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ASH 2020: Phase II ZUMA-12 Study Investigates First-Line Axicabtagene Ciloleucel for High-Risk Large B-Cell Lymphoma


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The phase II ZUMA-12 trial found that axicabtagene ciloleucel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, is a safe and effective first-line therapy for patients with high-risk large B-cell lymphoma. These results were presented by Sattva S. Neelapu, MD, and colleagues at the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 405).

Historically, around half of patients with high-risk large B-cell lymphoma—a subgroup of the disease in which patients have double- or triple-hit lymphoma or additional clinical risk factors identified by the International Prognostic Index—do not reach long-term disease remission with typical treatment approaches like chemoimmunotherapy.

Sattva S. Neelapu, MD

Sattva S. Neelapu, MD

“This trial is a step toward moving CAR T-cell therapy to first-line therapy for patients with aggressive B-cell lymphoma,” said principal investigator Dr. Neelapu, Professor of Lymphoma and Myeloma at The University of Texas MD Anderson Cancer Center. “Currently, patients with newly diagnosed aggressive B-cell lymphoma receive approximately 6 months of chemotherapy. If successful, CAR T-cell therapy could change it to a one-time infusion with therapy completed within 1 month.”

Interim Analysis of ZUMA-12

Axicabtagene ciloleucel is currently approved for treatment of adults with relapsed or refractory large B-cell lymphoma who already have received two or more lines of systemic therapies, based on the pivotal ZUMA-1 study. The phase II, open-label, single-arm, multicenter ZUMA-12 trial expands on the ZUMA-1 findings to evaluate the use of axicabtagene ciloleucel as first-line therapy for patients with high-risk large B-cell lymphoma.

The interim analysis of ZUMA-12 shows that 85% of patients treated with axicabtagene ciloleucel experienced overall response, and 74% experienced complete response. Seventy percent of the patients enrolled had an ongoing response at the data cutoff, after a median follow-up of 9.3 months.

The most common adverse events associated with axicabtagene ciloleucel included white blood cell count decrease, encephalopathy, anemia, and cytokine release syndrome. All adverse events were resolved by the time of data analysis.

Additionally, the peak level of CAR T cells present within the blood, as well as the median CAR T-cell expansion, was increased in this trial of first-line CAR T-cell therapy, compared to when the immunotherapy products were generated from patients who have already received several lines of chemotherapy.

“This T-cell fitness could be associated with improved effectiveness of treatment, leading to better outcomes for patients,” said Dr. Neelapu.

Following the interim results of ZUMA-12, the investigators plan to conduct continued follow-up to confirm durability of the patients’ responses to the treatment.

“If the responses are durable after longer follow-up, a randomized clinical trial would be needed to definitively demonstrate that CAR T-cell therapy is superior to existing standard of care with chemoimmunotherapy in these high-risk patients,” said Dr. Neelapu. “Furthermore, it raises the question of whether CAR T-cell therapy also should be evaluated in intermediate-risk patients with large B-cell lymphoma.”

Disclosure: This research was supported by Kite Pharma. For full disclosures of the study authors, visit ash.confex.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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