Researchers combined anti-CD19 CAR T-cell immunotherapy with ibrutinib to test the hypothesis that the combination will yield a higher rate of complete response (CR) than either agent administered alone.
Patients participating in this pilot trial were not in CR despite receiving ibrutinib for at least 6 months. Of the 19 patients receiving immunotherapy infusions, 15 were male, the median age was 62 years (range, 42-76), and 5 were receiving first-line ibrutinib. Of the remaining 14, the median number of prior therapies was 2, and 3 patients had received prior CART19 therapy without ibrutinib. Eleven patients had chromosome 17p or TP53 abnormalities, and 3 had chromosome 11q22 or ATM abnormalities. All 19 patients received at least 2 CTL119 doses, and 14 patients received all 3 scheduled doses. In total, 18 of 19 (95%) patients experienced cytokine release syndrome (CRS); CRS was grades 1/2 and 3/4 in 15 and 3 patients, respectively.
As of July 2018, 18 of 19 patients remained alive (95%) with median follow-up of 18.5 months for the surviving patients. One patient died due to cardiac arrhythmia in the setting of grade 4 neurotoxicity. In patients not achieving CR despite at least 6 months of ibrutinib who were treated with humanized CART19, researchers found an International Workshop on Chronic Lymphocytic Leukemia CR rate of 43%. At 3 months, patients had a bone marrow remission rate of 94%, including a 78% minimal residual disease (MRD)-negative response by deep sequencing. CRS was frequent but generally mild to moderate and did not require anticytokine therapy in most patients. In total, 16 of 18 patients remain in morphologic and/or flow CR at last follow-up.
Although the study size was small, these high rates of MRD-negativity suggest that the combination of CTL119 with ibrutinib may hold promise for patients with chronic lymphocytic leukemia. Researchers intend to continue testing the combination of anti-CD19 CAR T-cell immunotherapy and ibrutinib in larger studies.
Gill SI, et al. ASH 2018. Abstract 298.