Chimeric antigen receptor T-cell (CAR-T) therapy may be a cost effective approach for the treatment of adults with diffuse large B-cell lymphoma (DLBCL), depending on the long-term outcomes of these patients. Findings from a study published in the Journal of Clinical Oncology have shown.

Diffuse large B-cell lymphoma is the most common subtype of lymphoma, with approximately two-thirds of patients achieving long-term remission following first-line treatment with chemoimmunotherapy. Tisagenlecleucel and axicabtagene ciloleucel are 2 potentially curative anti-CD19 CAR-T therapies approved for the treatment of relapsed/refractory DLBCL in adult patients who have received 2 or more lines of systemic therapy; these CAR-T therapies have also been studied in the setting of relapse after hematopoietic stem cell transplantation (HSCT) in patients with this disease. 2,3

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As the cost of both of these CAR-T cell therapies is very high, their cost-effectiveness is an important factor for consideration when weighing treatment decisions for these patients. Another option for patients with relapsed/refractory DLBCL is salvage chemoimmunotherapy, often followed by HSCT in those achieving a response to treatment.

In this study, the cost effectiveness of each of the CAR-T therapies was independently compared with the cost effectiveness of a mix of 4 standard regimens of salvage chemoimmunotherapy plus HSCT in a fraction of patients achieving a response to treatment using models based on data from large randomized clinical trials of patients with relapsed/refractory DLBCL. The 2 CAR-T therapies were not directly compared due to a lack of data from head-to-head randomized trials. Mean life expectancies associated with the different treatments were assessed based on rates of 5-year progression-free survival (PFS). Patient outcome measures used in this study included life years, lifetime costs, quality-adjusted life years (QALYs), and incremental cost per QALY gained.

Patients treated with axicabtagene ciloleucel had mean life expectancies of 11.8 years, 10.0 years, and 9.1 years with 5-year PFS rates of 40%, 30% and 20%, respectively. Those treated with tisagenlecleucel had mean life expectancies of 8.3 years, 7.0 years, and 5.90 years with 5-year PFS rates of 35%, 25%, and 15%, respectively. For comparison, the mean life expectancy of patients treated with salvage chemoimmunotherapy was 3.7 years.

The costs associated with these treatments were $638,000 to $655,000 for axicabtagene ciloleucel; $521,000 to $529,000 for tisagenlecleucel; and $145,000 to $195,000 for salvage chemoimmunotherapy.

“At current prices, the cost effectiveness of axicabtagene ciloleucel and tisagenlecleucel were dependent on their long-term outcomes,” the study authors noted.

For example, patients treated with axicabtagene ciloleucel with an associated 5-year PFS rate of 40% had an additional 3.72 QALYs at a cost of $129,000/QALY gained compared with salvage chemoimmunotherapy. When the 5-year PFS rates was 30% these values dropped to 2.96 QALYs at a cost of $159,000/QALY. Similarly, for patients treated with tisagenlecleucel compared with salvage chemoimmunotherapy, an additional 2.14 QALYs at a cost of $168,000 were gained when the 5-year PFS rate was 35%, dropping to 1.58 QALYs at a cost of $223,000 when the associated 5-year PFS rate was 25%.

Both CAR-T therapies meet a less than $150,000/QALY threshold, at 2018 prices. However, this depends on long-term outcomes compared with chemoimmunotherapy and HSCT, which are uncertain. Widespread adoption would substantially increase healthcare costs for treating non-Hodgkin lymphoma, the study authors noted. “Price reductions or payment for initial response would improve cost effectiveness, even with modest long-term outcomes,” they concluded.

References

1. Lin JK, Muffly LS, Spinner MA, et al. Cost effectiveness of chimeric antigen receptor T-cell therapy in multiply relapsed or refractory adult large B-cell lymphoma [published online June 3, 2019]. J Clin Oncol. doi: 10.1200/JCO.18.02079

2. Kymriah™ [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018.

3. Yescarta® [package insert]. Santa Monica, CA: Kite Pharma Inc; 2019.