Historically, people with certain types of lymphoma haven’t had many options when standard therapies didn’t work for them. Now, developments in a type of immune therapy called chimeric antigen receptor (CAR) T-cell therapy are showing that when lymphoma is treated with CAR T-cell therapy, patients may be able to achieve prolonged remission – periods of time when signs and symptoms of cancer are reduced or have disappeared.
Essentially, CAR T-cell therapy “trains” a person’s own immune cells to kill their cancer. It works like this: special immune cells called T cells are extracted from a person’s blood and sent to a lab, where they are re-engineered to become more powerful and “instructed” to identify and kill lymphoma. The new T cells are then infused back into the patient’s bloodstream, where they go to work fighting the cancer. Different types of CAR T-cell therapy are available not just for lymphoma, but also for leukemia and myeloma.
On Oct. 5, 2020, Medical College of Wisconsin (MCW) researchers shared the results of their Phase I clinical trial exploring CAR T-cell therapy for non-Hodgkin lymphoma in the medical journal Nature Medicine (Vol. 26, pages1569–1575(2020)). A Phase I trial tests a new drug or treatment in a small group of people (20-80) for the first time to ascertain safety, maximum tolerated dose, safe dose range and side effects. In the trial, researchers tested a first-in-the-world CAR T-cell approach that targeted two proteins (antigens CD19 and 20) on the surface of cancer cells rather than one. It was studied and developed at MCW.
Parameswaran Hari, MD, MS, the senior author of the paper, specializes in treating lymphoma, leukemia and myeloma. The study’s principal investigator is Nirav Shah, MD, a specialist in lymphoma and stem cell transplantation.
Success Rate of CAR T-Cell Therapy in Phase I Clinical Trial
CAR T-cell therapy has been in development in the U.S. since 2012 but doctors at the Froedtert & the Medical College of Wisconsin Clinical Cancer Center at Froedtert Hospital were the first to treat patients using a double-targeted CAR T-cell approach.
The clinical trial involved people who had not had success with standard treatment such as chemotherapy for their relapsed or refractory B cell non-Hodgkin lymphoma, a cancer involving the immune system. Relapsed means the cancer got better with initial treatment but then returned. Patients with refractory disease had cancer that did not respond to treatment at all.
Within 28 days of being treated with CAR T-cell therapy, 82% of trial patients responded positively – with more than half of them still in remission six months later. With a higher dose of therapy, responses were improved.
Dr. Shah called results of the first trial “a giant leap forward in personalized medicine.” Pioneers in the field of immunotherapy, Dr. Shah and other MCW researchers have a long history of exploring ways to harness the body’s own immune system to fight cancer cells. Their work represents an alternative to traditional chemotherapy, radiation therapy and stem cell transplants. These treatments are often effective in killing cancer cells but can damage the body’s healthy cells.
Within 28 days of being treated with CAR T-cell therapy, 82% of lymphoma trial patients had a positive response.
Paving the Way for National CAR T-Cell Immunotherapy Research
Launching the phase I trial was the result of decades of collaborative cancer and cellular immunotherapy research within the Froedtert & MCW Blood and Marrow Transplant and Cellular Therapy Program. It paved the way for national studies of CAR T-cell therapy.
Now, a larger (Phase II) trial involving multiple institutions around the country is being rolled out to better understand the therapy’s effectiveness and how nuances of the treatment process may result in excellent outcomes for a larger group of patients. It will also study the how a higher therapy dose is related to prolonged remission. A Phase II trial tests a drug or treatment with a larger group of people to see if it is effective, safe and to gather more information about a safe dose range.
A special self-contained desktop device called the CliniMACS Prodigy®, developed by Miltenyi Biotec, allows the MCW CAR T-cell therapy team to process a patient’s T-cells into new “super-charged” cells that are ready to infuse back into a patient’s bloodstream within 14 days, where they go to work eliminating cancer. This lab work is performed on the Froedtert Hospital campus, saving precious time for patients. Available commercial CAR T products require freezing T cells and shipping them to and from an out-of-state lab, so it can take longer to manufacture CAR T-cells.
The encouraging results of the trial published in Nature Medicine are paving the way for more effective and efficient treatment options. Very few cancer centers offer the combination of resources and high level of personalized medicine knowledge and expertise available at the Froedtert & MCW Clinical Cancer Center.
“We are constantly harnessing our accumulated knowledge to improve outcomes for our patients,” Dr. Hari said. “There is amazing potential here for the future treatment of not just lymphoma but also other types of blood cancer like myeloma and eventually, solid tumors like breast cancer.”
This research was made possible through the philanthropic dollars raised by Drive Fore a Cure, the Children’s Wisconsin Foundation and the MACC Fund (Midwest Athletes Against Childhood Cancer, Inc.), and their support of the Cell Therapy Lab at MCW.