Point-of-care anti-CD19 CAR T-cells for treatment of relapsed and refractory aggressive B-cell lymphoma

Meirav Kedmi*, Roni Shouval, Shalev Fried, David Bomze, Joshua Fein, Zachary Cohen, Ivetta Danilesko, Noga Shem-Tov, Ronit Yerushalmi, Elad Jacoby, Michal Besser, Avichai Shimoni, Arnon Nagler, Abraham Avigdor

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Anti CD19 chimeric antigen receptor (CAR) T-cell therapy has transformed the care of relapsed and refractory aggressive B-cell lymphoma. However, financial toxicity and manufacturing time represent barriers to its widespread implementation. Study applicability, toxicity, and efficacy of a locally produced autologous CD19-directed CAR T-cell product were studied. We performed a phase 1b/2 clinical trial with a point-of-care (POC) CAR T-cell product that contains a CD28 costimulatory domain. Adult patients with aggressive B-cell lymphoma or transformed low-grade lymphoma who received at least 2 prior regimens were eligible. A total of 73 patients, with a median age of 49 years, met inclusion criteria. CAR T-cell production time from apheresis was 10 days (interquartile range 10-11), negating the need for bridging chemotherapy. Overall and complete response rates were 62.5% and 37.5%. Median progression-free and overall survival were 3.7 and 12.1 months, respectively. Overall and progression-free survival at 12 months were 52.1% (confidence interval [CI]: 40.8%-66.5%) and 40% (CI: 30%-53.7%), respectively. Patients who achieved response had longer progression-free and overall survival. Grade 3-4 cytokine release syndrome was observed in 9.5% of the patients, and immune effector cell-associated neurotoxicity syndrome grade 3-4 in 21.9%. No deaths occurred due to CAR T-cell toxicity. Fifteen patients (20%) underwent allogeneic stem cell transplantation at a median time of 60 days after CAR T-cell therapy; 8 were alive at last follow-up. Of the 6 patients who underwent the transplantation in complete response 2 deceased because of toxicity. POC CAR T-cells are a feasible therapeutic option in aggressive B-cell lymphoma. They provide good efficacy while minimizing production time and the need for bridging therapy.

Original languageEnglish
Pages (from-to)251-257
Number of pages7
JournalTransplantation and Cellular Therapy
Volume28
Issue number5
DOIs
StatePublished - May 2022

Funding

FundersFunder number
National Institutes of Health
National Cancer InstituteP30CA008748

    Keywords

    • Aggressive B-cell lymphoma
    • Allogeneic stem cell transplantation
    • CAR T-cell
    • Point of care

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