS numbers.
Kelkar and colleagues used data from multiple trials, including ZUMA-7 and TRANSFORM, to simulate outcomes for 10,000 patients to determine whether axi-cel or liso-cel could be a cost-effective treatment over chemoimmunotherapy and consolidative ASCT.
They measured the incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (iNMB) with a willingness to pay of $200,000 per quality-adjusted life years added.
Results and what’s next
Patients receiving axi-cel had longer median OS than patients receiving chemoimmunotherapy and consolidative ASCT (42 months vs. 38 months) and longer PFS (27 months vs. 17 months).
Patients receiving liso-cel also had longer median OS than patients receiving chemoimmunotherapy and consolidative ASCT (34 months vs. 33 months) and longer PFS (14 months vs. 9 months).
However, only 19.96% of simulations resulted in axi-cel being cost effective and just 18.98% for liso-cel.
Axi-cel had a base ICER of $684,225 per quality-adjusted life year added with an iNMB of $107,642. Liso-cel produced a base ICER of $1,171,909 per quality-adjusted life year added with an iNMB of $102,477.
Kelkar and colleagues found that axi-cel needed a maximum price of $321,123 with a willingness to pay of $200,000 per quality-adjusted life year to be cost effective. Liso-cel should be priced at $313,730 at the same level.
The cost of axi-cel increased to $418,000 in 2023 and liso-cel jumped to $412,000, according to study investigators.
“We were able to demonstrate that the only change that could make these CAR-T therapies cost-effective was to lower the price below $300,000 per infusion,” Kelkar said.
Prices could feasibly drop with outpatient CAR-T care or the creation of generic treatments. Researchers also theorized there’s room to lower fees based on the current production costs of between $18,000 and $20,000 per infusion.
“It’s vital to emphasize that the goal of such research is not to diminish the scientific triumph that CAR-T therapy represents, but to highlight the necessity for a health care environment where innovation is rewarded yet remains attainable for patients,” Kelkar said. “We need to foster a dialogue among all stakeholders — including manufacturers, health care providers, patients, and policymakers — to work toward sustainable pricing models for these groundbreaking treatments.”
For more information:
Amar H. Kelkar, MD, MPH, can be reached at amarh_kelkar@dfci.harvard.edu.
Perspective
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Craig Sauter, MD
CAR-T directed against CD19 has revolutionized the treatment of relapsed and primary refractory diffuse large B-cell lymphoma, the most common aggressive non-Hodgkin lymphoma. Most recently, both the ZUMA-7 and TRANSFORM studies have reported positive for axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (liso-cel), respectively, supplanting platinum-containing salvage chemoimmunotherapy followed by consolidative high-dose chemotherapy and autologous stem cell transplantation as standard of care for primary refractory or early relapsed DLBCL in the second line of therapy.The analysis by Kelkar and colleagues calls into question the cost-effectiveness of these therapies in the second line. While it is acknowledged that these gene-modified autologous T-cell products are met with an exorbitant cost, determination of cost-effectiveness per the elegant simulation models — considering variables including quality of life, adverse effects and DLBCL effectiveness — by Kelkar and colleagues has inherent arbitrarily defined thresholds. It is accepted that incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit has precedent as a measure of cost-effectiveness. The authors then determined ICER against a generous yet arbitrarily set willingness-to-pay threshold of $200,000 within the United State health care payer mix. The ICER per quality-adjusted life years exceeded these thresholds, thus were deemed not cost-effective for both axi-cel and liso-cel.
Ultimately, these simulated analyses put ‘price-on-life,’ though the authors should be commended for illustrating the excessive price that comes with these novel — and ultimately effective — therapies for patients with this potentially devastating disease. There is clearly a need to make these therapies more cost-effective in the current health care environment.
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