The U.S. Food and Drug Administration (FDA) has expanded the approval of the chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel to include the treatment of patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. The indication includes diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
In August 2017, tisagenlecleucel became the first FDA-approved CAR T-cell therapy when it received approval for the treatment of patients aged 25 years or younger with B-cell precursor acute lymphocytic leukemia (ALL) that is refractory or in second or later relapse. With the recent expanded approval, it is now the only CAR T-cell therapy approved for two distinct indications.
The decision was based on results from the phase II JULIET trial, which were presented at the 2017 ASH Annual Meeting by Stephen J. Schuster, MD. Among the 68 JULIET participants evaluable for efficacy, half responded to treatment, with 32 percent of patients achieving a complete response and 18 percent achieving a partial response. The median duration of response was not reached.
Cytokine release syndrome, a potentially fatal adverse event (AE) associated with CAR T-cell therapy, occurred in 23 percent of 106 patients treated with tisagenlecleucel. Eighteen percent of all infused patients experienced grade 3/4 neurologic events, including 11 percent who experienced encephalopathy. Neurotoxic AEs were managed with supportive care and there were no deaths attributed to neurologic events, the investigators reported.
Novartis, the manufacturer of tisagenlecleucel, also announced a new “indication-based” pricing model for the therapy: When used to treat lymphoma, tisagenlecleucel costs $373,000, compared with $475,000 for the same therapy when used to treat ALL. This controversial type of pricing sets costs based on the relative population frequency of approved indications, rather than distinct development or manufacturing costs or market forces.
Source: Novartis press release, May 1, 2018; FDA press release, May 1, 2018.