06/03/2019 | Press release | Distributed by Public on 06/03/2019 07:37
Kite, a Gilead Company (NASDAQ:GILD), today announced findings from two new analyses from the ZUMA-1 trial of Yescarta® (axicabtagene ciloleucel) in adult patients with relapsed or refractory large B-cell lymphoma. These results include a two-year sub-population analysis of efficacy and safety in ZUMA-1 patients (registrational Cohorts 1 and 2) by age, as well as preliminary data from a separate safety management study of patients receiving early steroid intervention for cytokine release syndrome (CRS) and neurologic events. The results were presented today at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting May 31 - June 4, in Chicago.
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'Longer-term data from ZUMA-1 have shown more than half of patients were still alive two years after treatment with Yescarta,' said John McHutchison, AO, MD, Chief Scientific Officer and Head of Research and Development, Gilead Sciences. 'We are committed to further defining the clinical profile of Yescarta, including evaluation of new safety management protocols to further enhance patient care and help move the cell therapy field forward.'
Yescarta was the first CAR T cell therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of CRS and neurologic toxicities; see below for Important Safety Information.
Two-Year Analysis of ZUMA-1 by Age Supports Clinical Benefit of Yescarta in Patients 65 and Older (Abstract #7555)
Patients with relapsed large B-cell lymphoma in the two-year follow-up of ZUMA-1 were analyzed in two groups - those 65 years or older (≥65) (n=24) and those younger than 65 years (<65) (n=77). With a median follow-up of 27.1 months, the objective response rate (ORR) per investigator assessment was 92 percent among ≥65 patients and 81 percent in the <65 group, with 75 percent and 53 percent of patients in the respective groups achieving a complete response. At two years, 42 percent of ≥65 patients and 38 percent of <65 patients were in an ongoing response. The 24-month overall survival rate was 54 percent and 49 percent in each respective group. Among all patients in the safety analysis (27 patients ≥65 and 81 patients <65), most (98 percent) experienced Grade ≥3 adverse events. Grade ≥3 neurologic events occurred in 12 patients ≥65 (44 percent) and in 23 patients <65 (28 percent). Grade ≥3 CRS occurred in 2 patients ≥65 (7 percent) and in 10 patients <65 (12 percent).
'Patients with refractory large B-cell lymphoma who have exhausted treatment options and are still facing progressive disease are often older,' said Sattva S. Neelapu, MD, ZUMA-1 co-lead investigator and Professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center. 'Our results showed axicabtagene ciloleucel offered clinical benefit with a manageable safety profile in people aged 65 and over, which reinforces this therapy's use in these patients who otherwise have limited treatment options.'
Preliminary Results Expand Understanding of CAR T Safety Profile (Abstract #7558)
Kite is currently conducting various studies to further evaluate the efficacy and safety profile of Yescarta, including clinical trials evaluating use of bridging chemotherapy and other combination approaches.
In a ZUMA-1 safety management study (Cohort 4), patients with relapsed or refractory large B-cell lymphoma treated with Yescarta received earlier steroid intervention beginning when patients experienced Grade 1 neurologic events and at Grade 1 CRS when no improvement was observed after three days of supportive care.
As of the abstract data cut-off, 21 of 40 planned patients had received Yescarta, with a median follow-up of 7.7 months; 76 percent of patients received corticosteroids and 86 percent received tocilizumab. Grade ≥3 adverse events occurred in 95 percent of patients; Grade ≥3 events included decreased neutrophil count (33 percent) and anemia (24 percent). Grade 1 or 2 neurologic events and CRS occurred in 48 percent and 100 percent of patients, respectively. No patients experienced Grade ≥3 CRS, and Grade ≥3 neurologic events occurred in only 10 percent of patients, both numerically lower than in the registrational cohorts of ZUMA-1. There were no deaths due to adverse events in Cohort 4.
ORR per investigator assessment was 81 percent in the cohort, and 62 percent of patients achieved a complete response. The median duration of response has not yet been reached.
'Preliminary results of the ZUMA-1 expansion cohort suggest early steroid interventions may reduce the incidence of severe CRS and neurologic events associated with Yescarta without impacting the high response rates to Yescarta therapy in relapsed or refractory large B-cell lymphoma,' said Max S. Topp, MD, ZUMA-1 cohort 4 lead investigator and Professor and Head of Hematology, University Hospital of Wuerzburg, Germany. 'While longer follow-up in a greater number of patients is required, response rates thus far have been comparable to the pivotal ZUMA-1 study cohorts and rates of Grade 3 or higher CRS and neurologic events have been lower in this preliminary analysis, suggesting that early adverse event management with steroids may further improve the benefit/risk profile of CAR T therapy.'
U.S. Important Safety Information for Yescarta
BOXED WARNING:CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITIES