Details

Autor(en) / Beteiligte

• Neelapu, Sattva S.
• Jacobson, Caron A.
• Ghobadi, Armin
• Miklos, David B.
• Lekakis, Lazaros J.
• Oluwole, Olalekan O.
• Lin, Yi
• Braunschweig, Ira
• Hill, Brian T.
• Timmerman, John M.
• Deol, Abhinav
• Reagan, Patrick M.
• Stiff, Patrick
• Flinn, Ian W.
• Farooq, Umar
• Goy, Andre H.
• McSweeney, Peter A.
• Munoz, Javier
• Siddiqi, Tanya
• Chavez, Julio C.
• Herrera, Alex F.
• Bartlett, Nancy L.
• Bot, Adrian A.
• Shen, Rhine R.
• Dong, Jinghui
• Singh, Kanwarjit
• Miao, Harry
• Kim, Jenny J.
• Zheng, Yan
• Locke, Frederick L.

Titel

Five-year follow-up of ZUMA-1 supports the curative potential of axicabtagene ciloleucel in refractory large B-cell lymphoma

Ist Teil von

• Blood, 2023-05, Vol.141 (19), p.2307-2315

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2023

Quelle

MEDLINE

Beschreibungen/Notizen

• •Axicabtagene ciloleucel induced long-term survival with no new safety signals in patients with refractory LBCL.•Durable responses were associated with expansion of chimeric antigen receptor T cells early after intravenous infusion. [Display omitted] In phase 2 of ZUMA-1, a single-arm, multicenter, registrational trial, axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy demonstrated durable responses at 2 years in patients with refractory large B-cell lymphoma (LBCL). Here, we assessed outcomes in ZUMA-1 after 5 years of follow-up. Eligible adults received lymphodepleting chemotherapy followed by axi-cel (2 × 106 cells per kg). Investigator-assessed response, survival, safety, and pharmacokinetics were assessed in patients who had received treatment. The objective response rate in these 101 patients was 83% (58% complete response rate); with a median follow-up of 63.1 months, responses were ongoing in 31% of patients at data cutoff. Median overall survival (OS) was 25.8 months, and the estimated 5-year OS rate was 42.6%. Disease-specific survival (excluding deaths unrelated to disease progression) estimated at 5 years was 51.0%. No new serious adverse events or deaths related to axi-cel were observed after additional follow-up. Peripheral blood B cells were detectable in all evaluable patients at 3 years with polyclonal B-cell recovery in 91% of patients. Ongoing responses at 60 months were associated with early CAR T-cell expansion. In conclusion, this 5-year follow-up analysis of ZUMA-1 demonstrates sustained overall and disease-specific survival, with no new safety signals in patients with refractory LBCL. Protracted B-cell aplasia was not required for durable responses. These findings support the curative potential of axi-cel in a subset of patients with aggressive B-cell lymphomas. This trial was registered at ClinicalTrials.gov, as #NCT02348216. Neelapu et al report on a 5-year follow-up of the ZUMA-1 trial of axicabtagene ciloleucel (axi-cel) autologous anti-CD19 chimeric antigen receptor T-cell therapy for refractory large B-cell lymphoma (LBCL) and confirm sustained response in those achieving complete response. At 5 years, 31% of treated patients had sustained responses, with an overall 5-year survival of 42.6%, increasing the probability that axi-cel has curative potential for a subset of patients with refractory aggressive LBCL.