FDA approves Yescarta for advanced follicular lymphoma
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The FDA granted accelerated approval to axicabtagene ciloleucel for treatment of adults with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy, according to a press release from the agent’s manufacturer.
Axicabtagene ciloleucel (Yescarta; Kite Pharma, Gilead), also known as axi-cel, is an autologous chimeric antigen receptor T-cell therapy that targets the CD19 protein on the surface of cancer cells.
Axi-cel is the first CAR T-cell therapy approved for use in follicular lymphoma. The FDA approved the agent in October 2017 for treatment of adults with relapsed or refractory large B-cell lymphoma.
The FDA based the current approval on results of the single-arm, open-label, phase 2 ZUMA-5 trial. The most recent efficacy results of the trial showed 91% of patients with relapsed or refractory follicular lymphoma (n = 81) responded to one infusion of axi-cel. Nearly three-quarters (74%) of those patients remained in complete remission at 18 months of follow-up, according to researchers.
Median duration of response among all patients with follicular lymphoma had not been reached at median follow-up of 14.5 months.
“This is an important day for patients with high-risk and multiple-relapsed follicular lymphoma, which is a potentially fatal disease,” Caron A. Jacobson, MD, MMSc, ZUMA-5 trial lead investigator, medical director of the immune effector cell therapy program at Dana-Farber Cancer Institute and assistant professor of medicine at Harvard Medical School, told Healio.
Despite being an indolent disease for most patients, those with high-risk disease account for approximately a quarter of patients with follicular lymphoma, according to Jacobson. These patients, as well as those with multiple-relapsed disease, have short OS and need more effective treatment options, she added.
“Axi-cel is that better treatment option for a vast majority of these patients,” she said. “Although longer follow-up is needed of axi-cel in patients with follicular lymphoma, duration of response and PFS are already better than available options and it is possible that axi-cel may be a definitive — aka curative — therapy for a subset of these patients.”
Safety results of ZUMA-5 showed 8% of patients had grade 3 or higher cytokine release syndrome and 21% had grade 3 or higher neurotoxicity after a single infusion of axi-cel.
Jacobson said axi-cel had a better safety profile than observed among patients who received the therapy for diffuse large B-cell lymphoma. Additionally, the median time to onset of CRS among patients with follicular lymphoma was 4 days, “which means that axi-cel is not only potentially safer in [follicular lymphoma] than in DLBCL, but it has the potential for outpatient dosing,” Jacobson said.
Axi-cel will include a boxed warning that outlines risks for CRS and neurotoxicity associated with CAR T-cell therapy. The therapy is available only through the Yescarta Risk Evaluation and Mitigation Strategy program, part of the FDA’s posttreatment monitoring program.
“Available therapies in the third line for follicular lymphoma generally yield single-digit complete response rates and duration of response is on the order of about 1 year,” Jacobson told Healio. “Axi-cel leads to complete responses in an impressively high proportion of patients and median PFS has not been reached with median follow-up of 18 months. It, therefore, already surpasses available standard therapies.”
For more information:
Caron A. Jacobson, MD, MMSc, can be reached at caron_jacobson@dfci.harvard.edu.
Perspective
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Lee Greenberger, PhD
Axi-cel produced impressive response rates in the ZUMA-5 trial for patients with relapsed or refractory follicular lymphoma. Follicular lymphoma is the most common indolent non-Hodgkin lymphoma and can often be managed with existing therapies, but axi-cel is an important new treatment option for the 25% of patients who will go on to develop high-risk forms of the disease. Beyond that, axi-cel offers the possibility of controlling the disease with a single round of therapy compared with multiple rounds of chemoimmunotherapy.
Longer follow-up is needed to know the full benefits of axi-cel but, based on the PFS and duration of response reported in ZUMA-5, it gives new hope to patients with third-line relapsed or refractory follicular lymphoma.
Long-term follow-up data from the ZUMA-1 trial provide ample reason for optimism. Close to half of the 101 patients in ZUMA-1 with refractory large B-cell lymphoma are still alive 4 years after axi-cel infusion.
Years of experience with axi-cel also means that physicians have a clear picture of its short- and long-term safety, including the risk for CRS and immune effector cell-associated neurotoxicity syndrome. Although both can be serious, physicians have learned how to recognize and treat these adverse effects as they become more experienced with CAR T-cell therapy.
'The Leukemia & Lymphoma Society has been there since the beginning with CAR T-cell therapy and shares in the excitement of this approval, but there is much more work to be done. Not everyone responds to CAR-T. Our ongoing investments will help predict who will respond to this breakthrough therapy, understand why others fail to respond and fund the next generation of CAR T-cell therapy to further improve outcomes.
We are also focused on making CAR-T available for more types of cancer and making it less costly and quicker to administer through the development of “off-the-shelf” therapies using donor T cells.
Reference:
Jacobson C, et al. Abstract 1187. Presented at: ASH Annual Meeting and Exposition (virtual meeting); Dec. 5-8, 2020.
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Press Release, Healio Interview
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