Gilead Releases 5-Year Follow-Up Data on Yescarta for Large B-Cell Lymphoma

CAR T-cell therapy shows durable long-term survival in patients with refractory LBCL, company’s Kite subsidiary says.

Gilead subsidiary Kite has announced positive 5-year follow-up data from the ZUMA-1 trial of axicabtagene ciloleucel, (Yescarta) for the treatment of refractory large B-cell lymphoma (LBCL).

Among all patients treated with Yescarta, the 5-year overall survival (OS) rate was 42.6% (95% CI, 32.8 – 51.9). Among patients who had a complete response (CR), the 5-year OS rate was 64.4% (95% CI, 50.8 – 75.1), and median survival time has yet to be reached. Among treated patients alive at 5 years, 92% have received no additional treatment since their 1-time infusion of Yescarta, suggestive of a cure for these patients.

The data were presented on December 11, 2021, at the 63rd American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract #1764).

“At 5 years, these data demonstrate impressive and durable survival benefit with axicabtagene ciloleucel in patients with refractory LBCL,” Caron Jacobson, MD, MMSc, medical director of the immune effector cell therapy program at the Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School, said in a statement.

“Nearly half of patients in the ZUMA-1 trial are still alive at 5 years, a group that previously had an average life expectancy of only 6 months. These results are a truly transformative shift in the standard of care for this disease,” Jacobson said.

Since the 4-year analysis, there had been 1 death in the study related to a secondary malignancy from prior chemotherapy and/or conditioning chemotherapy-related myelodysplastic syndrome while the individual was in complete remission from LBCL.

The presenters also reported an exploratory analysis of ZUMA-1 data showed a high degree of correlation between long-term OS and event-free survival (EFS) status, which could potentially support the use of 1- and 2-year EFS as surrogate endpoints for long-term OS in relapsed and refractory LBCL. There were no new safety signals reported, including no drug-related secondary malignancies.

“Five-year survival in any cancer patient is a significant milestone and the point in which we dare to consider the word ‘cure,’” Frank Neumann, MD, PhD, global head of clinical development at Kite, said in the statement. “We set out to develop a treatment with curative intent, and Yescarta has delivered on this promise by transforming the outlook for LBCL for some of the sickest patients who have exhausted other treatment options.”

The most common adverse reactions in patients with LCBL included cardiac arrhythmias, chills, constipation, cough, cytokine release syndrome (CRS),decreased appetite, diarrhea, dizziness, encephalopathy, fatigue, febrile neutropenia, fever, headache, hypotension, hypoxia, infections with pathogen unspecified, nausea, tachycardia, tremors, and vomiting.Axicabtagene ciloleucel is approved with a risk evaluation and mitigation strategy because of the risks of CRS and neurologic toxicities.

CRS, including fatal or life-threatening reactions, occurred in 88% of individuals with non-Hodgkin lymphoma (NHL), including Grade ≥3 in 10%. CRS occurred in 94% of individuals with LBCL, including Grade ≥3 in 13%.

Neurologic toxicities, including fatal or life-threatening reactions, occurred in in 81% (206/254) of all patients with NHL receiving Yescarta, including Grade ≥3 in 26%. Neurologic toxicities occurred in 87% (94/108) of patients with LBCL, including Grade ≥3 in 31%.

Axicabtagene ciloleucel was the first CAR T-cell therapy to be approved by the FDA for the treatment of adult individuals with relapsed or refractory LBCL after 2 or more lines of systemic therapy.

Reference

Yescarta is first CAR T-cell therapy to report five-year survival data from pivotal study showing durable long-term survival in patients with refractory large B-cell lymphoma. Gilead. News release. December 11, 2021. Accessed December 13, 2021. https://www.gilead.com/news-and-press/press-room/press-releases/2021/12/yescarta-is-first-car-t-cell-therapy-to-report-five-year-survival-data-from-pivotal-study-showing-durable-long-term-survival-in-patients-with-refract