A dual-antigen targeting combination of the CD19-targeting chimeric antigen receptor (CAR) T-cell therapy axicabtagene ciloleucel plus the CD20-targeting agent rituximab led to durable responses and reduced relapses in patients with refractory large B-cell lymphoma (LBCL), according to findings from the phase II ZUMA-14 trial published in Nature Cancer.
“Our study demonstrated the therapeutic benefit of targeting two antigens when treating [LBCL],” said lead study investigator Paolo Strati, MD, Associate Professor of Lymphoma at The University of Texas MD Anderson Cancer Center. “The combination of axicabtagene ciloleucel and rituximab produced deep and durable responses without introducing new safety concerns.”
Background and Study Methods
Although CD19-directed CAR T-cell therapies have been effective in patients with lymphoma, approximately 30% of patients will relapse after CAR T-cell therapy when the cancer cells stop expressing CD19.
The single-arm phase II ZUMA-14 trial enrolled 26 adult patients with chemorefractory LBCL who received the combination of axicabtagene ciloleucel and rituximab.
Key Findings
The complete response rate, the primary endpoint of the study, was 73%. The median duration of response was 26 months and 46% of patients had an ongoing response at data cutoff.
Peak CAR T-cell levels as well as rituximab area-under-the-curve levels were both elevated in patients who achieved a complete or ongoing response to the combination regimen.
No new safety signals were reported with the combination. Persistent B-cell aplasia and pharmacokinetics of axicabtagene ciloleucel were unaffected by the addition of rituximab, showing that the combination was safe and feasible as a method for blocking antigen escape and relapse.
DISCLOSURE: The study was funded by Kite. For full disclosures of the study authors, visit nature.com.
