Tumor Characteristics Predict Improved CAR-T Cell Therapy Outcomes

Yescarta, a CAR-T cell therapy, may provide better outcomes for patients with large B-cell lymphoma, research showed.

Certain tumor characteristics were associated with improved outcomes from the CAR-T cell therapy, Yescarta (axicabtagene ciloleucel), in patients with large B-cell lymphoma, according to findings recently published in Nature Medicine.

The researchers analyzed data from the phase 3 ZUMA-7 clinical trial, which led to the 2022 Food and Drug Administration approval of Yescarta for large B-cells lymphoma that did not respond to or returned after treatment with chemoimmunotherapy.

READ MORE:FDA Approves Yescarta, First CAR-T Cell Therapy, for Patients With Large B-Cell Lymphoma That Has Failed Initial Treatment

Yescarta is a CAR-T cell therapy, which is a type of treatment that works by taking a patient’s blood, engineering their immune T cells to find and fight cancer, growing said cells, and then infusing them back into the patient.

In recent years, these drugs have drastically improved outcomes for patients with blood cancer, there is still a group of patients who either do not respond well to CAR-T cell therapy, or experience disease relapse shortly after. That said, studies like these, which may help indicate which patients are more likely to do better or worse on CAR-T cell therapy, are essential.

“Knowledge of the immune contexture is essential for understanding mechanisms of action and likelihood of prolonged response to CAR-T cell therapy. Collectively, these data may help inform studies evaluating patient management based on tumor biology and biomarkers, as well as the design of next-generation therapeutics,” study author, Dr. Frederick L. Locke, chair of the Blood and Marrow Transplant and Cellular Immunotherapy Department at Moffitt Cancer Center, said in a press release issued by Moffitt.

Findings showed that B-cell gene expression signature and CD19 expression were significantly associated with improved event-free survival (time when patients live that their cancer does not come back or get worse) and duration of response for patients who received Yescarta, but not for those who underwent standard-of-care salvage chemotherapy. Notably, Yescarta works by targeting the CD19 molecule that is found on large B-cell lymphoma cells.

The tumor biomarkers that were associated with improved outcomes to Yescarta tended to decrease as patients underwent more lines of therapy, which, according to the release, could pose an argument for moving Yescarta up to earlier lines of therapy to potentially improve outcomes.

The researchers wrote in their study, “Altogether, because of favorable tumor characteristics and T-cell fitness, it is possible that (Yescarta) would present a further improved therapeutic profile in first-line therapy,” noting that these findings are consistent with other research — namely the ZUMA-12 study, which showed that when given as a frontline therapy to patients with high-risk large B-cell lymphoma, Yescarta resulted in a 78% complete response rate (percentage of patients whose disease disappeared from treatment) and an 89% response rate (percentage of patients whose disease shrunk or disappeared).

The researchers also observed that regardless of patients’ B-cell gene expression signature and CD19 expression, outcomes were better in the Yescarta group compared to the standard-of-care group. Specifically, Yescarta reduced the risk of disease progression and the need for new therapy or death by 60% compared to standard-of-care therapy.

Additionally, the researchers noted that patients with a high tumor burden or elevated levels of the lactate dehydrogenase enzyme tended to have shorter event-free survival when taking the standard chemotherapy, but not Yescarta. According to the press release on the findings, this could be “suggesting (Yescarta) may overcome some mechanisms of resistance to standard therapy.”

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