From OHC, Specialists in the Treatment of Adult Cancers and Blood Disorders
February 13, 2020
In 2018, OHC was the region’s first adult cancer group to offer chimeric antigen receptor T-cell therapy (CAR-T) to adults with blood cancers. This was a ground-breaking moment in the history of worldwide cancer care and OHC was at the forefront. So, where is CAR-T now? Is this game-changing approach to cancer treatment still working and is it here to stay? OHC’s James H. Essell, MD, a medical oncologist, hematologist and transplant specialist, answers these and other questions about the effectiveness and future of CAR-T.
Where are we now with CAR-T?
Dr. Essell: Today, there are two CAR-T therapies that are FDA-approved for use. They are approved to treat adults with relapsed large cell lymphoma and pediatric ALL. At OHC, we have seen patients that have been given only six months, then after CAR-T have complete remissions that are long-lasting and hopefully will be cured. Clinical trials are underway to move this therapy up. This means if these trials are successful, instead of waiting until the patient has tried all other options, they could receive CAR-T upon first relapse.
Why is that?
Dr. Essell: There are three challenges with CAR-T. The first is the issue of side effects or having a reaction to the treatment. The most common reaction is called cytokine release syndrome. Signs and symptoms of cytokine release syndrome include fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing. For most patients who experience a reaction to CAR-T, the reaction is mild. But sometimes, the reaction may be severe or life threatening. This is why initially all patients were treated in the hospital. OHC is participating in a national clinical trial to see if these treatments could be safely administered in the office.
The second challenge is relapse rate. A relapse occurs when the cancer comes back after treatment or does not go into remission. Those patients who enter into a complete remission have a high rate of cure. However, those that have a partial response or do not respond well as have limited survival. We retrain T-cells to attack a specific protein on the cancer cell. So, what does cancer do? It learns to live without that specific protein. Another reason is once CAR-T is administered and the T-cells have finished attacking the cancer, the number of T-cells left in the body has been reduced. If the cancer returns, there aren’t as many to attack its return.
The third challenge is expense. The process from start to finish is expensive. We have to collect cells from the patient, send them to a lab, there they are transformed into cancer fighting T-cells, expanded and then sent back to us to give to the patient. This process can take 3 – 6 weeks and is costly. And, sadly, some patients pass away or relapse before we can get the treatment.
How is OHC helping to overcome these challenges?
Dr. Essell: At OHC, we are participating in clinical trials to try to bring his treatment to the office where it is less expensive than in a hospital setting and using a new CAR T-cell that has fewer side effects. The hope is that both of these will allow more patients to be treated.
What are the two clinical trials?
Dr. Essell: One trial is for cancer patients with complex conditions. When we have a patient with aggressive B-cell non-Hodgkin’s lymphoma who relapse, the current standard of care in a stem cell transplant from a donor. If they are older or have organ dysfunction, they are not eligible for this treatment. Our research is evaluating a new CAR-T therapy called JCAR017, which has shown fewer side effects, so we think it could be ideal for cancer patients with other health challenges or are over the age of 70. Since JCAR017 has fewer side effects, the other trial is evaluating the safety of administering the treatment in an outpatient setting, like a treatment suite at an OHC office.
What about the issue of relapse?
Dr. Essell: There is a lot of work underway to make second-generation CAR T-cells. These, for example, may target two proteins on the cancer cell, making it harder for the cancer cells to transform and avoid detection from the attacking CAR T-cells. Another approach is to immunize the patient with a protein that is on the cancer cell to which the CAR T-cell is directed. In experimental studies, this is shown to maintain the high level of CAR T-cells and thus be available in the body to attack cancer if it returns. Finally, work is being done with CAR T-cells from a donor or cells that are available “off the shelf” without having to take time to manufacture the patient’s own cells.
What is the future of CAR-T?
Dr. Essell: One thing is certain, CAR-T is here to stay. It’s really an extension of immunotherapy which is being used for almost all cancers. We will see the day where chemotherapy is replaced by this immunotherapy, leading to higher cure rates and fewer side effects.
An example of this immune-therapy is the development of Bi-specific T-cell engagers, or BiTE technology. This approach also helps our body’s T-cells attack the cancer. What’s different is BiTE has real potential to be effective for both blood cancers and solid tumors. OHC anticipates opening clinical trials using BiTE in 2020.
How can people learn more?
James H. Essell, MD, is a medical oncologist and hematologist at OHC. Dr. Essell specializes in malignant and benign hematology, sarcoma, and blood and marrow transplantation. Dr. Essell serves as a principal investigator for hematologic malignant clinical trials at OHC. He serves as Chair, Cellular Therapy for The US Oncology Network and is the Medical Director of the Blood Cancer Center at The Jewish Hospital – Mercy Health.Comments (2)