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FDA Approves ‘Living Drug’ for Treatment of Aggressive Blood Cancer

Sylvester Comprehensive Cancer Center is one of a very limited number of sites in the United States that will provide a newly approved innovative treatment for diffuse large B cell lymphoma — an aggressive form of blood cancer.

A patient’s T cells are transformed through state-of-the-art genetic engineering into supercharged cancer-hunting cellular therapy.

The Food and Drug Administration approved the immunotherapy last week; it takes a patient’s own immune cells (T cells), and uses state-of-the-art genetic engineering to transform them into a supercharged cancer-hunting cellular therapy. Because of the potential for serious side effects, only cancer centers with the expertise to administer the therapy will be part of the initial rollout.

The new treatment, called Yescarta (axicabtagene ciloleucel), was developed by Kite Pharma, Inc. It is approved for use in patients whose cancer has not responded to standard therapies. Patients whose lymphoma has recurred after at least two different forms of treatment are eligible. Standard treatments for the disease include chemoimmunotherapy and stem cell transplantation, which may still be required before or after Yescarta.

Sylvester is one of the 22 institutions in the United States that took part in the study that led to FDA approval. Lazaros J. Lekakis, M.D., a hematologic oncologist at Sylvester, was the principal investigator for the trial at the cancer center.
According to the published results, 39 percent of the 111 patients who participated nationwide achieved a complete remission, representing an important demonstration of the efficacy of the newer cellular therapies against previously untreatable cancers.

“This revolutionary therapy involves the reengineering of the patients’ own lymphocytes to transform them into ‘killer’ cells which can recognize and destroy lymphoma cells,” said Lekakis. “The therapy has significant efficacy and offers an exciting option for patients in whom standard therapy has failed.”

A new hope comes with risks
Krishna Komanduri, M.D., director of the UM Stem Cell Transplant and Cellular Therapy program and president of the American Society for Blood and Marrow Transplantation, emphasizes that CAR?T?cell therapy is extremely promising but it is associated with unique acute toxicities, which can be severe or even fatal.

“This is why it is so important that only doctors who are specially trained administer this treatment,” said Komanduri, who monitored the participants in the trial and also co-authored a paper on how to assess and manage the toxicities.

Axicabtagene ciloleucel can cause two types of potentially dangerous reactions, according to Komanduri. The most commonly observed toxicity, Cytokine-release syndrome (CRS), is caused by an activated immune system that goes into overdrive, leading to symptoms that can include fever and can mimic the state of overwhelming infection. More serious forms of CRS, however, can lead to drops in blood pressure and organ failure.

The other more serious reaction is CAR-T-cell-related encephalopathy syndrome (CRES), which is characterized by a toxic encephalopathic state with symptoms of aphasia and confusion, with seizure-like states observed in some patients. A subset of patients with CRES may even develop cerebral edema, which can be fatal in rare cases.

“Accurate assessment and prompt management of CRS and CRES can mitigate the risk associated with these promising immunotherapies that provide hope for patients whose cancer had not responded to therapy, and the expertise in cellular therapy and toxicity management is a key reason these therapies should, in the short term, be restricted to centers with the greatest expertise and experience,” said Komanduri.

More therapies on the horizon
The FDA approval further demonstrates that the immune system is a new frontier in cancer therapies, and Sylvester is leading the way. Current trials are using genetically engineered T cells in hematologic malignancies, such as mantle cell lymphoma, follicular lymphoma, and acute lymphoblastic leukemia, as well as in solid tumors, such as ovarian cancer, sarcoma and non-small cell lung cancer. A similar CAR-T therapy approved by the FDA in September for use in children and young adults with B-cell acute lymphoblastic leukemia will likely be available at the center in the coming year.

“CAR-T and other cellular therapies represent an important step forward in our ability to target cancer cells, which will have broad applicability,” said Joseph D. Rosenblatt M.D., chief of the Division of Hematology-Oncology at UM.

Tags: axicabtagene ciloleucel, diffuse large B cell lymphoma, Joseph D. Rosenblatt, Kite Pharma, Krishna Komanduri, Lazaros J. Lekakis, Miller School of Medicine, Sylvester Comprehensive Cancer Center, University of Miami, Yescarta