Study Suggests Second-line Axi-Cel Is Cost-effective vs Standard Care in R/R DLBCL

The chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel (axi-cel) may be cost-effective in the second-line setting or later compared with the standard of care in relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL), according to a study published in JAMA Network Open.¹ The findings also suggest that another CAR T-cell therapy, tisagenlecleucel (tisa-cel), is more cost-effective than the standard of care in the third line or later.

CAR T-cell therapies such as axi-cel and tisa-cel are approved for the treatment of B-cell malignancies in patients who are refractory or relapsed after 2 or more lines of standard-of-care therapy. Although they come with high price tags, previous studies have shown incremental survival gains and cost-effectiveness ratios with third-line or later CAR T-cell therapy, the authors noted.

The label for axi-cel was expanded to include second-line treatment for patients with DLBCL in light of results from the ZUMA-7 (NCT03391466) trial showing a 65% complete response (CR) rate with axi-cel vs 32% with the standard of care in the second line.² In the BELINDA trial (NCT03570892), tisa-cel showed similar efficacy to the standard of care in terms of CR rates in the second line.³ As these and more results are published, the authors noted, utilization of CAR T-cell therapies, reimbursement policies, and insurance coverage may be impacted.

The study performed cost-effectiveness analyses on axi-cel and tisa-cel compared with salvage chemotherapy followed by hematopoietic stem cell transplantation (HSCT) for patients with relapsed or refractory DLBCL in the second line or later, assessing cost from the US health care sector and societal standpoints.

Data from the ZUMA-7 and BELINDA trials were used to form the cost-effectiveness models in the study. In these trials, patients whose disease did not respond to standard treatment were given CAR T-cell therapy. A separate scenario analysis compared axi-cel with standard treatment in the second line and did not include treatment crossover to CAR T cells.

Researchers used a partitioned survival model with 2021 US$ and quality-adjusted life-years (QALYs) over a lifetime, setting a cost-effectiveness threshold of $150,000 per QALY. Incremental cost-effectiveness ratios (ICERs) both for the health care sector and societal standpoint were determined from costs and QALYs that were discounted at 3% annually.

Patients in the second-line axi-cel cohort had incremental survival benefits of 0.60 QALYs vs the standard of care. From the health care sector perspective, axi-cel in the second-line setting showed an ICER of $99,101 per QALY; from a societal perspective, it was associated with an ICER of $97,977 per QALY in the second line. Standard salvage chemotherapy followed by HSCT outperformed tisa-cel in the second line, which was associated with survival of -0.02 QALYS and incremental costs of $37,803 from the health care sector standpoint and $39,480 from the societal perspective.

Patients given tisa-cel in the third line or later experienced incremental survival benefits of 2.14 QALYs, with an ICER of $126,593 per QALY from the health sector perspective and $128,012 per QALY from a societal standpoint.

The scenario analysis of second-line axi-cel with no treatment switching showed an ICER of $216,790 per QALY compared with standard care from a health care sector view. From a societal perspective, axi-cel was associated with an ICER of $218,907 per QALY compared with the standard of care in the second line. In another scenario analysis factoring in patients who experienced long-term progression-free survival and would not accrue additional costs related to disease progression, the ICERs dropped to $125,962 per QALY and $122,931 per QALY from the health care sector and societal perspectives, respectively.

The findings support that axi-cel is cost-effective in the second line setting for patients with R/R DLBCL based on a willingness-to-pay threshold of $150,000 per QALY, and tisa-cel is cost-effective in the third line or later based on the same threshold.

“Nevertheless, the probabilistic sensitivity analysis demonstrated a 57% probability that axicabtagene ciloleucel would be cost-effective at this threshold,” the authors wrote. “Our probabilistic sensitivity analysis at the current list price for commercial CAR T-cell therapy reflects the value of conducting research to identify patients who can achieve the best clinical outcomes or explore alternative pricing models for CAR T-cell therapy.”

Reference

1. Choe JH, Abdel-Azim H, Padula WV, Abou-El-Enein M. Cost-effectiveness of axicabtagene ciloleucel and tisagenlecleucel as second-line or later therapy in relapsed or refractory diffuse large B-cell lymphoma. JAMA Netw Open. 2022;5(12):e2245956. doi:10.1001/jamanetworkopen.2022.45956

2. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133

3. Bishop MR, Dickinson M, Purtill D, et al. Second-line tisagenlecleucel or standard care in aggressive B-cell lymphoma. N Engl J Med. 2022;386(7):629-639. doi:10.1056/NEJMoa2116596