Utomilumab improves the efficacy of CAR-T cell therapy for advanced large B-cell lymphoma

May 2022 Clinical trials Nalinee Pathak
Science template, DNA molecules background. Vector illustration.

The results of the ZUMA-12 trial indicate that the addition of utomilumab (an investigational 4-1BB agonist monoclonal antibody) after infusion with axicabtagene ciloleucel (axi-cel) may lead to improved clinical outcomes in patients with advanced large B-cell lymphoma (LBCL). The early results of this phase 1 study were presented at Tandem Meetings | Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR.

Axi-cel is an autologous, gene-edited CAR-T cell therapy approved in the USA to treat patients with advanced LBCL who have received two or more lines of systemic therapy. Despite better outcomes with axi-cel, there is still a need to improve it further.

According to Ran Reshef, MD, associate professor of medicine and clinical lead of the CAR-T Cell Program at Columbia University Medical Center, “It has been hypothesised that dual stimulation may improve CAR T-cell expansion and persistence that would lead to improved clinical outcomes,” “Preclinical evidence supports the use of utomilumab as a T-cell costimulatory molecule capable of enhancing axi-cel expansion and function.”


The phase-1 dose-escalation ZUMA-11 study enrolled 12 patients (median age, 62 years; range 44-77; 58% male) with advanced LBCL. The primary aim of the study was to determine the efficacy, safety and pharmco-kinetics of axi-cel plus utomilumab. Towards this, the researchers assigned patients to one of four cohorts based on the escalating dosage of utomilumab (10 mg, 30mg, 100 mg or 200mg).


The combination of axi-cel plus utomilumab induced an objective response rate in 75% (n=9) patients, and 58% (n=7) patients achieved complete response. All the patients treated with the highest dose of utomilumab (100mg) responded to therapy, among which four achieved complete response. The majority of patients experienced grade 3 or higher adverse events such as decreased neutrophil count (67%), anaemia (42%) and hypotension (8%).


The combination of axi-cel with utomilumab showed promising efficacy with a manageable toxicity profile. These findings support the need for further studies in larger cohorts of advanced LBCL patients.