Home » Blood Tests Could Predict Poor CAR T-Cell Therapy Outcomes

Blood Tests Could Predict Poor CAR T-Cell Therapy Outcomes

by Nikos Kokkorakis

Some of the most significant current research needs to focus on how to best utilize the new medicines for cancer when they become available in order to maximize the number of people who can receive these ground-breaking therapies. A group of collaborators from Roswell Park Comprehensive Cancer Center and Moffitt Cancer Center (New York, USA) have published work in Blood Cancer Discovery, a journal of the American Association for Cancer Research, that details the first method for determining which patients are most likely to have poor outcomes from CAR T-cell therapy prior to treatment, pointing to opportunities to enhance the safety and efficacy of this novel and quickly expanding class of cancer immunotherapies.

Despite encouraging outcomes with CAR T-cell therapy for hard-to-treat B-cell lymphoma, some patients experience toxicity and poor outcomes. The research from this group has shown that easily accessible laboratory tests for ferritin and c-reactive protein can determine which patients, prior to treatment, are most vulnerable to adverse events and are not responding to CD19-targeted CAR T-cell therapy. Even though CAR T-cell treatment shows promise in treating B-cell lymphoma, which is a difficult-to-treat cancer, some patients have poor results and toxicity.

The FDA has approved CAR T, or chimeric antigen receptor T-cell therapy, to treat a variety of blood malignancies, including multiple myeloma, leukemia, and some types of lymphoma. However, these novel therapies, which improve the ability of a patient’s immune system to recognize and destroy cancer cells, may come with serious, sometimes severe side effects.

The study, which was conducted on 146 patients who had previously undergone at least two lines of therapy for their lymphoma and were being treated with axicabtagene ciloleucel, also marketed as Yescarta, CAR T immunotherapy for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), is published in a recent publication. The majority of patients (61%) developed immunological effector cell-associated neurotoxicity syndrome (ICANS), and nearly all patients (93%) experienced cytokine release syndrome (CRS) after receiving CAR T.

The researchers came to the conclusion that patients who had baseline serum blood levels of 400 ng/mL or higher for ferritin and at least 4 mg/dL for c-reactive protein (CRP) were the most likely to have poor outcomes, such as higher rates of severe toxicities and reduced overall and progression-free survival.

A lab test or biomarker that might rapidly identify patients at high risk of poor outcomes before to CAR T-cell infusion was not previously widely available, despite the fact that numerous research have looked into ways to characterize and assess the effectiveness of CAR T therapy after treatment.

Moffitt Cancer Center served as the treatment facility for all 146 study participants. The approach has been validated by two independent worldwide cohorts, as documented by the authors. The results show that patients who are classed as low-risk experience outstanding safety and efficacy outcomes.

Reference: Faramand RG, Lee SB, Jain MD, et al. Baseline serum inflammatory proteins predict poor CAR T outcomes in diffuse large B-cell lymphoma. Blood Cancer Disc. 2024. doi: 10.1158/2643-3230.BCD-23-0056

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