An analysis recently published in the American Journal of Hematology outlined the results of 2 phase 1 studies that examined urelumab for the treatment of relapsed or refractory (R/R) B-cell lymphoma. Ultimately, their analysis found that the combination of urelumab with rituximab did not provide a gain in clinical activity over rituximab monotherapy or the standard of care.

For this analysis, the researchers examined outcomes with urelumab, a fully human, monoclonal, immunoglobulin-gamma-4 antibody with CD137 agonist activity, in the CA186-011 and CA186-017 clinical trials. The CA186-011 trial (ClinicalTrials.gov Identifier: NCT01471210) evaluated urelumab monotherapy, and results from patients with R/R B-cell non-Hodgkin lymphoma (NHL; 60 patients) were analyzed in this report. The CA186-017 trial (ClinicalTrials.gov Identifier: NCT01775631) assessed urelumab with rituximab in treatment of R/R B-cell NHL (46 patients).

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The maximum tolerated dose of urelumab was 0.1 mg/kg or 8 mg every 3 weeks. Among patients receiving urelumab monotherapy, 52% experienced treatment-related adverse events, with grade 3 to 4 treatment-related adverse events reported in 15% of patients. Among patients receiving urelumab with rituximab, 72% reported treatment-related adverse events, with grade 3 to 4 treatment-related adverse events in 28% of patients and 1 death from sepsis syndrome.

Objective response rates (ORRs) for patients given urelumab monotherapy were 6% for patients with diffuse large B-cell lymphoma (DLBCL), 12% for those with follicular lymphoma (FL), and 17% for those with other B-cell NHLs. However, the researchers noted, 50% of responses with urelumab monotherapy were at a dosage above the maximum tolerated dose. The combination of urelumab with rituximab gave ORRs of 10% in patients with DLBCL and 35% in patients with FL.

For patients with DLBCL or FL, the median duration of response was not reached with either urelumab monotherapy or the combination therapy. In patients with other B-cell NHLs, the median duration of response was 18.1 weeks for urelumab monotherapy.

“In the CA186-011 and CA186-017 studies, antitumor activity, including several durable remissions, was observed with urelumab as monotherapy or in combination with rituximab; however, many of these responses were observed at doses that exceeded the [maximum tolerated dose],” the researchers wrote.

Reference

1.     Timmerman J, Herbaux C, Ribrag V, et al. Urelumab alone or in combination with rituximab in patients with relapsed or refractory B-cell lymphoma [published online February 13, 2020]. Am J Hematol. doi:10.1002/ajh.25757