The FDA granted breakthrough therapy designation for JCAR017 – a CD19-targeted chimeric antigen receptor (CAR) T-cell therapy – for patients with relapsed/refractory, aggressive large B-cell non-Hodgkin lymphoma (NHL), specifically those with diffuse large B-cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma, grade 3B follicular lymphoma (FL), or disease not otherwise specified (de novo or transformed from indolent lymphoma).
The decision was based on data from the multicenter, phase I TRANSCEND study, which demonstrated that JCAR017 (at an infusion dose of 50 million cells) led to a 60 percent complete response rate and 80 percent overall response rate in patients with NHLs.
The study included patients (median age = 61 years; age range = 37-79 years) with DLBCL (n=15), transformed DLBCL (n=10), mantle cell lymphoma (MCL; n=2), or grade 3b FL (n=1). The median number of prior therapies was four (range = 1-8 therapies), and 57 percent of patients had received hematopoietic cell transplantation (allogeneic = 14%; autologous = 46%).
Prior to JCAR017 infusion, patients received lympho-depleting chemotherapy with fludarabine 30 mg/m2 and cyclophosphamide 300 mg/m2 daily for three days.
After three months of follow-up, 42 percent of assessable patients remained in response.
The most common treatment-related adverse events included fatigue (39%), cytokine release syndrome (CRS; 36%), decreased appetite (29%), constipation (25%), vomiting (25%), diarrhea (21%), dizziness (21%), headache (18%), hypertension (18%), nausea (18%), and peripheral edema (18%). There was one grade 5 respiratory failure, which the researchers deemed potentially related to JCAR017, in a patient with MCL who progressed on JCAR017 and began subsequent therapy.
No patients experienced severe CRS, although 36 percent of patients had grade 1/2 CRS, and one patient required treatment with tocilizumab. In addition, five patients (14%) had severe neurotoxicity. All were resolved with treatment.
The European Medicines Agency’s Committee for Medicinal Products for Human Use and Committee for Advanced Therapies also granted JCAR017 access to the priority medicines scheme (known as PRIME) for relapsed/refractory DLBCL.
Last year, JCAR015 – another CAR therapy produced by Juno Therapeutics – was placed on a clinical hold by the FDA due to two patient deaths related to cerebral edema. The company said the hold on JCAR015 did not impact trials and plans for its other CD19-directed CAR T-cell product, JCAR017.
Source: Juno Therapeutics press release, December 21, 2016.