Axi-cel CAR-T effective in patients with transplant-ineligible large B-cell lymphoma
Key takeaways:
- Axicabtagene ciloleucel demonstrated superior efficacy as second-line therapy compared with standard of care in historical control patients.
- Researchers noted no unexpected treatment-related toxicities.
Second-line therapy with axicabtagene ciloleucel induced a complete metabolic response in 71% of adults with relapsed or refractory large B-cell lymphoma ineligible for autologous stem cell transplant, results of a phase 2 study showed.
Findings from the trial — published in Nature Medicine — suggested no new safety signals, with relatively low levels of cytokine release syndrome (CRS) and neurotoxicity.
“Transplant ineligible patients with aggressive relapsed or refractory B-cell lymphomas face poor prognosis,” Roch Houot, MD, head of the hematology department at University Hospital of Rennes, France, and coordinator of the ALYCANTE study, said in a Kite Pharma-issued press release. “ALYCANTE is the first study to assess axicabtagene ciloleucel as second-line therapy for transplant ineligible [relapsed/refractory large B-cell lymphoma], and the results showed high response rates and durable remission in this hard-to-treat population.”
Background and methodology
Axicabtagene ciloleucel (Yescarta, Kite Pharma/Gilead Sciences) — also known as axi-cel — is a CD19-directed chimeric antigen receptor T-cell therapy that has demonstrated superior efficacy as second-line treatment among individuals with high-risk relapsed or refractory large B-cell lymphoma who are eligible for autologous hematopoietic stem cell transplantation (HSCT), according to study investigators. FDA approved the agent last year as initial treatment of relapsed or refractory large B-cell lymphoma based on data from the ZUMA-7 trial.
However, about half of patients with relapsed or refractory large B-cell lymphoma are not suitable for autologous HSCT, so researchers conducted the open label phase 2 ALYCANTE trial to assess the safety and efficacy of axi-cel among patients with high-risk disease who are ineligible for high-dose chemotherapy and autologous HSCT.
The study enrolled 69 adults, 62 (mean age, 70.0 years; range, 49–81; 75.8% male;) of whom underwent preconditioning lymphodepletion followed a single infusion of axi-cel.
Investigator-assessed complete metabolic response evaluated 3 months after axi-cel infusion served as the study’s primary endpoint. Key secondary endpoints included PFS, OS and safety.
Results, next steps
The study met its primary endpoint, as researchers observed a complete metabolic response rate of 71% (95% CI, 58.1-81.8) 3 months after infusion, compared with 12% using standard-of-care treatment based on historical controls.
At 6-month follow-up, 59.7% (n = 37) of those treated continued to have a compete metabolic response to therapy.
At a median follow-up of 12 months (range, 2.1-17.9), researchers noted median PFS of 11.8 months (95% CI, 8.4 to not reached), with 48.8% (95% CI, 34-62) of patients evaluated being alive and progression free at 12 months.
Researchers reported a 12-month OS rate of 78.3% (95% CI, 64.7-87.1), with median OS duration that had not been reached.
Researchers also noted no unexpected treatment-related toxicities.
Grade 3 and 4 CRS occurred in 8.1% of patients and neurotoxicity in 14.5%.
The study results are limited by the small sample size, relatively short follow-up time and a single-arm design lacking a control group, according to the investigators.
With nearly half of patients with relapsed or refractory large B-cell lymphoma considered ineligible for autologous HSCT or high-dose chemotherapy due to various factors — such as advanced age, frailty and coexisting medical conditions — researchers said this study provides evidence of a new and effective treatment option moving forward.
References:
- Houot R, et al. Nat Med. 2023;doi:10.1038/s41591-023-02572-5.
- Kite’s CAR T-cell therapy Yescarta demonstrates high response rate and durable remission in ALYCANTE study as initial treatment for transplant ineligible patients with relapsed/refractory large B-cell lymphoma (press release). Available at: https://investors.gilead.com/news/news-details/2023/Kites-Car-T-cell-Therapy-Yescarta-Demonstrates-High-Response-Rate-and-Durable-Remission-in-ALYCANTE-Study-as-Initial-Treatment-for-Transplant-Ineligible-Patients-With-RelapsedRefractory-Large-B-cell-Lymphoma/default.aspx. Published Sept. 18, 2023. Accessed Sept. 18, 2023.
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