Expert Explains Yescarta Label Update in CNS Lymphoma

In an interview with CURE, Dr. Lakshmi Nayak, a neuro-oncologist at Dana-Farber Cancer Institute and director of the Center for CNS Lymphoma, said the FDA’s recent update to Yescarta’s prescribing information expands access for patients with relapsed or refractory primary central nervous system lymphoma.

Primary CNS lymphoma is a rare and aggressive cancer with no FDA-approved treatments specific to the disease. While some patients respond to high-dose methotrexate-based chemotherapy, 50% to 60% experience recurrence within two years and 10% to 15% do not respond.

Earlier CAR-T trials excluded patients with CNS involvement due to concerns about neurotoxicity. However, a phase 1 study showed Yescarta was as safe in CNS lymphoma as in systemic lymphoma and demonstrated high efficacy in this hard-to-treat population.

Transcript

With the FDA removing the previous limitation on the use of Kite Pharma’s Yescarta, what does this change practically mean for patients with relapsed or refractory primary central nervous system lymphoma who may not have qualified before?

To answer that question, I’ll first go into a bit more detail about primary CNS lymphoma. This is an extremely rare and aggressive cancer of the nervous system, and historically there have been very limited treatment options. In the last several years, there has been optimization of chemotherapeutic regimens, which has led to better outcomes. That being said, there are currently no FDA-approved treatments specifically for this disease.

Although some patients do respond to chemotherapy-based regimens, the risk of recurrence is very high — about 50% to 60% within the first two years. Additionally, about 10% to 15% of patients do not respond at all to chemotherapy, which is primarily high-dose methotrexate-based regimens. So there is clearly an unmet need in this population in terms of improving patient outcomes.

With regard to CD19-directed CAR T-cell therapy, particularly Yescarta, also known as axi-cel, the initial studies investigating its role excluded patients with primary CNS lymphoma or any central nervous system involvement. Part of the reason was that these therapies were associated with significant neurotoxicity, even in patients who did not have brain tumors. Naturally, there was concern that toxicities might be even higher in patients with existing brain tumors.

When the FDA previously approved Yescarta for lymphomas, those studies had excluded patients with primary CNS lymphoma. However, in our study, we concluded that not only was it safe to use Yescarta in patients with CNS lymphoma, but it was just as safe as it was in patients with systemic lymphoma without CNS involvement. In addition, we found that the treatment works very well, with high efficacy in our patient population.

That was very encouraging to see in this hard-to-treat group of patients. The implications are significant because we are seeing both safety and evidence of efficacy for axi-cel in CNS lymphoma.

Transcript has been edited for clarity and conciseness.

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