Ask the Doctor: Are there clinical trials showing that CAR-T is an effective treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)?

In May 2020, lymphoma-expert, Raghuveer Ranganthan, MD (Univerity of Southern California) hosted the Lymphoma Research Foundation’s Update on CAR T-Cell Therapy in Diffuse Large B-cell Lymphoma Webinar. Due to the interest surrounding CAR T-cell therapy to treat various types of lymphoma, LRF asked Dr. Rangantham to provide an answer to the following question: Are there any clinical trials showing that CAR-T cell therapy is effective in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)?

There are several small clinical trials demonstrating the effectiveness of CAR-T cell therapy to treat patients with CLL/SLL that have relapsed/refractory disease. These patient populations consist of those whose disease returns after treatment (relapsed) or whose disease does not respond to initial treatment (refractory). In fact, one of the very first CAR-T cell clinical trials involved three patients with multiple r/r CLL who received CAR-T targeting CD19, a protein on the surface of CLL tumor cells.

All three patients showed a response, with two of the three patients achieving a complete response (CR) – meaning the disappearance of signs and symptoms of the disease. A follow-up, expanded trial with 14 patients showed an overall response rate of 58 percent among the patients (8 out of 14 patients) with four patients achieving CR. At a follow-up of 40 months, none of the patients in CR had relapsed.

Overall, there have been about 10-11 clinical trials to date that have been published with CD19-targeting CAR-T cells in r/r CLL. Some patients with a partial response to CAR-T did eventually change to a CR as well, also similar to what was seen in the non-Hodgkin lymphoma trials. In general, those patients who are able to get into an eventual CR tend to stay in CR with very few relapses recorded among these patients.

Over the past few years, CLL therapy has radically changed, moving away from using chemotherapy first-line to applying more newer, targeted therapies such as venetoclax and ibrutinib. These two medications are now used in the first-line for newly diagnosed CLL/SLL, as they have demonstrated better efficacy with generally lower amounts of side effects compared to chemotherapy.

These patients who had received the newer targeted therapies also show similar rates of response as discussed above when given CAR-T after relapse. More research is needed and being done to determine how to increase the number of r/r CLL/SLL patients who respond to CAR-T therapy, additional CLL targets to pursue, and what the optimal way to boost response rates exactly is.

CAR-T cell therapies are still not FDA approved for the treatment of r/r CLL/SLL, but there is hope that status can and will change in the future. In the meantime, enrolling in a CAR-T clinical trial remains the best way for r/r CLL/SLL patients to be able to receive CAR-T therapy.

To learn more visit the chronic lymphocytic leukemia/small lymphocytic lymphoma learning center.

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