NICE Issues Recommendations for Axicabtagene Ciloleucel for Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma and Primary Mediastinal Large B-Cell Lymphoma

More evidence on axicabtagene ciloleucel is being collected

On 23 January 2019, NICE released Technology appraisal guidance [TA559] with evidence-based recommendationon axicabtagene ciloleucel therapy (Yescarta, Kite Pharma) for treatment of diffuse large B-cell lymphoma and primary mediastinal B-cell lymphoma in adults after 2 or more systemic therapies. It is recommended for use within the Cancer Drugs Fund as an option for treating relapsed or refractory disease, 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 axicabtagene ciloleucel 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.

There is no standard treatment for relapsed or refractory diffuse large B‑cell lymphoma or primary mediastinal large B‑cell lymphoma after 2 or more systemic therapies. Best supportive care is used and usually includes salvage chemotherapy.

Axicabtagene ciloleucel is an immunocellular chimeric antigen receptor (CAR) T‑cell therapy. It contains the patient's own T cells that have been modified genetically in the laboratory so that they make CAR. CAR can attach to another protein on the surface of cancer cells, CD19. When axicabtagene ciloleucel is given to the patient, the modified T cells attach to and kill cancer cells.

Treatment with axicabtagene ciloleucel comprises a single‑dose intravenous infusion of axicabtagene ciloleucel (anti‑CD19 CAR T cells in about 68 ml). It is intended for autologous use only and at the following dosage:

2×106 anti‑CD19 CAR T cells per kg body weight (range: 1×106 to 2.4×106 cells per kg), with at most 2×108 anti‑CD19 CAR T cells.

Evidence from a small, single-arm study suggests that patients having axicabtagene ciloleucel have clinically meaningful overall and progression-free survival and good response rates. However, the evidence is uncertain because there is limited follow‑up and no direct data comparing axicabtagene ciloleucel with salvage chemotherapy. Limitations in the available data mean that the exact size of the benefit of axicabtagene ciloleucel compared with salvage chemotherapy is unknown. There is also not enough evidence to determine the costs of treating side effects.

Axicabtagene ciloleucel meets NICE's criteria to be considered a life-extending treatment at the end of life. The most plausible cost-effectiveness estimates for axicabtagene ciloleucel compared with salvage chemotherapy are uncertain because survival data on axicabtagene ciloleucel are immature. However, the range of cost-effectiveness estimates shows that axicabtagene ciloleucel has plausible potential to be cost effective, and collecting further data on progression-free survival, overall survival and immunoglobulin usage will reduce the uncertainty in the evidence. Therefore, axicabtagene ciloleucel is recommended for use as an option within the Cancer Drugs Fund.

The price was submitted as commercial in confidence. The company has a commercial agreement. This makes axicabtagene ciloleucel available to the NHS with a discount. The details of the arrangement are commercial in confidence. It is the company's responsibility to let relevant NHS organisations know the details of the commercial arrangement.

More evidence on axicabtagene ciloleucel is being collected, until around February 2022. 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.