Study: CAR T-Cell Therapy Highly Effective in High-Risk Chronic Lymphocytic Leukemia

Kelly Davio

CD19 CAR T cells are highly effective in high-risk patients with chronic lymphocytic leukemia (CLL) who have failed to respond to treatment with ibrutinib, a Bruton’s tyrosine kinase inhibitor, according to a study by Cameron J. Turtle, MD, and colleagues, newly published in the Journal of Clinical Oncology.

CLL is the most common leukemia in adults, and patients with CLL who have high-risk disease often have shorter survival. For patients who cannot tolerate aggressive chemotherapy, ibrutinib is often used, but complete response (CR) rate with this therapy is low, and some patients are intolerant to the treatment. CD19 CAR T-cell therapy shows promise for these patients; the recent, open-label phase 1 and 2 trial showed that CD19 CAR T cells induced durable remissions in some patients with CLL.

In the study, 24 patients with high-risk, relapsed or refractory CLL received lymphodepleting chemotherapy followed by an infusion of CD19 CAR T cells at 1 of 3 dose levels (2 x 105, 2 x 106, or 2 x 107 CAR T cells/kg). All of the patients had previously received ibrutinib; 19 had experienced progression while taking ibrutinib, and 3 were intolerant to the therapy. All of the patients discontinued ibrutinib before undergoing lymphodepletion, as the safety of concurrent CAR T-cell and ibrutinib therapy has not been established.  

The researchers found the following:  
Six patients who had relapsed disease after 1 cycle of lymphodepletion and CAR T cells received a second cycle at either the same dose they had previously received (n = 1) or a 10-fold higher dose (n = 5). Among these patients, 2 achieved CR, and no residual CLL was detected.
 
The researchers noted that, while bone marrow disease was highly responsive to CAR T cells, bulky nodal disease was less responsive—a finding that suggests that the malignant lymph node environment may impair the CAR T-cell infiltration or function. The authors suggest that CAR T-cell therapy could be used while ibrutinib-induced mobilization of lymph node disease into blood or marrow is still effective in order to improve CR.
 
The authors concluded that CD19 CAR T-cell therapy is highly effective, with manageable toxicity, in high-risk CLL, including ibrutinib-refractory CLL, and that using this therapy can create sustained molecular remissions and improve prognosis.
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