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Clinical Trial
. 2019 Aug 15;134(7):636-640.
doi: 10.1182/blood.2019000905.

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

Alexandre V Hirayama  1 , Jordan Gauthier  1 , Kevin A Hay  1   2 , Jenna M Voutsinas  1 , Qian Wu  1 , Barbara S Pender  1 , Reed M Hawkins  1 , Aesha Vakil  1 , Rachel N Steinmetz  1 , Stanley R Riddell  1   3 , David G Maloney  1   3 , Cameron J Turtle  1   3
Affiliations
Clinical Trial

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

Alexandre V Hirayama et al. Blood. .

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.

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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.

Figures

None
Graphical abstract
Figure 1.
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.
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Comment in

References

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