Ahmed Galal, MD, instructor, Department of Medicine, Duke Cancer Institute, discusses the management of adverse events (AEs) associated with CAR T-cell therapy.

When CAR T-cell therapy was first introduced to the field of non-Hodgkin lymphoma, there was a lot of concern over potential AEs and how to treat them, says Galal. Steroids were the predominant method of treatment since they could affect the CAR T cells by decreasing their activity. Steroids continue to be used to treat patients who develop AEs that manifest as a result of this approach.

Now, steroids are being used even earlier on to treat these patients when they show early signs of cytokine release syndrome (CRS). Even so, most AEs are discovered at the grade II level. The hope is that increased awareness will shift the field toward less grade 3/4 neurotoxicity, says Galal. Additionally, a lot of research is devoted to enhancing the product itself, and in doing so, decrease CRS and neurotoxicity. Currently, researchers are working on developing “on and off switch” for CAR T-cell therapy.

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Dr. Galal on Managing AEs Linked With CAR T-Cell Therapy

Ahmed Galal, MD, instructor, Department of Medicine, Duke Cancer Institute, discusses the use of CAR T-cell therapy in patients with relapsed/refractory lymphomas.

CAR T-cell therapy is currently FDA-approved for patients with aggressive lymphoma subtypes, such as diffuse large B-cell lymphoma, primary mediastinal lymphoma, and other high-grade lymphomas. These patients are typically eligible for CAR T cell-therapy after having developed resistance to prior 2 lines of treatment. Galal says that approximately 40% of patients will progress on frontline R-CHOP (rituximab [Rituxan], cyclophosphamide, doxorubicin, vincristine, and prednisone) or R-EPOCH (rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride), and only 30% of those patients will benefit from an autologous stem cell transplant. Thus, CAR T cells can make a difference in a fairly large population of patients that had once represented an unmet need.

This approach has provided new hope for these patients in the third-line setting, he concludes.

Dr. Galal on CAR T-Cell Therapy in Relapsed/Refractory Lymphomas

Ahmed Galal, MD, instructor, Department of Medicine, Duke Cancer Institute, discusses ways of extending the reach of CAR T-cell therapy in real-world practice.

Real-world evidence suggests that patient selection should be optimized so that more of those who are eligible to receive CAR T-cell therapy can, says Galal. For example, there are approximately 12,000 patients in the United States with relapsed/refractory diffuse large B-cell lymphoma who are eligible to receive the therapy; however, to date, only approximately 1,000 patients have been treated with this approach, he adds. To improve upon this, providers must identify and refer potential candidates earlier on in their treatment course.

Secondly, there are many financial barriers that prevent widespread access to eligible patients, says Galal. In terms of response rates, physicians have to figure out how to extend the persistence of CAR T cells, as many patients will relapse shortly after receiving their transfusion. Additionally, cytokine release syndrome is a common adverse event associated with the therapy that, if circumvented, would increase the feasibility of this approach, concludes Galal.

Ahmed Galal, MD

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Dr. Galal on Managing AEs Linked With CAR T-Cell Therapy

Dr. Galal on CAR T-Cell Therapy in Relapsed/Refractory Lymphomas

Dr. Galal on Ways of Extending the Reach of CAR T-Cell Therapy