Author: By Shreeya Nanda, Senior medwireNews Reporter
medwireNews: Axicabtagene ciloleucel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, continues to show durable responses and a manageable safety profile with longer follow-up in patients with refractory large B-cell lymphoma, report the ZUMA-1 investigators.
They explain that the primary analysis at a median follow-up of 15.4 months showed an objective response rate (ORR) of 82% among the 108 participants of the phase I/II study after a single infusion of axicabtagene ciloleucel at a target dose of 2×106 CAR T cells/kg.
The current analysis – published in The Lancet Oncology and presented at the 60th American Society of Hematology Annual Meeting in San Diego, California, USA – was conducted when participants had been followed up for a median 27.1 months and showed that 83% of the 101 evaluable participants had an objective response that lasted for a median of 11.1 months.
Fifty-eight percent of the responses were complete, and for these patients the median duration of response was unreached, and 39% of patients had ongoing responses at data cutoff, note Frederick Locke, from the Moffitt Cancer Center in Tampa, Florida, USA, and co-investigators.
The median progression-free survival duration was 5.9 months, whereas the median was not reached for overall survival (OS) and the estimated 24-month OS rate was 50.5%.
The authors say that that these findings signify “a major improvement in clinical outcomes for these patients, for whom the expected median overall survival with conventional therapies is approximately 6 months, with a 2-year overall survival of approximately 20%.”
They add that the safety profile with longer follow-up was “manageable” and “largely similar to that in previous reports.”
The incidence of grade 3–5 cytokine release syndrome, infections and neurological events over the course of the study was 11%, 28% and 32%, respectively. No new cases of either cytokine release syndrome or neurological adverse events related to the CAR T-cell therapy occurred since the previous analysis, say the researchers.
However, four patients experienced adverse events of grade 3 or 4 since then, but none were considered related to treatment.
Frederick Locke et al conclude that “[a]xicabtagene ciloleucel can offer durable remissions to patients who otherwise lack treatment options.”
But they add that “[a]dditional studies are needed to confirm the overall survival results noted here and to establish whether axicabtagene ciloleucel can improve quality of life in this setting.”
The ZUMA-1 trial enrolled patients with large B-cell lymphoma – including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma and transformed follicular lymphoma – that had not responded to the most recent chemotherapy regimen or had progressed within a year of autologous stem cell transplantation. All participants had previously received a regimen containing an anti-CD20 agent as well as an anthracycline-based chemotherapy regimen.
Locke FL, Ghobadi A, Jacobson CA,
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