CHICAGO – The latest results of clinical trials utilizing a personalized cellular therapy developed by a team from the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania will be presented today during the annual meeting of the American Society of Clinical Oncology in Chicago's McCormick Place.
The new results – from trials for patients with advanced lymphoma, multiple myeloma, and pancreatic cancer – expand on Penn’s work with chimeric antigen receptor (CAR) therapies, building on findings in patients with chronic lymphocytic leukemia and acute lymphoblastic leukemia dating back to the start of the first clinical trial in 2010.
Highlights of the new data include:
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Thirteen of 19 patients with two types of non-Hodgkin lymphoma, diffuse large B cell lymphoma (DLBCL) and follicular lymphoma (FL), responded to the therapy. Eleven patients experienced complete responses to the therapy, and two had partial responses, including a 100 percent response rate (six complete responses and one partial response) among the patients with follicular lymphoma who received the therapy. Results indicated that in some patients, the engineered cells continued attacking their cancer over time: Six patients with partial responses at three months after receiving the therapy continued to have tumor shrinkage and became complete responders when assessed at six months. Two patients with partial responses subsequently experienced progression of their cancer, at 6 and 12 months after therapy. Median follow-up for the DLBCL patients is 274 days; median follow-up for the FL patients is 290 days. (Abstract #8516)
- Responses in four of five patients (two complete responses and two partial responses) with multiple myeloma who received the therapy. Patients treated as part of this trial have been followed between one and 11 months, with two patients progressing during this time period. The first patient treated remains in complete remission. (Abstract #8517)
- In a group of six patients with advanced pancreatic cancer who were treated with CAR T cells engineered using RNA, results included stable disease for 3.7 and 5.3 months in two patients, and stable or decreased metabolic activity in the tumors of four patients. One patient experienced a complete loss of metabolic activity in all tumors in the liver within 28 days after treatment. The authors believe the results may point to the safety and potential utility of CAR T cells being used to treat a solid cancer. The investigators used a novel RNA-based approach to engineer CAR T cells to recognize mesothelin, a protein overexpressed on pancreatic cancer cells, but also expressed on some normal tissues. This trial enabled the testing of this CAR target for pancreatic cancer before beginning a new study that utilizes a lentiviral-engineered CAR to produce stable CAR expression in T cells. (Abstract #3007)
Three patients (two with lymphoma and one with myeloma) who received the experimental T cell therapy developed a cytokine release syndrome (CRS) within several weeks after their infusions, which included varying degrees of flu-like symptoms, with high fevers, nausea, and muscle pain. Other side effects observed included kidney problems, abdominal pain, hypertension and hypotension. Prior CAR studies have shown that CRS can be a very serious and life-threatening toxicity.
This experimental personalized cellular therapy approach begins with each patient’s own immune cells, collected through a procedure similar to dialysis. The cells are then engineered in a laboratory and infused back into the patient after being trained to hunt and kill their cancer cells. The engineered cells contain an antibody-like protein known as a chimeric antigen receptor (CAR), which is designed to bind to a target on the surface of cancer cells. For example, Penn’s blood cancer trials employ a CAR targeting the protein CD19, which is found on the surface of B cells, including the cancerous B cells that characterize several types of leukemia and lymphoma. The modified “hunter” cells are then infused back into the patient's body, where they multiply and are believed to attack the cancer cells. A signaling domain built into the CAR promotes rapid multiplication of the modified cells that tests reveal can grow to more than 10,000 new cells for each single engineered cell patients receive.
All patients who enroll in these trials have cancers that have progressed despite multiple conventional FDA-approved therapies. Patients in the lymphoma and myeloma clinical trials receive lymphodepleting chemotherapy prior to infusion of the modified cells, and the myeloma patients also receive an autologous stem cell transplant.
The lymphoma trial is led by Stephen Schuster, MD, the Robert and Margarita Louis-Dreyfus Associate Professor in Chronic Lymphocytic Leukemia and Lymphoma Clinical Care and Research. The myeloma trial is led by Edward Stadtmauer, MD, Chief of Hematologic Malignancies and a professor of Hematology/Oncology, and Alfred Garfall, MD, an instructor of Hematology/Oncology, will present their results. Gregory Beatty, MD, PhD, an assistant professor of Hematology/Oncology, will present the pancreatic cancer trial results. Carl June, MD, the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine and director of Translational Research in the Abramson Cancer Center, leads Penn’s basic and clinical research testing these CAR-based approaches.
Other clinical trials utilizing CAR technology are currently underway at Penn for the treatment of chronic lymphocytic leukemia, acute lymphoblastic leukemia, mesothelioma and ovarian and brain cancer.
Funding sources for the trials include the National Institutes of Health (K12 CA076931), Novartis, the Cancer Research Institute and the Lustgarten Foundation.
Schuster and Garfall will present their findings in the Chimeric Antigen Receptor T Cell Therapy for B-Cell Malignancies Clinical Science Symposium on Monday, June 1 from 3 p.m. to 4:30 p.m. CST in McCormick Place’s E Aerie Crown Theater. Beatty will present his results in the Developmental Therapeutics—Immunotherapy oral abstract session on Monday, June 1 from 1:15 p.m. to 4:15 p.m. in McCormick Place S406.
Editor’s Note: The University of Pennsylvania has licensed technologies involved in this trial to Novartis. Some of the scientists involved in these trials, including Dr. June, are inventors of these technologies, As a result of Penn-Novartis licensing relationship, the University of Pennsylvania receives significant financial benefit and the Penn inventors are benefitting financially.
Penn Medicine is one of the world’s leading academic medical centers, dedicated to the related missions of medical education, biomedical research, excellence in patient care, and community service. The organization consists of the University of Pennsylvania Health System and Penn’s Raymond and Ruth Perelman School of Medicine, founded in 1765 as the nation’s first medical school.
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