FDA approves Yescarta as second-line therapy for large B-cell lymphoma
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The FDA approved axicabtagene ciloleucel as second-line treatment for adults with large B-cell lymphoma who are refractory to first-line chemoimmunotherapy or experienced disease relapse within 12 months of initial treatment.
Axicabtagene ciloleucel (Yescarta, Kite Pharma/Gilead Sciences) — also known as axi-cel — is an autologous, gene-edited, CD19-directed chimeric antigen receptor T-cell therapy.
The FDA previously approved the therapy for adults with relapsed or refractory large B-cell lymphoma or follicular lymphoma who received two or more lines of systemic therapy.
The label expansion applies to patients with diffuse large B-cell lymphoma not otherwise specified, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma and DLBCL arising from follicular lymphoma. The agent is not indicated for treatment of patients with primary central nervous system lymphoma.
The new approval — which the FDA based on data from the randomized phase 3 ZUMA-7 trial, presented at last year’s ASH Annual Meeting and Exposition — makes axi-cel the first commercially available CAR T-cell therapy for initial treatment of relapsed or refractory large B-cell lymphoma.
Earlier treatment with the therapy has been “a game changer,” according to Andre Goy, MD, chief of the division of lymphoma and chairman and chief physician officer of John Theurer Cancer Center at Hackensack University Medical Center.
“Expectations have now been raised that we can cure many more patients with relapsed non-Hodgkin lymphoma,” Goy, a member of the Healio | Cell Therapy Next Peer Perspective Board, told Healio.
Most patients with non-Hodgkin lymphoma who relapse early or do not respond to initial therapy have high-risk disease and expereince disease relapse within the first year after initial treatment, Goy said.
The likelihood of providing durable treatment benefit to patients with high-risk diseases using the current standard of care — autologous hematopoietic stem cell transplantation — is approximately 10%, highlighting the need for a more effective treatment option.
“Using axi-cel as earlier therapy makes a lot of sense, and the study data show that it more than doubled the complete response rate compared with standard therapy,” Goy said. “We know from previous ZUMA studies that this is a very durable and efficient therapy for the achievement of complete responses, with very few relapses after 6 months.”
‘Definitive’ results
The multicenter ZUMA-7 trial included 359 patients (age range, 22-81 years; 30% aged 65 years or older) with relapsed or refractory large B-cell lymphoma.
Researchers randomly assigned study participants to axi-cel or standard of care for second-line treatment. Standard therapy included platinum-based salvage combination chemotherapy, followed by high-dose therapy and autologous HSCT for those who responded to salvage chemotherapy.
At median follow-up of 24.9 months, efficacy results showed axi-cel significantly improved EFS compared with standard therapy (8.3 months vs. 2 months; HR = 0.39; 95% CI, 0.3-0.51). Axi-cel also appeared associated with a significantly higher overall response rate (83% vs. 50%; OR = 5.31; 95% CI, 3.1-8.9) and complete response rate (65% vs. 32%).
“Definitive clinical trial results such as these do not come along often and should drive a paradigm shift in how patients with relapsed or refractory [large B-cell lymphoma] are treated moving forward,” principal investigator Jason Westin, MD, director of lymphoma clinical research and associate professor in the department of lymphoma/myeloma at The University of Texas MD Anderson Cancer Center, said in a Kite Pharma-issued press release. “Patients who do not respond to or relapse after initial treatment should quickly be referred to a CAR T-cell therapy-authorized treatment center for evaluation.”
A new standard?
Prior to the FDA’s decision, the National Comprehensive Cancer Network updated its clinical practice guidelines to include axi-cel as a category 1 recommendation for patients with early relapsed or primary-refractory DLBCL.
“Axi-cel will become the standard of care,” Goy told Healio, adding that autologous HSCT likely will become obsolete for patients with relapsed or refractory large B-cell lymphoma.
“There are a number of benefits with CAR-T but, more importantly, the outcomes are way better,” Goy said. “The patient community wants CAR T cells because autologous transplant is much more complicated, and CAR-T is a one-time treatment.”
The decision to expand the axi-cel label to second-line treatment means that patients with high-risk disease no longer will need to endure multiple relapses to become eligible for the therapy, according to Stephen J. Forman, MD, director of Hematologic Malignancies Research Institute at City of Hope Comprehensive Cancer Center and a member of the Healio | Cell Therapy Next Peer Perspective Board.
“In addition, it means that a proportion of patients probably will never need to have an autologous transplant or any other chemotherapy,” he told Healio.
Forman agreed CAR-T likely will become standard for patients with high-risk DLBCL, including those with chemorefractory disease or those who relapse soon after first-line treatment.
Nevertheless, the future of HSCT for patients with relapsed or refractory disease remains unclear, and the study that led to the label expansion “leave[s] many questions unanswered,” Forman said.
“The cure rate with cellular therapy is still in the 35% to 40% range, and it is not yet clear who benefits most,” Forman said.
“[The ZUMA-7 study] does not answer the question of whether an autologous transplant performed in remission after CAR T-cell therapy will improve the overall cure rate,” he added. “In that sense, CAR T cells could be a bridge to transplant in the same way as second-line chemotherapy.”
References:
FDA approves axicabtagene ciloleucel for second-line treatment of large B-cell lymphoma (press release). www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-axicabtagene-ciloleucel-second-line-treatment-large-b-cell-lymphoma. Published April 1, 2022. Accessed April 3, 2022.
Locke FL, et al. Abstract 2. Presented at: ASH Annual Meeting and Exposition; Dec. 11-14, 2021; Atlanta.
NCCN clinical practice guidelines in oncology: B-cell lymphomas. Available at: www.nccn.org/guidelines/guidelines-detail?category=1&id=1480. Revised March 21, 2022. Accessed April 3, 2022.
Yescarta (prescribing information). Santa Monica, CA: Kite Pharma, Inc.; 2022.
Yescarta receives U.S. FDA approval as first CAR T-cell therapy for initial treatment of relapsed or refractory large B-cell lymphoma (press release). www.kitepharma.com/news/press-releases/2022/4/yescarta-receives-us-fda-approval-as-first-car-tcell-therapy-for-initial-treatment-of-relapsed-or-refractory-large-bcell-lymphoma-lbcl. Published April 1, 2022. Accessed April 3, 2022.
For more information:
Stephen J. Forman, MD, can be reached at sforman@coh.org.
Andre Goy, MD, can be reached at goy.andre@hackensackmeridian.org.
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