Chimeric Antigen Receptor-Modified T Cell Immunotherapy for Relapsed and Refractory Adult Burkitt Lymphoma

Abstract

Patients with Burkitt lymphoma who are refractory to initial therapy or who relapse after undergoing intensive chemotherapy and autologous stem cell transplantation (ASCT) usually have a poor prognosis. While there has been considerable progress in the use of chimeric antigen receptor-modified (CAR) T cell immunotherapy for the treatment of relapsed and refractory (r/r) malignancies, explicit data on adult patients with r/r Burkitt lymphoma are limited. We conducted two single-arm clinical trials to evaluate the clinical efficacy and toxicity of CD19/CD22 CAR T cell immunotherapy both alone (trial A) and in combination with ASCT (trial B) in adult patients with r/r Burkitt lymphoma. In total, 28 adult patients with r/r Burkitt lymphoma were enrolled [trial A (n = 15) and trial B (n = 13)]. The median doses of CD22 and CD19 CAR T cell infusions were 4.1 × 10⁶/kg and 4.0 × 10⁶/kg, respectively. Subsequently, after CAR T cell infusion, overall and complete responses were observed in 19 (67.9%) and 16 (57.1%) patients, respectively. The cumulative incidence rates of grade 2-4 cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome were 39.3% (11/28) and 10.7% (3/28), respectively. After a median follow-up duration of 12.5 months, 16 patients (5 in trial A and 11 in trial B) survived. Both the estimated 1-year progression-free and overall survival rates were 55.6%. Our preliminary results indicated that salvage therapy with CD19/CD22 CAR T cell infusion alone and that in combination with ASCT are effective in treating some adult patients with r/r Burkitt lymphoma.

Keywords: Burkitt lymphoma; chimeric antigen receptor; cytokine release syndrome; immune effector cell-associated neurotoxicity syndrome; immunotherapy; transplantation.