Simple Blood Protein Tests Predict CAR T Outcomes for Lymphoma Patients

CAR T, or chimeric antigen receptor T-cell therapy, has been FDA-approved for various blood cancers such as certain types of lymphoma, leukemia, and multiple myeloma. While this innovative therapy enhances a patient’s immune cells' ability to target and eliminate cancer cells, it is often linked with significant and occasionally severe side effects. Now, a research team has discovered that two routine and easily conducted blood tests can predict which patients face a higher risk of adverse outcomes following treatment with CD19-targeted CAR T cells. This finding offers a chance to enhance the safety and effectiveness of this rapidly evolving category of cancer immunotherapies.

The study by a team of collaborators from Roswell Park Comprehensive Cancer Center (Buffalo, NY, USA) and Moffitt Cancer Center (Tampa, FL, USA) involved 146 patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). These patients, having previously undergone at least two prior lymphoma therapies, were treated with the CAR T immunotherapy axicabtagene ciloleucel (also known as axi-cel, and marketed as Yescarta). A significant majority of these patients (93%) experienced cytokine release syndrome (CRS) post-CAR T treatment, and over half (61%) developed immune effector cell-associated neurotoxicity syndrome (ICANS).

The researchers identified that patients with baseline serum blood levels of c-reactive protein (CRP) at or above 4 mg/dL and ferritin levels of 400 ng/mL or higher are at the greatest risk of poor outcomes. This includes reduced progression-free and overall survival, as well as elevated rates of severe toxicities. While numerous studies have focused on characterizing and assessing the effectiveness of CAR T therapy post-treatment, there was previously no readily accessible lab test or biomarker to quickly pinpoint patients at high risk for adverse outcomes before receiving CAR T-cell infusion.

“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,” said Marco Davila, MD, PhD, Senior Vice President and Associate Director for Translational Research at Roswell Park. “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.”

“Despite encouraging outcomes with CAR T-cell therapy for hard-to-treat B-cell lymphoma, some patients experience toxicity and poor outcomes. Our work determined that readily available lab tests for c-reactive protein and ferritin can identify which patients, pre-treatment, are at high risk for side effects and not responding to CD19-targeted CAR T-cell therapy,” added Rawan Faramand, MD, Assistant Member of the Blood and Marrow Transplant and Cellular Immunotherapy Department at Moffitt Cancer Center.

Related Links:
Roswell Park Comprehensive Cancer Center
Moffitt Cancer Center

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