NICE Recommends Axicabtagene Ciloleucel for Lymphoma

John Stewart, of NHS England

The United Kingdom’s National Institute for Health and Care Excellence (NICE) has issued draft guidance supporting the use of axicabtagene ciloleucel (axi-cel; Yescarta) for adults with diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) following at least 2 previous lines of systemic therapy.¹ This decision makes the anti-CD19 CAR T-cell agent available for approximately 450 people in the UK.

This marks the first time NICE has supported personalized immunotherapy for lymphoma.

“Five years ago, the NHS [National Health Service] led the way in Europe by striking commercial deals for revolutionary CAR-T cancer treatment and today we have used our commercial capabilities to reach a deal that secures long-term patient access to this personalized therapy,” NHS director of specialized commissioning and interim commercial medicines director John Stewart said in a news release. “This advanced therapy has been commissioned through the Cancer Drugs Fund since 2018, allowing evidence to be collected that confirms its benefits for patients facing this aggressive form of lymphoma and now enables the NHS to provide routine access at a fair price for taxpayers.”

There is currently no standard treatment for relapsed/refractory DLBCL or PMBCL. Best supportive care usually includes salvage chemotherapy. An estimated 5500 people are diagnosed with DLBCL in the UK. It is an aggressive disease which progresses quickly and is the most common type of high-grade non-Hodgkin lymphoma (NHL). It can develop at any age, but most patients are aged 65 years or older at diagnosis.

The list price for axi-cel is £280,451 ($347,240.80) per each 68 ml single-infusion bag. Kite Pharmaceuticals has agreed to make the drug available to the NHS for an undisclosed discount.²

NICE based its recommendation on data from the multicenter, phase 2 ZUMA-1 trial (NCT02348216) of 111 patients with relapsed/refractory DLBCL, PMBCL, or transformed follicular lymphoma (FL). Most patients (91%) received an infusion of 2×106 CAR T cells.

The FDA approved axi-cel in this patient population in October 2017.³

Axi-cel induced an objective response rate (ORR) of 82% with a complete response (CR) rate of 54%. At a median follow-up of 15.4 months, 42% of the patients continued to have a response, with 40% continuing to have a CR. The 18-month overall survival (OS) rate was 52%.⁴

The FDA approved axi-cel for patients with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or relapses within 12 months of first-line chemoimmunotherapy in April 2022. The regulatory decision was based on findings from the phase 3 ZUMA-7 trial (NCT03391466), which showed that at a median follow-up of 24.9 months, the estimated median event-free survival (EFS) with the CAR T-cell therapy was 8.3 months (95% CI, 4.5-15.8) vs 2.0 months (95% CI, 1.6-2.8) with standard-of-care (SOC) treatment (HR, 0.40; 95% CI, 0.31-0.51; P <.0001).⁵

The estimated 18-month EFS rates in the investigative and control arms were 41.5% (95% CI, 34.2%-48.6%) and 17.0% (95% CI, 11.8%-23.0%), respectively.

In December 2022, Japan’s Ministry of Health, Labor and Welfare (MHLW) approved axi-cel for the initial treatment of patients with relapsed/refractory LBCL including DLBCL, PMBCL, transformed FL, and high-grade B-cell lymphoma based on data from ZUMA-7.⁶

References

1. More than 400 people set to benefit after NICE approves ground-breaking CAR-T therapy to treat aggressive form of blood cancer. News release. NICE. January 26, 2023. Accessed January 30, 2023. https://bit.ly/3HEPjz4
2. Axicabtagene ciloleucel for treating diffuse large B-cell lymphoma and primary mediastinal large B-cell lymphoma after 2 or more systemic therapies. Final appraisal document. January 2023. Accessed January 30, 2023. https://bit.ly/3JuyGr0
3. FDA approves axicabtagene ciloleucel for large B-cell lymphoma. News release. FDA. October 25, 2017. Accessed January 30, 2023. https://bit.ly/3F8EzFE
4. Neelapu SS, Locke FL, Bartlett NL, et al. Axicabtagene ciloleucel CAR T-cell therapy in refractory large b-cell lymphoma. N Engl J Med. 2017;377(26):2531-2544. doi:10.1056/NEJMoa1707447
5. FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma. News release. FDA. April 1, 2022. Accessed January 30, 2023. https://bit.ly/3iSQ8XT
6. Yescarta® now approved in Japan for initial treatment of relapsed/refractory large B-cell lymphoma. News release. Kite. December 22, 2022. Accessed January 30, 2023. https://bit.ly/3FQTQMt