CAR T Cell Therapy Comes to UPMC Children’s

December 27, 2019

Chimeric Antigen Receptor T cell (CAR T cell) therapy has proven to be, for a subset of patients and diseases, a revolutionary, curative, and durable therapy.

UPMC Children’s Hospital of Pittsburgh began preparations for performing CAR T cell infusions for select pediatric patients in late 2017, with live administrations of the therapy beginning in February of this year. UPMC Children’s is currently treating pediatric and young adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-cell ALL) up to the age of 25, with Kymriah® from Novartis.

Randy Windreich, MD, clinical director and fellowship director in the Division of Blood and Marrow Transplantation and Cellular Therapies, oversees the CAR T cell program at UPMC Children’s.

“Significant investment and infrastructure were needed to bring CAR T cell therapy to UPMC Children’s. Our Division, with the assistance and support of hospital administration, opted for the ability to do all the cell processing and counts on site, which dramatically speeds up the process for our patients,” says Dr. Windreich. 

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Dr. Windreich also notes that with the infrastructure now in place, UPMC Children’s will be in position to offer institutional clinical trials in CAR T cell, as well as participating with Children’s Oncology Group (COG) trials in the future and expanding patient access to potentially novel therapies.

As of the time of this writing, UPMC Children’s has treated three patients with CAR T cell infusions. The first two patients were children and the third a young adult, all of whom had relapsed and refractory B-cell ALL. All three patients went into the CAR T cell therapy with varying  amounts of leukemia still present, and at one month all were minimal residual disease (MRD) negative or in complete remission.

“Our first two patients have finally been able to achieve remission and sustain it for the last several months. Our third patient, who had perhaps the more difficult course, was also thrilled to hear that the CAR T cell worked and that he was in remission. So far, we are pleased with our initial results,” says Dr. Windreich. 

Managing the Complications of CAR T Cell: Cytokine Release Syndrome

As with any therapy, CAR T cell brings with it the potential for complications or patient reactions. One potentially severe and life-threatening complication of CAR T cell therapy is cytokine release syndrome (CRS). Essentially a massive, systemic inflammatory response, CRS poses a significant risk of morbidity and mortality.

Prior to opening CAR T cell therapy at UPMC Children’s, Dr. Windreich worked with staff from the pediatric intensive care unit (PICU) to develop a management algorithm for CAR T cell patients, essentially a set of instructions to help all staff manage these patients if or when CRS arises and at differing levels of severity. Hematology/oncology physicians, BMT physicians, advanced practice providers, PICU staff, emergency department staff, pharmacy, and nursing were trained in how to manage CRS in CAR T cell patients. Neurologists have also been incorporated into the training sessions because of the potential neurotoxicity with CAR T cell therapy.

“We invested significant time in the upfront training, but we also continue to do refresher training as well for new staff members in an ongoing manner. We also have made the information readily available on our internal website for the staff. Because months can go by without a CAR T cell case, we have to keep team members at the ready,” says Dr. Windreich.

Predicting who may end up with CRS or severe cases of it is ongoing. Right now, as Dr. Windreich explains, the best indicator is leukemia burden. The higher the initial burden, the higher the risk or severity of CRS. Other factors may be ongoing inflammation or infection, or other inflammatory states that could predispose patients to the complication.

Forward-Looking Perspectives on CAR T Cell Therapy

It ought to be obvious, but Dr. Windreich is hopeful that in the future CAR T cell therapies can be developed to target other types of leukemias and lymphomas, and even solid tumors for which it has so far shown little efficacy in other clinical trials and research around the country, although that work is progressing.

“It will be interesting to see if we can harness CAR T cell therapy or some variant of it in the future to treat the myeloid leukemias and T cell leukemias. It has so far proven very difficult to get a normal myeloid or T cell to recognize abnormal ones and mount a response, but I think we will eventually crack that code. Immunotherapies are the future right now. We need to work on expanding their abilities and efficacies for more diseases and more patients.”