First CAR T-cell therapy recommended for routine use on the NHS in England

First CAR T-cell therapy recommended for routine use on the NHS in England

- Eligible adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) who have received 2 or more systemic therapies will have long-term NHS access to this treatment -

26^th JANUARY 2023, LONDON, UK – Gilead Sciences Ltd. and Kite, a Gilead company, today announced that the National Institute for Health and Care Excellence (NICE) has recommended Yescarta^®[1] ▼ (axicabtagene ciloleucel; axi-cel) for routine commissioning on the NHS in England for the treatment of some adults with certain forms of lymphoma. Specifically, patients with diffuse large B-cell lymphoma (DLBCL) and primary mediastinal large B-cell lymphoma (PMBCL) who have already been treated with 2 or more systemic therapies may be eligible for treatment. Through the Cancer Drugs Fund, in 2018, England was the first country in Europe to provide access to a chimeric antigen receptor (CAR) T-cell therapy to treat these blood cancers, and since then over 500 patients in England have received axi-cel.

Dr Graham Collins, Consultant Haematologist at Oxford University Hospitals NHS Foundation Trust said: “Since the earliest clinical trial data on CAR T-cell therapies were presented, there has been excitement in the clinical community about their potential to help fight cancer. Today’s news is encouraging as it shows that even in the real-world setting, these therapies are living up to their expectations for patients with aggressive forms of lymphoma. Importantly, it means some patients who have received prior treatment have the potential to face a different outlook on their prognosis.”

CAR T-cell therapy is an individualised treatment for patients that is currently licensed for people living with some types of advanced blood cancer. CAR T-cell therapy engineers a patient’s own immune cells (T-cells) to detect, target and destroy cancer cells.

Dr Véronique Walsh, Vice President and General Manager, Gilead Sciences UK & Ireland said: “We are pleased to announce that, moving forward, axi-cel will be routinely available in the third line setting for all eligible DLBCL and PMBCL patients on the NHS. This news comes at a time when new hospitals are preparing to deliver CAR T-cell therapies, and will mean that healthcare professionals in these centres will have this treatment as an important option for their patients.”

DLBCL and PMBCL are both aggressive forms of non-Hodgkin lymphoma. Around 14,200 cases of non-Hodgkin lymphoma are diagnosed in the UK each year, of which approximately 5,500 are diagnosed with DLBCL and 330 with PMBCL.[1]^,[2],[3] After initial chemotherapy, up to 45% of patients with DLBCL will require a second line treatment, which often involves high dose chemotherapy and a stem cell transplant.[4] Of those who receive a transplant, about 50% will ultimately relapse.[5] This decision ensures that these patients in the third line setting will continue to have access to CAR T-cell therapy.

Overall, survival of DLBCL significantly lags behind the average for all blood cancers, with only 60% of people living with this aggressive form of cancer surviving for 5 years compared to 70% across blood cancers more generally.[6]^,[7]

Helen Rowntree, CEO at Blood Cancer UK said: “CAR-T therapies offer hope to people who are living with the most aggressive forms of blood cancer. For people living with diffuse large B-cell lymphoma, the risk of recurrence and uncertainty about which treatment options will be available to them can add distress at an already very difficult time. We’re pleased that this CAR T-cell therapy can be a viable option for certain blood cancer patients in the long term. It gives people who find themselves in this position more clarity about their treatment options.”

Helen continued “It also demonstrates the benefit of the NHS England’s Cancer Drugs Fund, which led to many accessing this drug in the period of time when NICE was gathering evidence and deliberating on its cost-effectiveness. All in all, it’s good news for people with blood cancer, however we know there’s more work to do, because still too many people are dying of blood cancer.”

NOTES TO EDITORS

About axicabtagene ciloleucel (axi-cel)[8]

Axi-cel is a CD19-directed genetically modified autologous T-cell immunotherapy indicated for the treatment of:

• Adult patients with diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy (note: under review by NICE).
• Adult patients with relapsed or refractory (r/r) DLBCL and primary mediastinal large B-cell lymphoma (PMBCL), after two or more lines of systemic therapy.
• Adult patients with r/r follicular lymphoma (FL) after three or more lines of systemic therapy (note: under review by NICE).

As part of the therapy, T-cells are drawn from a patient’s blood and reprogrammed in a lab to create T-cells that are genetically engineered to kill cancer cells. Axi-cel is administered to the patient via a single intravenous infusion following the administration of a round of chemotherapy designed to accommodate the new cells and minimise the patient’s immune reaction to them.

Axi-cel was investigated in the pivotal ZUMA-1 trial (NCT02348216) of patients with refractory large B-cell lymphoma. In the single-arm trial - a pivotal analysis as assessed by an independent review committee - 72% of patients (n=73/101) who received a single infusion of axi-cel responded to therapy, with 51% (n=52/101) achieving a complete response (CR) with a median follow-up of 15.1 months.⁸

In the five-year follow up analysis of the ZUMA-1 trial, among all patients treated with axi-cel, the five-year OS rate was 42.6% (95% CI, 32.8 – 51.9).[9] Among patients who had a CR, the five-year OS rate was 64.4% (95% CI, 50.8 – 75.1) and median survival time has yet to be reached. Between the 4 and 5 year analysis, 92% of patients remained alive and have received no additional treatment since their one-time infusion of axi-cel.

Axi-cel may cause side effects that are severe or life-threatening, such as cytokine release syndrome (CRS) or neurological toxicities. In ZUMA-1, 11% of patients experienced Grade 3 or higher CRS and 31% experienced Grade 3 or higher neurologic toxicities.⁸ Overall, 98% of patients recovered from CRS and/or neurologic adverse reactions.⁸ Treatment algorithms have been developed to manage some of the symptoms associated with both CRS and neurologic adverse reactions experienced by patients on axi-cel.

Grade 3 or higher non-haematological adverse reactions included encephalopathy, unspecified pathogen infections, CRS, bacterial infection, delirium, hypertension,

hypotension, transaminases increased, and viral infection. The most common Grade 3 or higher haematological adverse reactions included lymphopenia, leukopenia, neutropenia, anaemia, and thrombocytopenia.⁸

For full details on the Special Warnings and Precautions for Use and Adverse Reactions (including appropriate management), please refer to the GB Summary of Product Characteristics (SmPC).⁸

About Kite

Kite, a Gilead Company, is a global biopharmaceutical company based in Santa Monica, California, with manufacturing operations in North America and Europe. Kite’s singular focus is cell therapy to treat and potentially cure cancer. As the global cell therapy leader, Kite has more approved CAR T indications to help more patients than any other company.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that has pursued and achieved breakthroughs in medicine for more than three decades, with the goal of creating a healthier world for all people. The company is committed to advancing innovative medicines to prevent and treat life-threatening diseases, including HIV, viral hepatitis and cancer. Gilead operates in more than 35 countries worldwide, with headquarters in Foster City, California.

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Adverse events should be reported. For the UK, reporting forms and information can be found at www.mhra.gov.uk/yellowcard or via the Yellow Card app (downloadable from the Apple app store or Google Play store). Adverse events should also be reported to Gilead at Safety_FC@gilead.com or +44 (0) 1223 897500.

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[1] Cancer Research UK. What is non-Hodgkin lymphoma? Available at: https://www.cancerresearchuk.org/about-cancer/non-hodgkin-lymphoma/about. Last accessed: January 2023.

[2] Cancer Research UK. Diffuse large B cell lymphoma. Available at: https://www.cancerresearchuk.org/about-cancer/non-hodgkin-lymphoma/types/diffuse-large-B-cell-lymphoma. Last accessed: January 2023.

[3] Dabrowska-Iwanicka A, Walewski JA. Primary mediastinal large B-cell lymphoma. Curr Hematol Malig Rep. 2014 Sep;9(3):273-83. https://doi.org/10.1007/s11899-014-0219-0.    

[4] Chaganti, S., Illidge, T., Barrington, S., et al. Guidelines for the management of diffuse large B-cell lymphoma. Br J Haematol. 2016 174: 43-56. https://doi.org/10.1111/bjh.14136.                  

[5] Crump M, Neelapu SS, Farooq U, et al. Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study. Blood. 2017 Oct 19;130(16):1800-1808. https://doi.org/10.1182/blood-2017-03-769620.

[6] Cancer Research UK. Survival. Available at: https://www.cancerresearchuk.org/about-cancer/non-hodgkin-lymphoma/survival#:~:text=Generally%20for%20people%20with%20DLBCL,or%20more%20after%20their%20diagnosis. Last accessed: January 2023.

[7] Blood Cancer UK. Facts and information about blood cancer. Available at: https://bloodcancer.org.uk/news/blood-cancer-facts/#:~:text=Overall,%20the%20five-year%20survival,who%20doesn't%20have%20cancer. Last accessed: January 2023.

[8] Yescarta. Summary of Product Characteristics. Updated December 2022. Available at: https://www.medicines.org.uk/emc/product/9439/smpc#gref. Last accessed: January 2023

^[9] Jacobson C, Locke FL, Ghobadi A, et al. Long-term (4- and 5- Year) overall survival in ZUMA-1, the pivotal study of axicabtagene ciloleucel in patients with refractory large B-cell lymphoma poster slides. Presented at: 2021 ASH; December 17, 2021; Atlanta, GA.