FDA Grants Accelerated Approval to Glofitamab-gxbm for Relapsed/Refractory DLBCL

On June 15, 2023, the U.S. Food and Drug Administration approved Glofitamab-gxbm (Columvi) for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma arising from follicular lymphoma. These patients needed to have exhausted two or more lines of systemic therapy. Glofitamab is a bispecific CD20-CD3 T cell engager.

 

Study ID number: NCT03075696

 

The approval was based on a multicenter, open-label, dose-escalation, and dose-expansion trial that included 132 patients with DLBCL who were relapsed or refractory to prior treatment. 20% of these patients had LBCL arising from follicular lymphoma. Patients with active CNS disease or previous involvement were excluded. The drug was administered through 13 intravenous infusions over a maximum of 12 cycles, including step-up dosing, until disease progression or intolerance. Following the first cycle, Glofitamab was given once every three weeks.

 

Efficacy was established based on the primary endpoint of overall response rate (ORR) and the secondary endpoint of complete response rate (CR).

 

The trial confirmed the specific patient population with relapsed or refractory DLBCL. It showed that Glofitamab-gxbm demonstrated an overall response rate (ORR) of 56% and a complete response (CR) rate of 43%. The median time to response was 42 days. Additionally, 68.5% of patients who achieved a response continued to respond for nine months or longer. The median duration of response was 18.4 months.

 

The most common adverse events reported in the trial were cytokine release syndrome (CRS), musculoskeletal pain, fatigue, and rash. Patients were treated with a single dose of Obinutuzumab (a humanized anti-CD20 monoclonal antibody) seven days prior to therapy along with steroid, antihistaminic, and antipyretic to reduce the risk of cytokine release syndrome. Due to this risk, it is advised for the patients to be hospitalized during step-up dosing initially and for subsequent doses if there has been CRS >Grade 2.

 

Glofitamab-gxbm (Columvi) has been approved for the treatment of relapsed or refractory DLBCL in adult patients who have undergone at least two lines of systemic therapy. Genentech, the developer of Glofitamab-gxbm, announced its availability in the United States in the coming weeks. The continued approval of Glofitamab-gxbm’s indication may be contingent upon the results of a confirmatory trial.