Researchers may have uncovered a novel strategy to identify which patients may experience poorer outcomes from chimeric antigen receptor (CAR) T-cell therapy prior to treatment, according to a recent study published by Faramand et al in Blood Cancer Discovery. The findings indicate opportunities to improve the safety and efficacy of CAR T-cell therapy.
Background
As new cancer therapies become available, researchers are determining methods to optimize approaches so that more patients can benefit from groundbreaking treatments.
CAR T-cell therapy—which enables patients’ immune cells to target and eradicate cancer cells—has been approved by the U.S. Food and Drug Administration for the treatment of hematologic malignancies, including some types of lymphoma, leukemia, and multiple myeloma. However, these treatments have been associated with significant and severe side effects.
“[CAR] T-cell therapy has changed the treatment paradigm for patients with relapsed/refractory hematologic malignancies. Despite encouraging efficacy, a subset of patients have [experienced] poor clinical outcomes. We show that a simple clinically applicable model using pre-lymphodepletion [C-reactive protein] and ferritin can identify patients at high risk of poor outcomes,” the study authors revealed.
While previous studies have explored ways to characterize and measure the effectiveness of CAR T-cell therapy, there have not been any widely available laboratory tests or biomarkers to rapidly identify patients at high risk for poor outcomes prior to therapy.
Study Methods and Results
In the recent study, the researchers recruited 146 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who had been treated with the CAR T-cell therapy axicabtagene ciloleucel and had already received at least two prior lines of therapy for lymphoma. The researchers noted that following CAR T-cell therapy, 93% of the patients experienced cytokine-release syndrome and 61% of them developed immune effector cell–associated neurotoxicity syndrome.
They found that the patients with baseline C-reactive protein levels in the serum blood of at least 4 mg/dL and ferritin levels of 400 ng/mL or higher were at highest risk for experiencing poor outcomes such as reduced progression-free and overall survival as well as higher rates of severe toxicities. The researchers also documented two independent international cohorts that validated their novel approach, demonstrating that patients classified as low risk may have positive efficacy and safety outcomes.
Conclusions
“We determined that two common and easily measured blood tests can identify in advance which patients are at high risk for poor outcomes after treatment with CD19-targeted CAR T cells. We’re excited because these findings not only help us to make CAR T-cell therapies work for more patients with hard-to-treat cancers, they also help us spare some patients from additional medications they don’t need,” said co–senior study author Marco Davila, MD, PhD, Senior Vice President and Associate Director for Translational Research at the Roswell Park Comprehensive Cancer Center. “Our algorithm allows us to identify patients who would be good candidates for prophylaxis, or additional therapies to control and prevent side effects, or for clinical studies to improve their outcomes. It’s an important tool that will help us personalize treatment for each patient,” he underscored.
“Our group has previously shown that systemic inflammation and suppressive myeloid cells are associated with decreased efficacy in CAR T-cell therapy for lymphoma. Here we demonstrate that simple, and widely available, laboratory tests can similarly predict those patients with a decreased chance for success with CAR T-[cell therapy]. New strategies are needed for these patients, although [this treatment] remains the best therapeutic option for most patients we studied,” concluded co–senior study author Frederick Locke, MD, Chair of the Department of Blood and Marrow Transplant and Cellular Immunotherapy at the Moffitt Cancer Center.
Disclosure: The research in this study was supported by a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health and by the Rustum Family Endowed Chair in Translational Research through the Roswell Park Alliance Foundation. For full disclosures of the study authors, visit aacrjournals.org.
