Secondary Cancers May Reduce Long-Term Survival After Yescarta in Lymphoma

Short-term outcomes following treatment with Yescarta (axicabtagene ciloleucel) for patients with B-cell lymphoma are reported to be promising, but long-term data regarding survivorship is still commonly unknown.

Yescarta is a CAR-T cell therapy — a type of immunotherapy — that is commonly used to treat patients with B-cell lymphoma that returned or did not improve after treatment with at least two previous lines of systemic therapy, according to the National Cancer Institute.

The treatment was approved by the Food and Drug Administration in April 2022 for patients with B-cell lymphoma after a lack of responses to initial treatment. CAR-T cell therapy works when doctors first draw patients’ blood to extract immune T cells. These cells are then engineered to target and destroy the cancer cells, and are then infused back into the patient to treat their cancer.

READ MORE: Tumor Characteristics Predict Improved CAR-T Cell Therapy Outcomes

A study published in the Journal of Clinical Oncology noted that although Yescarta has promising short-term data, long-term data regarding survivorship is not as commonly known. In particular, the study found that late infections and the development of secondary cancers may reduce long-term survival after patients receive CAR-T cell therapy, especially in older patients.

This study, which was led by researchers from Moffitt Cancer Center in Tampa, Florida, included 275 patients, who received standard-of-care Yescarta after two or more lines of treatment, with a median follow-up of 12.9 months.

Among the included patients, the progression-free survival (PFS; time patients live without their disease worsening or spreading) at five years was 29%. The overall survival (OS; time patients live, regardless of their disease status) was 40% at five years, the researchers established.

“Our research shows that [Yescarta] can provide durable, long-lasting responses in a substantial portion of patients with relapsed or refractory large B-cell lymphoma,” Dr. Michael Jain, lead study author and associate member of the Blood and Marrow Transplant and Cellular Immunotherapy Department at Moffitt, said in a news release about the study. “This is noteworthy given the limited options available for these patients previously.”

Of note, the researchers found that patients who were aged 60 or older had a lower risk of relapse (the cancer returning). Still, these respective patients showed a higher risk of non-relapse mortality (death not caused by relapse), compared with patients younger than age 60.

Researchers reported that non-relapse mortality was mostly because of infections and secondary cancers. These occurred in 24 patients, which included therapy-related myeloproliferative neoplasms (MPNs; type of blood cancer in stem cells in the bone marrow) in 15 patients, solid tumors in seven patients and unrelated lymphoid malignancies (cancer in the lymphatic system) in two patients.

At five years, the non-relapse mortality was 16.2%, in which the researchers noted that more than half of these non-relapse moralities occurred beyond two years.

“This study highlights the importance of personalized follow-up care and proactive management of potential complications,” Jain said in the release. “Our goal is to enhance patients’ long-term quality of life receiving CAR-T cell therapies.”

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