Dr Carlo-Stella on the FDA Approval of Glofitamab in Relapsed/Refractory DLBCL

Carmelo Carlo-Stella, MD, PhD, Department of Biomedical Sciences, Humanitas University, Department of Oncology and Hematology, IRCCS Humanitas Research Hospital, discusses the FDA approval of glofitamab-gxbm (Columvi) for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma arising from follicular lymphoma, after at least 2 lines of systemic therapy.

The June 15, 2023, approval was based on findings from the phase 1/2 NP30179 trial (NCT03075696), which demonstrated that the CD20xCD3 T-cell–engaging bispecific antibody glofitamab led to a 56% overall response rate (ORR) and a complete response (CR) rate of 43%. Additionally, the median duration of response was 18.4 months (95% CI, 11.4-not estimable) and 68.5% of responders continued to respond for 9 months or longer (95% CI, 56.7-80.3).

In the study, the agent was administered in 13 intravenous infusions for up to 12 cycles, including step-up dosing, until disease progression or intolerance. Following cycle 1 of treatment, glofitamab was given once every 3 weeks. In terms of safety, the most common adverse effects (AEs; n = 145) were cytokine release syndrome (CRS; 70%), musculoskeletal pain (21%), fatigue (20%), and rash (20%). CRS was mostly low grade, occurring most often at grade 1 (52%) and grade 2 (14%).

The standard of care for patients with relapsed/refractory DLBCL has been cytotoxic chemotherapy, which fails to elicit responses in most patients, Carlo-Stella adds. As such, the approval is a great accomplishment, ridding some patients of large bulky tumors with lymph node involvement in a mere 2 days, Carlo-Stella says. The approval also sets the stage for further development of immunotherapy in this population, Carlo-Stella adds.

Continued approval for the current indication may be contingent upon the results of a confirmatory trial.