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Chimeric antigen receptor T cells exhibit efficacy in advanced lymphoma

Tuesday, June 7, 2016

Treatment with T cells genetically modified to express chimeric antigen receptors targeting CD19 induced remission in patients with advanced B-cell lymphoma when administered with low-dose chemotherapy, according to study results presented at the ASCO Annual Meeting. John Leonard, M.D., was invited by HemOnc Today to give his perspective. Read the full article here. 

John Leonard, M.D.John Leonard, M.D. This abstract provides additional data on chimeric antigen receptor (CAR) T cells for the treatment of aggressive lymphomas. CAR T cells are very exciting, receiving much attention, and there are a lot of data coming out on their use in lymphoid malignancies. One of the challenges is to take them forward in a way that definitively demonstrates their value compared with other treatments.  This study included data from 22 patients and showed that a regimen of fludarabine and/or cyclophosphamide in a nonmyeloablative fashion, in addition to CAR T cells, could induce meaningful remissions in patients with diffuse large B-cell lymphoma (DLBCL). A few other aggressive subtypes were included, but most of the patients in this report had DLBCL. A majority of patients included in this study had a response, which is exciting, because it shows that we can observe a high response rate when patients are treated with CAR T cells. Further, the chemotherapy regimen used was attenuated in dose, so we can attribute the effect primarily to the CAR T cells and less so to the chemotherapy.

These represent additional data that show that this treatment regimen has potential in the treatment of patients with resistant, aggressive lymphoma.
As far as follow-up is concerned, we need additional studies with larger groups of patients, with longer follow-up periods, to see if these responses are going to be durable.   That is going to be quite important to see in much larger patient populations.  We also need to address the critical fact that there is an inherent selection bias in CAR T-cell therapy. There are patients who are not candidates for this type of treatment because of their age and comorbidity burden, or because they have rapidly aggressive/growing disease. Because there is an inherent delay of a few weeks required to get a patient enrolled and get them CAR T cells (and sometimes longer to even be able to be considered for a spot on a trial), some patients with aggressive lymphoma are left out because they cannot wait that long for therapy. So, there is an inherent bias toward patients who are healthy, and those which have more favorable (less rapidly growing or symptomatic) disease allowing them wait a little longer for treatment.
That being said, the lymphoma community remains excited, and it is safe to say there is a good chance this treatment will be more widely used in the future.