Glofitamab Gains Accelerated Approval for Relapsed/Refractory DLBCL

Glofitamab Gains Accelerated Approval for Relapsed/Refractory DLBCL

The FDA has approved glofitamab-gxbm (Columvi) as a fixed duration treatment for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after 2 or more lines of systemic therapy. Continued approval is contingent upon the findings of a confirmatory trial.¹

Data from the phase 1/2 NP30179 study (NCT03075696) support the regulatory decision.

Findings from the study revealed a 56% overall response rate (95% CI, 47%-65%) among patients with relapsed or refractory disease (n = 132), including a 43% (95% CI, 35%-52%) complete response rate, and an 18.4-month median duration of response (95% CI, 11.4-not estimable). Thirty percent of participants had received prior CAR T-cell therapy and 83% were refractory to their most recent therapy.¹

Regarding safety, the most common adverse events in the study included cytokine release syndrome (CRS; 70%), musculoskeletal pain (21%), fatigue (20%) and rash (20%). Fifty-two percent of CRS events were grade 1, and 14% were grade 2.¹

“Patients with relapsed or refractory DLBCL may experience rapid progression of their cancer and often urgently need an effective treatment option that can be administered without delay,” Krish Patel, MD, director of the Lymphoma Program at the Swedish Cancer Institute in Seattle and investigator of the phase I/II NP30179 study, stated in a news release.1 “Experience from clinical trials demonstrates that [glofitamab] can provide patients with relapsed or refractory DLBCL a chance for complete remission with a fixed-duration immunotherapy and that such remissions can potentially be sustained after the end of their treatment.”¹

In the United States, DLBCL is the most common form on non-Hodgkin lymphoma, and although many patients with this aggressive disease respond to treatments, patients who relapse or are refractory to prior treatment face poor prognoses.¹

Glofitimab is a fixed-duration bispecific antibody that is designed to latch on to both CD3 on the surface of the T cell and CD20 on the surface of B cells—which harbor the cancerous DLBCL cells.¹

The treatment is administered as 13 intravenous (IV) infusions. Patients receive this treatment for a maximum of 12 cycles (including the step-up dosing), or until they experience disease progression, or the treatment can no longer be tolerated. The treatment is intended to be completed in 8.5 months and following cycle 1, is administered once every 3 weeks.¹

The manufacturers note that the target end date for the treatment course, and the possibility of a treatment-free period may be appealing to some patients. Moreover, the chemotherapy-free treatment is off-the-shelf and ready for infusion, according to the news release.¹

Seven days prior to receiving glofitamab, patients will receive a single dose of obinutuzumab (Gazyva; 1000 mg). Patients should also receive premedication with corticosteroid, an antipyretic (fever-reducing medicine) and an antihistamine.^1,2

Lastly, to mitigate the risk of CRS, patients will receive this treatment with a step-up dose. For the first step-up dose, on day 8 (2.5 mg) of cycle 1, patients will be hospitalized for their infusion, and admitted for 24 hours following their infusion.^1,2 If patients experience CRS during the first step-up dose, they should again be admitted for the second step-up dose, on day 15 (10 mg). For subsequent infusions, patients should be admitted if they develop grade 2 or worse CRS with their previous dose.

Patients will receive their first full dose of treatment (30 mg) a week after their second step-up dose, on day 1 of cycle 2.^1,2

Moreover, throughout the course of treatment, patients will need to carry a glofitamab wallet card, which will list the signs and symptoms of CRS that indicate a need for emergency medical help.¹

The prescribing information lists warning for neurologic toxicities, serious infection, tumor flares, and embryo-fetal toxcitiy.² The most common laboratory abnormalities associated with this treatment are decreased lymphocyte count, decreased phosphate, decreased neutrophil count, increased uric acid increased, and decreased fibrinogen.

“People with DLBCL who have gone through multiple lines of therapy have a poor prognosis and desperately need additional treatment options,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development, added, in a news release.¹ “As an off-the-shelf, fixed-duration treatment providing durable response rates, we believe [glofitamab] could change the way this aggressive lymphoma is treated, reinforcing our dedication to bringing innovative treatment options to people with critical unmet needs.”¹

References

1. FDA approves Genentech’s Columvi, the first and only bispecific antibody with a fixed-duration treatment for people with relapsed or refractory diffuse large B-cell lymphoma. Genentech. June 15, 2023. Accessed June 16, 2023. https://www.gene.com/media/press-releases/14994/2023-06-15/fda-approves-genentechs-columvi-the-firs
2. Columvi. Prescribing information. Genentech, Inc; 2023. Accessed June 16, 2023. https://www.gene.com/download/pdf/columvi_prescribing.pdf