The U.S. Food and Drug Administration ( FDA ) has granted accelerated approval to Yescarta ( Axicabtagene ciloleucel ) for the treatment of adult patients with relapsed or refractory follicular lymphoma ( FL ) after two or more lines of systemic therapy.
The approval makes Yescarta the first chimeric antigen receptor ( CAR ) T-cell therapy approved for patients with indolent follicular lymphoma.
The approval is based on results from ZUMA-5, a single-arm, open-label study in which 91% of patients with relapsed or refractory follicular lymphoma ( n=81 ) responded to Yescarta, including an estimated 74% of patients in a continued remission at 18 months ( Kaplan-Meier estimate ).
Among all patients with follicular lymphoma, median duration of response was not reached at a median follow-up of 14.5 months.
In the safety analysis set ( n=146 ), grade 3 or higher cytokine release syndrome ( CRS ) and neurologic toxicities occurred in 8% and 21% of patients, respectively.
For follicular patients in the third line of therapy, the five-year survival rate is only 20%, highlighting the urgent need for treatments that offer a real chance for durable remission.
91% of follicular lymphoma patients in the ZUMA-5 study responded to a single infusion of Axicabtagene ciloleucel, including an estimated 74% of patients in a continued remission at 18 months.
The Yescarta U.S. Prescribing Information has a BOXED WARNING for the risks of cytokine release syndrome and neurologic toxicities, and Yescarta is approved with a risk evaluation and mitigation strategy ( REMS ) due to these risks.
ZUMA-5 is an ongoing, single-arm, open-label, multicenter trial evaluating 146 patients ( 18 years old or more ) with relapsed or refractory iNHL, who received at least two prior lines of systemic therapy, including the combination of an anti-CD20 monoclonal antibody and an alkylating agent.
Efficacy was established on the basis of objective response rate ( ORR ) and duration of response ( DoR ) as assessed by an independent review committee per the 2014 Lugano Classification.
In the study, 91% of all patients with follicular lymphoma ( n=81 evaluable for efficacy analysis ) responded to a single infusion of Yescarta, including 60% of patients who achieved a complete remission.
Thirteen of the 25 patients who achieved a partial remission met imaging criteria for a complete remission without confirmation by negative bone marrow biopsy after treatment.
Median duration of response has not yet been reached.
Among the 146 patients evaluable for safety, grade 3 or higher cytokine release syndrome and neurologic toxicities were observed in 8% and 21% of patients, respectively.
The median time to onset of cytokine release syndrome and neurologic toxicities were four days ( range: 1 to 20 days ) and six days ( range 1 to 79 days ), respectively.
The most common ( 10% or more ) grade 3 or higher adverse reactions included febrile neutropenia, encephalopathy, and infections with pathogen unspecified.
Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:
a) 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;
b) adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Follicular lymphoma is a form of indolent non-Hodgkin lymphoma ( iNHL ) in which malignant tumors slowly grow but can become more aggressive over time.
Follicular lymphoma is the most common form of indolent lymphoma and the second most common type of lymphoma globally. It accounts for approximately 22% of all lymphomas diagnosed worldwide. ( Xagena )
Source: Gilead, 2021