glofitamab — Drug Monograph

Glofitamab (Columvi) — CD20xCD3 Bispecific for DLBCL

Glofitamab (Columvi) is a CD20xCD3 bispecific antibody for relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Its novel 2:1 format provides two CD20-binding arms and one CD3-binding arm, improving tumor-cell avidity as it engages CD20 on lymphoma cells and CD3 on T cells to drive T-cell-mediated killing. It is given as a fixed 12-cycle course (not indefinite) and requires obinutuzumab pretreatment to deplete circulating B cells and lower CRS risk. This monograph covers glofitamab indications in relapsed/refractory DLBCL, fixed-duration treatment, CD20/CD3 dual targeting, the step-up dosing schedule, mandatory obinutuzumab premedication, and CRS monitoring.

Indications (FDA / NCCN)

• Relapsed or refractory DLBCL NOS or LBCL arising from follicular lymphoma, after ≥2 prior lines including anti-CD20 therapy (NP30179)
• FDA accelerated approval (June 2023)
• Fixed 12-cycle course — treatment stops after Cycle 12

Dosing

• Obinutuzumab 1000 mg IV on C1D1, 7 days before the first glofitamab step-up dose
• IV step-up: 2.5 mg (C1D8) → 10 mg (C1D15) → 30 mg (C2D1 and each cycle through C12)
• 21-day cycles; first infusion over ≥4 h, may shorten if tolerated
• Hospitalize for the 2.5 mg step-up dose (and subsequent as recommended)

Monitoring

• CRS signs/symptoms for ≥24 h after each step-up dose (~63% any grade)
• ICANS / neurologic toxicity
• Tumor lysis syndrome risk with obinutuzumab pretreatment
• CBC and for infections

Brand names: Columvi

Drug class: Other

Mechanism of Action

CD20×CD3 bispecific monoclonal antibody with a novel 2:1 bivalent format (two CD20-binding Fab arms and one CD3-binding Fab arm), enabling bivalent engagement of CD20 on B-cell lymphoma cells and monovalent engagement of CD3ε on T cells. This configuration leads to T-cell activation and cytotoxic killing of CD20-positive tumor cells. The 2:1 format improves tumor cell avidity compared to 1:1 bispecifics.

FDA Indications

• Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after ≥2 prior lines of systemic therapy, including anti-CD20 therapy (FDA accelerated approval June 2023, based on NP30179: 39% complete response rate)

Common Side Effects

• CRS (63%)
• Pyrexia
• Fatigue
• Musculoskeletal pain
• Rash
• Neutropenia
• Anemia
• Thrombocytopenia
• Infections

Clinical Pearl

Glofitamab is the first CD20×CD3 bispecific antibody with a fixed-duration treatment course (12 cycles), a meaningful distinction from indefinite checkpoint inhibitor therapy. The obinutuzumab pretreatment step (1000 mg IV, 7 days prior to the first glofitamab dose) is mandatory — not optional — and substantially reduces CRS incidence by depleting circulating CD20+ B cells before the bispecific is introduced.

Related Therapies & Mechanisms

• Axicabtagene ciloleucel (Yescarta) — Other · Lymphoma
• Belinostat (Beleodaq) — Other · Lymphoma
• Bleomycin (Blenoxane) — Other · Lymphoma
• Brexucabtagene autoleucel (Tecartus) — Other · Lymphoma