High rate of durable complete remission in follicular lymphoma after CD19 CAR-T cell immunotherapy

Abstract

Patients with follicular lymphoma (FL) with early relapse after initial chemoimmunotherapy, refractory disease, or histologic transformation (tFL) have limited progression-free and overall survival. We report efficacy and long-term follow-up of 21 patients with relapsed/refractory (R/R) FL (n = 8) and tFL (n = 13) treated on a phase 1/2 clinical trial with cyclophosphamide and fludarabine lymphodepletion followed by infusion of 2 × 106 CD19-directed chimeric antigen receptor-modified T (CAR-T) cells per kilogram. The complete remission (CR) rates by the Lugano criteria were 88% and 46% for patients with FL and tFL, respectively. All patients with FL who achieved CR remained in remission at a median follow-up of 24 months. The median duration of response for patients with tFL was 10.2 months at a median follow-up of 38 months. Cytokine release syndrome occurred in 50% and 39%, and neurotoxicity in 50% and 23% of patients with FL and tFL, respectively, with no severe adverse events (grade ≥3). No significant differences in CAR-T cell in vivo expansion/persistence were observed between FL and tFL patients. CD19 CAR-T cell immunotherapy is highly effective in adults with clinically aggressive R/R FL with or without transformation, with durable remission in a high proportion of FL patients. This trial was registered at clinicaltrials.gov as #NCT01865617.

Conflict of interest statement

Conflict-of-interest disclosure: K.A.H. has served on advisory boards for Celgene; S.R.R. holds equity, has served as an advisor, and has patents licensed to Juno Therapeutics, a Celgene/Bristol-Myers Squibb company; is a founder of Lyell Immunopharma; and has served on advisory boards for Adaptive Biotechnologies and Nohla; D.G.M. has received research funding from Kite Pharma, a Gilead Company, Juno Therapeutics, a Celgene/Bristol-Myers Squibb company, and Celgene; has served on advisory boards for Kite Pharma, Gilead, Genentech, Novartis, and Eureka Therapeutics; C.J.T. receives research funding from Juno Therapeutics, a Celgene/Bristol-Myers Squibb company, and Nektar Therapeutics; has patents licensed to Juno Therapeutics, a Celgene/Bristol-Myers Squibb company; has served on advisory boards and has equity ownership in Caribou Biosciences, Eureka Therapeutics, and Precision Biosciences; and has served on advisory boards for Aptevo, Juno Therapeutics, a Celgene/Bristol-Myers Squibb company, Kite Pharma, a Gilead Company, Humanigen, Nektar Therapeutics, Allogene, and Novartis. The remaining authors declare no competing financial interests.

© 2019 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

PFS and OS in patients with FL after CD19 CAR-T cell immunotherapy. KM estimates of PFS (A-B) and OS (C-D) in patients with FL (A-C) and transformed FL (B-D) who achieved CR (blue) and in all patients (red). The numbers of patients at risk at 6-month intervals are indicated.