CAR-T Therapy Highly Effective in Treatment-Resistant CLL

07/18/17

A recent study reported an overall response rate (ORR) of 71% in patients with chronic lymphocytic leukemia (CLL) treated with anti-CD19 chimeric antigen receptor-modified T (CAR-T) cell therapy after prior treatment failure, published in the Journal of Clinical Oncology (online July 17, 2017; doi:10.1200/JCO.2017.72.8519).

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ORR for patients with CLL treated with the BTK-inhibitor ibrutinib is high. However, complete response rates are low for patients in this population after ibrutinib treatment, and researchers are continuing to examine alternative treatment options. CD19-specific CAR T-cell therapy has produced high response rate in patients with refractory B-cell acute lymphoblastic leukemia and non-Hodgkin lymphoma.

Cameron Turtle, MBBS, PhD, FRACP, FRCPA, Fred Hutchinson Cancer Research Center (Seattle, WA), and colleagues conducted a study to assess the effects of CD19 CAR T-cell therapy in patients with ibrutinib-resistant CLL. A total of 24 patients (median age, 61 years) who had received anywhere from three to nine previous therapies were included in the study. Patients received CD19 CAR T-cell therapy at one of three doses: 2 × 105, 2 × 106, or 2 × 107 CAR-T cells/kg.

Results of the trial showed that 71% of patients (n = 17) demonstrated complete or partial response following CD19 CAR T-cell therapy, as assessed by the standard measure of lymph node size by CT scans four weeks after treatment.

Adverse events were reported from the trial, most frequently cytokine release syndrome in 20 of the patients (grade 1-2, 18 patients; grade 4, one patient; grade 5, one patient). Thirty-three percent of patients (n = 8) developed neurotoxicity (grade 3, five patients; grade 5, one patient).

"It was not known whether CAR T-cells could be used to treat these high risk CLL patients," said Dr Turtle in an interview (July 17, 2017). "Our study shows that CD19 CAR T-cells are a highly promising treatment for CLL patients who have failed ibrutinib."

Furthermore, after using IGH deep sequencing in 12 of the patients, researchers found that seven patients exhibited no malignant cancer cells remaining after treatment, all of whom were alive and disease-free at a median follow-up of 6.6 months. Researchers believe that deep sequencing might be a superior measure to CT scans for predicting outcomes four weeks after CD19 CAR T-cell therapy for CLL. Further research is needed to validate this claim.—Zachary Bessette