NICE Issues Technology Appraisal Guidance on Tisagenlecleucel for Treating Relapsed or Refractory DLBCL

On 13 March 2019, NICE issued evidence-based recommendations on tisagenlecleucel therapy (Kymriah, Novartis) for treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL) in adults after 2 or more systemic therapies.

More evidence on tisagenlecleucel is being collected, until 2023. After this NICE will decide whether or not to recommend it for use on the NHS and update the guidance. It will be available through the Cancer Drugs Fund until then.

Tisagenlecleucel is an immunocellular CAR T‑cell therapy. It contains the patient's own T cells that have been modified genetically in the laboratory so that they make a protein called chimeric antigen receptor (CAR). CAR can attach to another protein on the surface of cancer cells called CD-19. When tisagenlecleucel is given to the patient, the modified T cells attach to and kill cancer cells, thereby helping to clear the cancer from the body.

Treatment with tisagenlecleucel comprises a single‑dose intravenous infusion of tisagenlecleucel. It is intended for autologous use only and the dosage for adults with DLBCL is 0.6 to 6.0x108 CAR-positive viable T cells.

Tisagenlecleucel therapy is recommended for use within the Cancer Drugs Fund as an option for treating relapsed or refractory DLBCL in adults after 2 or more systemic therapies, only if the conditions in the managed access agreement are followed.

This recommendation is not intended to affect both treatment in preparation for and treatment with tisagenlecleucel that was started in the NHS before this guidance was published. Patients having treatment outside this recommendation may continue without change to the funding arrangements in place for them before this guidance was published, until they and their NHS clinician consider it appropriate to stop.

Why the appraisal committee made these recommendations

There is no standard treatment for relapsed or refractory DLBCL after 2 or more systemic therapies. Salvage chemotherapy is the most common treatment option.

Evidence from a single-arm study with short follow-up and a small observational study suggests that patients having tisagenlecleucel may live for longer, or have more time before their disease relapses. But longer follow-up from the study is needed and there are no data directly comparing tisagenlecleucel with salvage chemotherapy. To assess the comparative effectiveness of tisagenlecleucel and salvage chemotherapy, data from the first CORAL extension study are used. Limitations in the available data mean that the exact size of the benefit of tisagenlecleucel compared with salvage chemotherapy is difficult to establish.

Tisagenlecleucel meets NICE's criteria to be considered a life-extending treatment at the end of life. All the cost-effectiveness estimates for tisagenlecleucel compared with salvage chemotherapy are uncertain because of limitations in the data. Because some of these estimates are higher than what NICE normally considers an acceptable use of NHS resources and are associated with a high degree of uncertainty, tisagenlecleucel cannot be recommended for routine use in the NHS.

Collecting more data on progression-free survival, overall survival and immunoglobulin usage will reduce the uncertainty in the evidence. Therefore, tisagenlecleucel is recommended for use in the Cancer Drugs Fund.

The list price for tisagenlecleucel is 282,000 GBP per infusion (company submission).

The company has a commercial arrangement (managed access agreement with a simple discount and rebate scheme). This makes tisagenlecleucel available to the NHS with a discount. The size of the discount is commercial in confidence. It is the company's responsibility to let relevant NHS organisations know details of the discount.