Profile
General Information
Columvi (glofitamab-gxbm) I is a bispecific CD20-directed CD3 T-cell engager.
Columvi is specifically indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy.
Dosing/Administration
Columvi is supplied as a solution for intravenous administration. Administer only as an intravenous infusion.
Pretreat with a single 1,000 mg dose of obinutuzumab intravenously 7 days before initiation of Columvi (Cycle 1 Day 1).
Following pretreatment with obinutuzumab, administer Columvi according to the step-up dosing schedule below with appropriate premedication, including dexamethasone, to reduce the incidence and severity of CRS.
Due to the risk of CRS, patients should be hospitalized during and for 24 hours after completion of infusion of step-up dose 1 (2.5 mg on Cycle 1 Day 8). Patients who experienced any grade CRS during step-up dose 1 should be hospitalized during and for 24 hours after completion of step-up dose 2 (10 mg on Cycle 1 Day 15). CRS with step-up dose 2 can occur in patients who did not experience CRS with step-up dose 1. For subsequent doses, patients who experienced Grade ≥ 2 CRS with their previous infusion should be hospitalized during and for 24 hours after the completion of the next Columvi infusion.
Cycle 1:
- Day 1: Obinutuzumab
- Day 8: Step-up dose 1: 2.5 mg for 4 hours. For patients who experience CRS with their previous dose of Columvi, the time of infusion may be extended up to 8 hours.
- Day 15: Step-up dose 2: 10 mg for 4 hours. For patients who experience CRS with their previous dose of Columvi, the time of infusion may be extended up to 8 hours.
Cycle 2:
- Day 1: 30 mg for 4 hours. For patients who experience CRS with their previous dose of Columvi, the time of infusion may be extended up to 8 hours.
Cycle 3 to 12:
- Day 1: 30 mg for 2 hours. If the patient experienced CRS with the previous dose, the duration of infusion should be maintained at 4 hours.
Mechanism of Action
Columvi (glofitamab-gxbm) is a bispecific antibody that binds to CD20 expressed on the surface of B cells, and to CD3 receptor expressed on the surface of T cells. Glofitamab-gxbm causes T-cell activation and proliferation, secretion of cytokines, and the lysis of CD20-expressing B cells. Glofitamab-gxbm showed anti-tumor activity in vivo in mouse models of DLBCL.
Side Effects
Adverse effects associated with the use of Columvi may include, but are not limited to, the following:
- cytokine release syndrome
- musculoskeletal pain
- rash
- fatigue
- Grade 3 to 4 laboratory abnormalities: lymphocyte count decreased, phosphate decreased, neutrophil count decreased, uric acid increased, and fibrinogen decreased
The Columvi drug label comes with the following Black Box Warning: Cytokine Release Syndrome (CRS), including serious or fatal reactions, can occur in patients receiving Columvi. Premedicate before each dose, and initiate treatment with the Columvi step-up dosing schedule to reduce the risk of CRS. Withhold Columvi until CRS resolves or permanently discontinue based on severity.
Clinical Trial Results
This FDA approved Columvi under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Accelerated approval was based on the Phase I/II NP30179 study. Columvi was given as a fixed course for 8.5 months in 132 patients with DLBCL who had relapsed or were refractory to prior therapies, including about one-third (30%) who had received prior CAR T-cell therapy. An additional 83% were refractory to their most recent therapy. Results showed patients treated with fixed-duration Columvi achieved durable remission, with 56% of patients achieving an overall response and 43% of patients achieving a complete response. Over two-thirds of those who responded continued to respond for at least nine months. The OR rate is the combination of CR rate (a disappearance of all signs and symptoms of cancer) and partial response rate (a decrease in the amount of cancer in the body). The median duration of response was 1.5 years.