Kymriah (tisagenlecleucel), developed by Novartis, has not been recommended as a treatment for adults with aggressive diffuse large B-cell lymphoma (DLBCL) for England’s National Health Service (NHS).
The National Institute for Health and Care Excellence (NICE), the U.K.’s national agency providing guidance on healthcare, did not recommend Kymriah for adults with DLBCL — the most common form of non-Hodgkin’s lymphoma — whose cancer has come back (relapsed) or did not respond (refractory) to two or more lines of systemic therapy.
This information was made public in a draft guidance published by the agency.
The negative appraisal of Kymriah, a chimeric antigen receptor (CAR) T-cell therapy, was based on its cost and the lack of studies supporting its long-term effectiveness, or comparing its benefit to the current treatment, salvage chemotherapy.
However, NICE says that Kymriah has significant clinical benefits, and encourages future discussions on its cost-effectiveness.
“We face an uncertain time regarding access to CAR T cell therapies for patients with diffuse large B cell lymphoma,” Karl Peggs, a professor and immunotherapy expert at University College London, said in a news release. “The early results are exciting but remain relatively limited, making it difficult to assess the true benefits of these therapies over existing treatments.”
The recommendation, however, is not intended to advise people to stop taking Kymriah who have already started taking it. “People having treatment outside this recommendation may continue without change to the funding arrangements in place for them,” NICE stated in its draft guidance.
The appraisal is not definitive yet. The final decision about whether to support the use of the therapy in England’s NHS will be made at a final committee meeting on Oct. 23.
Until then, Novartis can submit additional data and there will be further negotiations between the company and NICE about the cost of the treatment.
Kymriah is a CAR T-cell therapy approved by the U.S. Food and Drug Administration and by the European Medicines Agency (EMA) for children and adolescents with relapsed or treatment-resistant B-cell acute lymphoblastic leukemia (ALL) and adults with relapsed or refractory DLBCL.
Two weeks ago, England’s NHS announced that treatment with Kymriah will be state-funded for children and young adults with ALL.
Treatment with Kymriah involves taking a patient’s own immune system T-cells and genetically engineering them in the lab to express a chimeric antigen receptor (CAR) which recognizes a protein called CD19, priming them to identify and eliminate normal and malignant B-cells. The engineered T-cells, which are more prone to recognize and kill cancer cells, are infused back into the patient.
The FDA’s decision to approve Kymriah for DLBCL was based on the JULIET Phase 2 clinical trial (NCT02445248), which recruited 106 patients in 10 countries across Europe, the U.S., Canada, Australia, and Japan. Kymriah eradicated cancer in 32% of patients evaluated at the time of data analysis (68 patients).
Half of these patients also achieved some degree of tumor shrinkage and more than half were still responding to the therapy at the time of data analysis, which indicates a sustained response.
But the treatment could also cause major side effects, including severe neurological problems and serious infections.
Severe or life-threatening cytokine release syndrome — which is caused by high-level immune activation — occurred in 23% of patients; severe neurologic events were seen in 18%; and infections were observed in 25% of patients. No deaths were attributed to neurological events.
Emlyn Samuel, Cancer Research UK‘s head of policy development said that although CAR T-cell therapies have shown great promise in some lymphoma patients, the process of manufacturing the drug is complex and very expensive.
“We urge NICE, NHS England and the manufacturer to work together so that the best possible evidence on the drug’s effectiveness is available when this decision is reviewed next month, and to agree to a deal to ensure affordable access for patients as soon as possible,” he said.