Axi-cel CAR-T significantly improves EFS among older patients with non-Hodgkin lymphoma
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Second-line therapy with axicabtagene ciloleucel conferred a greater than eightfold increase in median EFS compared with standard-of-care treatment for older patients with diffuse large B-cell lymphoma, according to phase 3 study results.
Axicabtagene ciloleucel (Yescarta; Kite Pharma/Gilead Sciences) — a CD19-directed chimeric antigen receptor T-cell therapy — also more than doubled the complete response rate among patients aged 65 years or older, a subgroup analysis of the ZUMA-7 study presented at European Society for Blood and Marrow Transplantation-European Hematology Association 4th European CAR T-cell Meeting showed.
Background
A patient’s age often can be a determining factor in whether patients with relapsed or refractory disease receive hematopoietic stem cell transplantation or CAR-T, Tom van Meerten, MD, PhD, internist-hematologist at University Medical Center Groningen, said during a presentation.
The safety and efficacy of treatments for these patients is especially significant given that the median age of diagnosis for DLBCL is 66 years, he added.
“A [small percentage] of patients with relapsed or refractory large B-cell lymphoma ultimately receive definitive therapy with highdose chemoimmunotherapy and autologous stem cell transplantation due to low fitness, intolerability to treatment or lack of response to platinumbased salvage chemotherapy,” van Meerten said. “For these reasons, new treatment options are needed, particularly among elderly patients.”
Methodology
The multicenter ZUMA-7 study 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 axicabtagene ciloleucel, commonly called axi-cel, or standard of care for second-line therapy. Standard therapy consisted of platinum-based salvage combination chemotherapy, followed by high-dose therapy and autologous hematopoietic stem cell transplant for those who responded to salvage chemotherapy.
Van Meerten and colleagues’ subset analysis consisted of participants aged 65 years or older (median age, 69 years; range, 65-81; 61% male) who received axi-cel (n = 51) or standard therapy (n = 58). Patients assigned axi-cel more frequently had high-risk features — including elevated lactate dehydrogenase and triple-/double-hit lymphoma — than those assigned standard therapy.
Most patients (96%) randomly assigned to axi-cel received their CAR-T infusion, whereas 34% of patients assigned standard therapy proceeded to HSCT.
Median follow-up was 24.3 months.
Key findings
The analysis met is primary endpoint, with efficacy results showing axi-cel significantly improved median EFS for older patients compared with standard therapy (21.5 months vs. 2.5 months; HR = 0.27; P < .0001) in the second-line setting. Multivariate analysis confirmed a similar EFS benefit for axi-cel (HR = 0.23; P < .0001) when adjusting for differences in baseline characteristics between groups.
Van Meerten and colleagues reported a significantly higher objective response rate (88% vs. 52%; OR = 8.81; 95% CI, 2.71-32.14) and complete response rate (75% vs. 33%) in the axi-cel group.
A higher proportion of patients in the axi-cel group experienced grade 3 or higher treatment-related adverse events. Researchers reported one treatment-related death in the standard therapy group and none in the axi-cel group.
Eight percent of patients in the axi-cel group experienced grade 3 or higher cytokine release syndrome. Neurologic toxicity occurred more frequently in the axi-cel group than standard therapy group (all grade, 65% vs. 25%; grade 3, 27% vs. 2%).
Clinical implications
Results from this subset analysis showed that axi-cel demonstrated superior efficacy as second-line therapy for older patients with diffuse large B-cell lymphoma, van Meerten said. The results are particularly impressive given that more patients in the axi-cel group had high-risk disease characteristics, he added.
In addition to superior outcomes, van Meerten highlighted that far more patients received their definitive therapy in the axi-cel group compared with the standard-of-care regimen that included HSCT.
“Axi-cel is an effective and manageable second-line therapy for elderly patients with relapsed or refractory large B-cell lymphoma,” he said. “[It] had a manageable safety profile consistent with previous studies and real-world experience, regardless of age.”
Collapse
van Meerten T, et al. Abstract PT02-1. Presented at: European Society for Blood and Marrow Transplantation-European Hematology Association 4th European CAR T-cell Meeting (virtual meeting); Feb. 10-12, 2022.
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