5-Year Follow-Up Supports Curative Potential of Axicabtagene Ciloleucel in Refractory Large B-Cell Lymphoma (ZUMA-1).
Sattva S NeelapuCaron A JacobsonArmin GhobadiDavid Bernard MiklosLazaros J LekakisOlalekan O OluwoleYi LinIra BraunschweigBrian T HillJohn M TimmermanAbhinav DeolPatrick M ReaganPatrick Joseph StiffIan W FlinnUmar FarooqAndre H GoyPeter McSweeneyJavier L MuñozTanya SiddiqiJulio C ChavezAlex F HerreraNancy L BartlettAdrian A BotRhine R ShenJinghui DongKanwarjit SinghHarry MiaoJenny J KimYan ZhengFrederick L LockePublished in: Blood (2023)
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 aimed to assess survival and safety in ZUMA-1 after 5 years of follow-up. Eligible adults with refractory LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, and transformed follicular lymphoma) received lymphodepleting chemotherapy followed by axi-cel infusion targeted at 2×106 cells/kg. Investigator-assessed response, updated survival, safety, and pharmacokinetic outcomes were assessed in treated patients. The objective response rate in the 101 treated patients was 83% (58% complete response rate), and with a median follow-up of 63.1 months, responses were ongoing at data cutoff in 31%. 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%. 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. ClinicalTrials.gov, number NCT02348216.
Keyphrases
- diffuse large b cell lymphoma
- cell therapy
- end stage renal disease
- newly diagnosed
- prognostic factors
- ejection fraction
- peripheral blood
- epstein barr virus
- free survival
- peritoneal dialysis
- stem cells
- lymph node
- clinical trial
- cell death
- metabolic syndrome
- rectal cancer
- bone marrow
- cancer therapy
- machine learning
- drug delivery
- risk assessment
- big data
- patient reported
- study protocol
- cross sectional
- platelet rich plasma
- ultrasound guided