Brexucabtagene Autoleucel May Be a Cost-Effective Treatment for Relapsed/Refractory MCL

Brexucabtagene autoleucel ( Brexu-cel; Tecartus) as a treatment for patients with relapsed/refractory mantle cell lymphoma (MCL) following a Bruton tyrosine kinase inhibitor (BTKi) appears to be a cost-effective option vs best supportive care.¹

Brexu-cel treatment yielded large incremental gains in life years and quality-adjusted life years (QALY) that resulted in a base case incremental cost-utility ratio of $88,503 per QALYs gained. The CAR T-cell therapy could be an affordable treatment option for those who have already received a BTKi in Canada.

“The limitations of this study include absence of [randomized controlled trial] data for [brexu-cel] vs [best supportive care], lack of inclusion or subsequent therapies due to data limitations, and immaturity of the underlying survival data,” investigators of the study wrote.

The main objective of the trial was to assess the cost-effectiveness of brexu-cel vs best supportive care from a Canadian public payer perspective. Currently, there is no standard of care treatment for patients with relapsed/refractory MCL following a BTKi treatment.

The analysis included patients who participated in the phase 2 ZUMA-2 (NCT02601313), which assessed the use of brexu-cel in patients with relapsed/refractory MCL.² Investigators used a partitioned-survival mixture-cure model was used to account for patients in the trial who achieved long-term remissions.

Estimates for overall survival and progression-free survival were based on the ZUMA-2 trial findings. The median follow-up was 12.3 months. OS and PFS data for those who received best supportive care was pulled from a literature-based meta-analysis of treatments used in the treatment of relapsed/refractory MCL. Cost categories from the trial included conditioning chemotherapy, drug acquisition, bridging therapy, stem cell transplant, adverse effects, routine disease management, hospitalization, apheresis, and end-of-life costs.

In the base case analysis over a lifetime horizon, brexu-cel yielded 13.22 undiscounted life-years vs 1.76 for best supportive care. Additionally, brexu-cel arm yielded 8.34 discounted quality-adjusted life-years vs 1.31 years with best supportive care.

The total discounted costs associated with the brexu-cel arm was $688,040 vs $66,108 in the best supportive care arm. Findings from the analysis were robust and sensitive to changes in duration of non-ICU hospitalizations, with a certain patients requiring hospitalization for progressive disease.

A total of 105 patients enrolled on the ZUMA-2 trial who were treated a conditioning regimen consisting of 30 mg/m² of fludarabine and 500 mg/m² of cyclophosphamide followed by brexu-cel at 2 x ¹⁰⁶ or axicabtagene ciloleucel (Yescarta) at 2 x ¹⁰⁶. The primary end point was objective response by independent radiology review committee. Secondary end points included duration of response, best objective response, and PFS.

To be eligible for the study, patients needed to have received 5 prior regimens for MCL, including an anthracycline- or bendamustine-containing chemotherapy agent, an anti-CD20 monoclonal antibody, and ibrutinib (Imbruvica) or acalabrutinib. Moreover, patients needed to have at least 1 measurable lesion, creatinine clearance, cardiac ejection fraction of 50% or more, and baseline oxygen saturation of over 92%. Exclusion criteria included a known history of infection with human immunodeficiency virus or hepatitis B or C, seizure disorder, or presence of a fungal, bacteria, or viral infection.

These cost-effectiveness findings were presented at the 2022 Tandem Meeting.

References

1. Seftel, Lemieux C, Cameron D, et al. Cost-effectiveness of brexucabtagene autoleucel versus best supportive care for the treatment of relapsed/refractory mantle cell lymphoma following treatment with a Bruton’s tyrosine kinase inhibitor in Canada. Presented at the 2022 Tandem Meeting; April 23-26, 2022. Poster 423.
2. Wang M, Munoz J, Goy A, et al. KTE-X19 CAR T-cell therapy in relapsed or refractory mantle-cell lymphoma. N Engl J Med. 2020;382(14):1331-1342. doi:10.1056/NEJMoa1914347