Looking Ahead: What's New In CAR T-Cell Therapy for Hematologic Malignancies

Jim Kochenderfer, M.D., lends insight to the future of CAR T-cell therapy for hematologic malignancies.
BY REBECCA BERNASKI
PUBLISHED: MARCH 24, 2017
For patients with hematologic malignancies, promise lies in the immunotherapy technique of adoptive cell transfer (ACT). The building blocks of this therapy are T cells which are collected and then altered to produce chimeric antigen receptors or CARs. These CAR T cells are then infused into the patient to multiply, recognize cancer cells and kill those cancer cells that harbor the antigen.

In an interview with CURE, Jim Kochenderfer, M.D. and investigator from the National Cancer Institute in Bethesda, discussed anti-CD19 CAR-T cell gene therapy, results from recent trials and the potential for this therapy, including fully human anti-CD19 CAR T cells and the possibility of its effect in multiple myeloma or solid tumors.

Can you tell us about anti-CD19 CAR T cells?

Anti-CD19 CAR-T cells are a gene therapy approach to treating lymphoma and leukemia that started several years ago now. At the National Cancer Institute (NCI) we opened our first trial in 2009. Since that time we and other groups have continued to develop anti-CD19 CAR T cells as therapy for a variety of B-cell malignancies.

The main thrust of our research is using the patient’s own T cells as a treatment for lymphoma. Since 2009, we’ve treated at the NCI, on our first protocol, 43 patients with lymphoma and chronic lymphocytic leukemia. The general process we use is to have the patient come in and get an apheresis which gives us the peripheral blood mononuclear cells to take to the lab and then genetically engineer those cells to express an anti-CD19 chimeric antigen receptor (CAR). After the cells are collected, the patient comes in and gets some chemotherapy. The chemotherapy is given to enhance the activity of the CAR T cells.

Many investigators have found in mouse models and fairly strong evidence in humans that giving chemotherapy before these CAR T cells enhances the activity of the CAR T cells and increases the chances of remissions. Shortly after that they get their infusion of CAR T cells. After the infusion we require the patients to stay in the hospital for several days at the National Institutes of Health (NIH). It can be anywhere from eight days to 10 days in the hospital. It could be even longer if the patients have toxicity.

What are some of the toxicities seen from this treatment?

There’s a syndrome called cytokine release syndrome which is caused by cytokines being released from the T cells when they contact the lymphoma or leukemia and this causes most prominently fever, tachycardia and hypotension. It can also cause things like abnormalities of blood coagulation, abnormalities in liver tests and renal insufficiency, among other things. There are many other rarer toxicities that we see but those are the main cytokine release toxicities that we see.

Another prominent toxicity that we’ve had to deal with is neurologic toxicity. We have patients who develop things like aphasia, ataxia, confusion; some patients even have gone into comas. So all this toxicity is certainly a major effort with our future researchers to try and reduce that. But it is certainly something we have to let everybody know about - that it is a high risk treatment. It’s not completely safe, it is very experimental and all of our results are very early.

What are some developments and advancements that researchers have enacted?



Talk about this article with other patients, caregivers, and advocates in the Lymphoma Cancer CURE discussion group.
x-button
Special Feature
Share Your Art
Related Articles
3 Times Cancer Was Fun
Cobra, baseball cards and two guys who always let me know I wasn't dead.
CAR T-Cell Therapy Yescarta Approved to Treat Non-Hodgkin Lymphoma
Yescarta was granted FDA approval for use in adults with relapsed or refractory non-Hodgkin lymphoma. This is only the second CAR T-cell therapy ever approved.
Expert Talks Treating Newly Diagnosed Patients With Myeloma
The way that newly diagnosed patients with multiple myeloma is treated has changed significantly over recent years, especially as new drugs moved into the treatment realm for the disease, says Shaji K. Kumar, M.D.  
Related Videos
Cancer Survivor Celebrates by Dancing with Scripps Doctor
Irene Hutchins, M.D., and her patient Steve Valentine, both accomplished ballroom dancers, made a pact to dance together once he had recovered from late-stage Burkitt lymphoma. They performed their victory dance June 11 during Cancer Survivors Day at Scripps Green Hospital, in La Jolla, California, where Hutchins treated Valentine.
Moving Mountains for Multiple Myeloma Kilimanjaro 2017
‚ÄčA team of patients, researchers, advocates and loved ones climbed Mount Kilimanjaro, Africa's highest mountain, to raise money for multiple myeloma awareness and research, benefitting the Multiple Myeloma Research Foundation.
MM4MM 2017 Kilimanjaro Team Training Climb
This year, a group of patients, advocates and health care professionals will tackle Mount Kilimanjaro to raise money and awareness for multiple myeloma.   
x
//For side ad protocol