Testing Cellular Therapy in Real-world Conditions

According to new findings, CAR T-cell therapy is safe and effective even for high-risk patients.

New therapies are often first tested under ideal conditions in studies of people with few complicating conditions.

“The ongoing joke is that you have to be an Olympic athlete to get on a clinical trial,” said Jay Y. Spiegel, M.D., a hematologist-oncologist at Sylvester Comprehensive Cancer Center at the University of Miami Miller School.

Such studies can provide a clean signal of whether the therapy works. But, they can also lead physicians to question whether the results are relevant for average patients with multiple health issues.

Spiegel and his colleagues are assessing this question in a study of patients treated with CAR T cells, a breakthrough treatment for several types of blood cancers.

“How is CAR T-cell therapy going to perform when we actually bring it to people who may not have been able to get on the initial trial?” he asked.  

The new retrospective study assessed long-term outcomes in patients with diffuse large B cell lymphoma (DLBCL), an often aggressive disease, treated with standard-of-care CAR T cells. The study included many patients with multiple pre-existing conditions.

The findings show similar response rates and overall survival as an earlier study that enrolled a healthier, highly selected set of patients.

The data should give physicians confidence that the CAR T-cell therapy works in real-world conditions in high-risk patients, said Dr. Spiegel. He presented the findings at the American Society of Hematology’s annual meeting on Monday, Dec. 11, in San Diego.

High-Risk Patients

T-cell therapy gains its power from the patient’s own immune system. It involves removing T cells from patients and reprogramming them to attack their cancer. The cells are then infused back into the patient.

“CAR T cells sort of revolutionized the treatment paradigm” for patients with advanced DLBCL and certain other blood cancers, said Dr. Spiegel.

Sylvester Comprehensive Cancer Center researcher Jay Spiegel
Jay Spiegel, M.D.

Before the advent of CAR T-cell therapy, DLBCL patients who relapsed or failed to respond to frontline treatments had few options.

In the new study, 275 such patients were infused with the CAR T-cell therapy axi-cel (axicabtagene ciloleucel) and evaluated after about five years. In addition to Sylvester, 16 other cancer centers participated in the study.

Patients had an overall survival rate of 40.3 percent at five years, reported Dr. Spiegel. In addition, 28.5 percent of patients survived without tumor progression.

The findings are comparable to response rates in an earlier clinical trial of axi-cel in a healthier patient population, leading to axi-cel approval. “We were encouraged by these results,” said Dr. Spiegel. “Often, results from clinical trials don’t translate to the larger population.”

The study also enabled the researchers to assess the causes of death in patients who did not succumb to DLBCL. “We were sobered by the rates of non-relapse mortality, and that is where we need to improve,” said Dr. Spiegel.

Patient Outcomes

Though CAR T cells can yield spectacular outcomes, the treatment may also increase patients’ vulnerability to other conditions. For instance, patients can be susceptible to infections due to immune suppression through the CAR T process.

In the new study, deaths not due to DLBCL relapse were mainly caused by infections, as well as secondary cancers. Physicians are working on ways to prevent such deaths.

Researchers are also assessing new types of CAR T cells that may be more effective against DLBCL and other cancers and yield fewer side-effects.

Sylvester is a good place to test cancer treatments in “real world” situations because of the diverse patient population in the Miami area, noted Dr. Spiegel.

“Before CAR T, we were looking for anything to help put a patient’s disease in remission if they failed chemotherapy,” said Dr. Spiegel. “Now, we’re focusing on survivorship outcomes and how we maximize the number of people we’re curing and get them to live longer and better.”

Tags: ASH2023, blood cancers, CAR T cells, Dr. Jay Spiegel, Sylvester Comprehensive Cancer Center