Ultralow-Dose Interleukin 10-Expressing Chimeric Antigen Receptor T Cells in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Nonrandomized Clinical Trial.
Ultralow-dose IL-10 chimeric antigen receptor T cells achieved responses in most relapsed diffuse large B-cell lymphoma patients
Ultralow-Dose Interleukin 10-Expressing Chimeric Antigen Receptor T Cells in Relapsed/Refractory Diffuse Large B-Cell Lymphoma: A Nonrandomized Clinical Trial.
IMPORTANCE: Interleukin (interleukin)-10 expressing CD19 chimeric antigen receptor (chimeric antigen receptor) T cells (META 10-19) have demonstrated encouraging clinical activity in B-cell acute lymphoblastic leukemia, but their safety and efficacy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (diffuse large B-cell lymphoma) remain unknown.
To evaluate the safety and efficacy of META 10-19 in patients with R/R diffuse large B-cell lymphoma.
DESIGN, SETTING, AND PARTICIPANTS: This nonrandomized, phase 1 clinical trial was conducted at the First Affiliated Hospital of Zhejiang University School of Medicine.
One patient died before response assessment because of disease-related gastrointestinal complications.
Cytokine release syndrome occurred for 12 patients (grade 1: n = 8; grade 2: n = 3; grade 3: n = 1), and immune effector cell-associated neurotoxicity syndrome occurred for 2 patients (grade 1: n = 1; grade 2: n = 1).
Robust in vivo chimeric antigen receptor T-cell expansion was observed across dose levels, with a median (range) peak expansion of 660.7 (30.7-10 562.3) cells/µL.
At data cutoff, 5 patients experienced a maintained complete remission and 7 experienced disease relapses or progression (2 with CD19 negative relapses).
The results of this nonrandomized clinical trial suggest that ultralow-dose META 10-19 demonstrated promising antitumor activity and a manageable safety profile in patients with R/R diffuse large B-cell lymphoma.
Further investigation in larger cohorts is warranted.