NICE Recommends Tisagenlecleucel for Pediatric R/R B-ALL

The United Kingdom’s National Institute for Health and Care Excellence (NICE) has recommended tisagenlecleucel (Kymriah) for the treatment of pediatric and young adult patients up to and including 25 years of age with B-cell acute lymphoblastic leukemia (B-ALL) who have not responded to treatment, relapsed after stem-cell transplant, or experienced relapse 2 or more times. The agent has been available in the United Kingdom since December 2018 via the National Health Service’s (NHS) Cancer Drugs Fund; the new guidance recommends its routine rollout.¹

This recommendation is supported by pooled findings from 3 clinical trials: the phase 2 ELIANA (NCT02435849) and ENSIGN (NCT02228096) studies, as well as the phase 1/2a B2101J trial (NCT01626495). The median overall survival (OS) was 48 months in the pooled dataset (n = 200). Comparatively, the median OS for the standard-of-care treatments blinatumomab (Blincyto) and salvage chemotherapy were 7.5 months and 3 months, respectively.^1,2

“I am delighted that we have been able to recommend continued use of this innovative treatment, which is already making a huge difference to the lives of children and young adults,” Helen Knight, director of medicines evaluation at NICE, said in a press release. “The evidence from its use in the Cancer Drugs Fund [CDF] and clinical trials shows it can offer an effective treatment, helping people live longer and with a better quality of life and could represent a potential cure for some people. Today’s news illustrates how NICE is determined to get the best care to patients fast, while ensuring value for money for the taxpayer.”¹

“Novartis have been working with NHS England to maintain access to CAR-T therapy in the areas of highest unmet need since its first approval in 2018,” Marie-Andrée Gamache, president and managing director of Novartis UK and Ireland, added in a press release. “Cell and gene therapies are another example of how we’re reimagining medicine to make a real difference to patients’ lives. While in the Cancer Drugs Fund, tisagenlecleucel has been used to treat 133 children and young adults with a potentially deadly form of cancer and today’s NICE recommendation provides the opportunity for it to continue being a treatment option for many more.”³

Tisagenlecleucel is a CAR T-cell therapy that is manufactured from autologous T cells obtained via leukapheresis. These cells are genetically engineered with a CAR protein that enables the T-cells to identify and kill CD-19–expressing normal and malignant cells. The agent was the first CAR T-cell therapy approved by the FDA and gained approval in August 2017 for the treatment of patients up to 25 years of age with B-ALL that is refractory or in second or later relapse. The approval was supported by findings from the ELIANA trial.⁴

ELIANA was a single-arm, open-label, multicenter study of tisagenlecleucel in patients up to 25 years of age with relapsed or refractory B-ALL. Key inclusion criteria included adequate organ function, a life expectancy of more than 12 weeks, bone marrow with at least 5% lymphoblasts at screening, Karnofsky (age ≥16 years) or Lansky (age < 16 years) performance status (PS) of at least 50 at screening, and documented CD19 tumor expression within 3 months of study entry for patients with relapsed disease. The primary end point was overall remission rate (ORR); secondary end points included OS, best overall response, duration of response (DOR), relapse-free survival (RFS), event-free survival (EFS), and pharmacokinetics.⁵

ENSIGN was a multicenter, single-arm study of tisagenlecleucel conducted in the United States that enrolled patients 3 to 21 years of age with relapsed or refractory B-ALL and lymphoblastic lymphoma. Eligible patients needed to have adequate organ function, a life expectancy over 12 weeks, and a Karnofsky (age ≥ 16 years) or Lansky (age < 16 years) PS of at least 50 at screening. The primary end point was ORR; secondary end points included OS, RFS, EFS, DOR, and pharmacokinetics.⁶

Additional results from the pooled analysis from the NICE draft guidance demonstrated that long-term EFS and OS were comparable between the 3 data sources. Additionally, data regarding the use of tisagenlecleucel in the NHS indicated that the 24-month OS rate was 72%.^1,2

In terms of safety, 81% of patients in the pooled dataset experienced any-grade cytokine release syndrome and 51% experienced any-grade hypogammaglobulinemia. Additionally, NICE noted that the price of tisagenlecleucel is £282,000 per infusion and the agent is available to the NHS with a discount due to a commercial arrangement.^1,2

“It’s great news that this potentially curative drug is now being rolled out for routine use in the NHS for treating children and young people with an aggressive type of leukemia,” Peter Clark, MA, MD, FRCP, a professor and Clinical Lead for NHS England, said in the press release. “Tisagenlecleucel is just the latest drug to be recommended for routine use on the NHS and follows its use in certain circumstances for patients as part of our CDF since 2018, where it has shown its effectiveness in helping more children and young people live longer, healthier lives.”¹

References

1. Children and young adults to benefit after NICE recommends personalised immunotherapy to treat blood cancer be made routinely available on the NHS. News release. National Institute for Health Care Excellence. April 11, 2024. Accessed April 11, 2024. https://www.nice.org.uk/News/Article/children-and-young-adults-to-benefit-after-nice-recommends-personalised-immunotherapy-to-treat-blood-cancer-be-made-routinely-available-on-the-nhs
2. Final draft guidance. Tisagenlecleucel for treating relapsed or refractory B-cell acute lymphoblastic leukaemia in people 25 years and under (MA review of TA554). National Institute for Health Care Excellence. April 11, 2024. Accessed April 11, 2024. https://www.nice.org.uk/guidance/indevelopment/gid-ta11381/documents
3. Children and young adults with acute type of leukaemia to get continued access to CAR-T treatment following NICE recommendation. News release. Novartis. April 11, 2024. Accessed April 11, 2024. https://www.novartis.com/uk-en/news/media-releases/children-and-young-adults-acute-type-leukaemia-get-continued-access-car-t-treatment-following-nice-recommendation
4. FDA approves tisagenlecleucel for B-cell ALL and tocilizumab for cytokine release syndrome. FDA. August 30, 2017. Accessed April 11, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tisagenlecleucel-b-cell-all-and-tocilizumab-cytokine-release-syndrome
5. Study of efficacy and safety of CTL019 in pediatric ALL patients (ELIANA). ClinicalTrials.gov. Updated February 13, 2024. Accessed April 11, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT02435849
6. Study of efficacy and safety of CTL019 in pediatric ALL patients (ENSIGN). ClinicalTrials.gov. November 23, 2020. Accessed April 11, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT02228096