In a nutshell
This paper studied the effect of lymphodepletion chemotherapy and CAR-T cell infusion in patients with chronic lymphocytic leukemia who did not respond to ibrutinib (Imbruvica) therapy. This was found to be a highly effective treatment.
Some background
Chronic lymphocytic leukemia (CLL) is a cancer of the blood forming cells. Ibrutinib is a drug used in the treatment of CLL that has come back or not responded to treatment. However, some patients with high risk disease do not respond to ibrutinib. Lymphodepletion chemotherapy followed by CD19 chimeric antigen receptor-modified T (CAR-T) cell infusion is one type of treatment. CAR-T cells are cells made from genetically modifying a patient’s own immune cells so that they can be transferred back into the patient to kill cancer cells. Lymphodepletion chemotherapy is chemotherapy that allows CAR-T cells to grow better. It is suggested that this treatment would be effective in patients with CLL that has not responded to treatment.
Methods & findings
24 patients with CLL who previously did not respond to ibrutinib were studied. They received lymphodepletion chemotherapy with cyclophosphamide and/or fludarabine. 20 out of 24 patients received both cyclophosphamide and fludarabine.
71% of patients showed a response to treatment 4 weeks after CAR-T cell infusion. Among 19 patients who received cyclophosphamide and fludarabine chemotherapy, 74% responded to treatment. 21% of these 19 patients had a complete response to treatment (no evidence of disease).
Of 22 patients who had bone marrow disease before treatment, 21 patients had a bone marrow evaluation 4 weeks after CAR-T cells. 88% of patients who received cyclophosphamide and fludarabine chemotherapy had no disease in the bone marrow.
83% of patients developed cytokine release syndrome. This syndrome is caused by the increase in CAR-T cells, leading to symptoms like fever, nausea, chills, headache and rash. Of these patients, 25% required treatment with steroids. 33% of patients had neurotoxicity (damage to nervous system). All cases of neurotoxicity were reversible, except for one patient who died from complications.
The bottom line
The authors concluded that treatment with CAR-T cells is highly effective in patients with CLL who have failed with ibrutinib.
The fine print
There was a small number of patients studied.
Published By :
Journal of clinical oncology
Date :
Jul 17, 2017
