Patients with large B-cell lymphoma who have relapsed or have “refractory” disease, meaning they don’t respond to standard therapies, typically have poor outcomes, particularly if they are not eligible for stem-cell transplant due to their age and/or co-existing diseases. But thanks to positive results from an immunotherapy trial that Atrium Health Levine Cancer Institute (LCI) contributed to, these patients will soon have a new and cutting-edge treatment option.
The trial tested the CAR-T cell therapy Breyanzi (liso-cel) in patients with relapsed or refractory large B- cell lymphoma after failure of front-line chemoimmunotherapy, who were not intended for transplant. Nilanjan Ghosh, MD, PhD, chair of LCI’s department of hematologic oncology and blood disorders and chief of the lymphoma division, was one of the trial investigators. He coordinated with researchers at the University of Pittsburgh Hillman Cancer Center, Johns Hopkins Cancer Center and several other academic institutions, as well as with Bristol Myers Squibb, which manufactures the CAR-T therapy.
Breyanzi was first approved by the Food and Drug Administration (FDA) in February 2021 for the treatment of adults with large B-cell lymphoma who had relapsed after two treatments. On June 24, the FDA approved the drug for earlier use as a second-line treatment of adults with the disease.
This form of medicine is a personalized treatment that’s made by removing T cells from patients and engineering them to be able to recognize and attack their own cancer cells. Among the 61 patients in the trial who received Breyanzi, the proportion of patients who had at least a partial response—was 80%, Ghosh reported during the recent conference of the European Hematology Association in Vienna. The median duration of response was 12 months. What’s more, 54% of patients had a complete response, meaning the cancer disappeared and responses were very durable in those patients who achieved a complete response. The median overall survival rate in the trial has not yet been reached because many of those patients are still alive and cancer-free nearly two years after receiving the treatment.
“This is a really good outcome,” Ghosh says. “Historically, we consider stem cell transplant as an opportunity for a cure, but many patients aren’t eligible because of age and/or comorbidities that make it difficult to tolerate the treatment. The tolerability of this treatment is quite good, and it could be an excellent second-line treatment option for these patients.”
A Boost to the Immune System
CAR-T treatments have greatly improved the prognosis for patients with some forms of blood cancer ever since the first one was approved by the FDA to treat leukemia in 2017. Breyanzi is now one of six CAR-T therapies on the market. The T cells that these therapies are made from act as soldiers of the immune system—they hunt down cancer cells and eliminate them. After T cells are collected from patients in a procedure called leukapheresis, they’re engineered to produce chimeric antigen receptors (CARs), which recognize proteins on the surface of cancer cells, allowing the T cells to find and destroy cancer cells.
CAR-T treatments can cause side effects, some of which are a concern in older people, particularly those with diseases that are common in the aged, such as heart and kidney disease. For example, an immune response called cytokine release syndrome (CRS) can occur, causing symptoms such as fever, low blood pressure and rash. The cell therapy can also cause neurological side effects like impaired cognitive or motor skills.
During the clinical trial, CRS was diagnosed in 38% of patients, most of whom had low-grade symptoms that were easily manageable with a drug called tocilizumab, which can be administered with or without steroids, Ghosh says.
“Only one patient needed more than one dose of tocilizumab to treat cytokine release syndrome,” he said. A more common side effect was neutropenia, or abnormally low levels of infection-fighting white blood cells. That was also easy to manage with use of growth factor, said Ghosh.
Managing Side Effects
The prospect of needing drugs to treat side effects of cancer treatments may be difficult for older patients to consider, given the fact that they may already be taking a lot of medicines to treat other diseases. But one key characteristic of CAR-T treatments makes them more tolerable than traditional cancer drugs and thus easier for older patients to manage side effects.
“When patients receive their CAR-T cells, that’s a one-time treatment,” Ghosh says.
The FDA approval signifies an important new choice for patients.
“I have high hopes for this,” says Ghosh. “If we can use it in patients who are eligible for bone marrow transplant, as well as in those who are ineligible, a broad range of patients will be able to benefit from CAR-T cell treatments.”
Learn more about CAR-T therapy at Levine Cancer Institute.
