On May 1, 2018, the FDA granted approval to Novartis Pharmaceuticals Corp. to market KYMRIAH® (tisagenlecleucel) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma, who have already received two or more prior lines of systemic therapy . Tisagenlecleucel is a CD-19-targeted autologous chimeric antigen receptor (CAR) T-cell therapy designed for the treatment of patients with B-cell malignancies (CD-19 expressing cells). It has already been approved in 2017 for the treatment of patients, up to 25 years of age with B-cell precursor acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse, after a phase 1-2a study concluded with impressive efficacy results .
The approval for R/R LBCL was based on the results of a single-arm, open-label, multi-center, phase 2 trial, JULIET, examining the safety and efficacy of tisagenlecleucel therapy for the treatment of adults with R/R LBCL (NCT02445248) . Out of 68 evaluable patients, the overall response rate was 50% and the complete response rate was 32% . The median duration of response experienced was longer in the patients who achieved a complete response than those who achieved only a partial response, not reached vs. 3.4 months, respectively. Despite the impressive efficacy results, safety concerns were raised as cytokine release syndrome was experienced by 74% of patients on study, three of whom died . Tisagenlecleucel was the first CAR T-cell therapy approved by the FDA and has provided proof-of-concept for future CAR T-cell therapy development.
- KYMRIAH™ (tisagenlecleucel) suspension for intravenous infusion. Vaccines, Blood & Biologics May 1, 2018 [cited 2018 May 9]; Available from: https://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/ApprovedProducts/UCM573941.pdf.
- Study of Efficacy and Safety of CTL019 in Adult DLBCL Patients (JULIET). ClinicalTrials.gov April 17, 2018 [cited 2018 May 9]; Available from: https://clinicaltrials.gov/ct2/show/NCT02445248.