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

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.

Keywords: Aggressive B-cell lymphoma; Allogeneic stem cell transplantation; CAR T-cell; Point of care.

Figure 1:. Response and Survival outcomes of the study population.

A. Alluvial plot describing disease status at apheresis and at day 28. Most of the patients achieved PR or CR. B. Overall survival of the study population - one-year OS of 52.1%. C. Progression-free survival of the study population - one year PFS of 40%. D. Landmark analysis of the patients that reached their first imaging evaluation pot CAR T-cell infusion. OS is significantly better in the patients that achieved CR or PR vs. SD/PD. E. Duration of response significantly better in the patients that achieved CR vs. PR.

Figure 2:. Swimmer plot of the 15 patients that underwent allo-SCT post CAR-T cell therapy.

Six patients achieved CR and 9 PR post CAR T-cell. Seven patients died post-transplant, of them 3 patients that achieved CR post CAR-T.