床旁抗 CD19 CAR-T 细胞治疗复发/难治性侵袭性 B 细胞淋巴瘤

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.