Introduction
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma, making up about 30% of cases. For many people, it can be treated successfully with modern frontline chemoimmunotherapy. But some patients don’t achieve lasting remission, and even after second-line treatments like salvage therapy and stem cell transplant, the disease may return. This relapse highlights a serious gap in treatment options for people with relapsed or refractory (r/r) DLBCL.1
In recent years, new types of therapies have brought hope to patients facing this challenge. These include CAR T-cell therapy, antibody–drug conjugates (ADCs), and a newer class called bispecific antibodies (BsAbs). BsAbs work by binding to two targets at the same time, for example, CD20 on B cells and CD3 on T cells, helping the immune system’s T cells directly attack lymphoma cells. 1
Columvi (glofitamab) is one such bispecific antibody. With its unique design, it has shown promising results in clinical trials for patients with r/r DLBCL who have already undergone multiple lines of treatment. In fact, trial data revealed encouraging response rates, leading to its approval in 2023 for certain patients with difficult-to-treat large B-cell lymphomas. 1
Drug Background
Glofitamab comes under the category of bispecific antibody.1 Monoclonal antibody therapies have been an important part of treating blood cancers, but on their own, they often show limited results. A newer approach, called bispecific antibodies, has started to change this picture. Unlike regular antibodies that target just one marker, bispecific antibodies are specially engineered to attach to two different targets.2
This design allows them to do something powerful: they can bring immune cells directly to cancer cells, helping the body’s own defenses attack the tumor. For example, some bispecific antibodies connect a tumor cell with a T cell (a type of immune cell), so the T cell can then destroy the cancer cell. What makes this even more effective is that it doesn’t depend on the usual recognition system that T cells need, which means more T cells can get involved in fighting the cancer.2
With over a hundred different bispecific formats already developed, and more being explored, this is a rapidly growing area in cancer treatment.2
Approved Indications
Glofitamab received its first approval on 25 March 2023 in Canada for adults with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL not otherwise specified, DLBCL that develops from follicular lymphoma, and primary mediastinal B-cell lymphoma. This approval applies to patients who have already received two or more lines of systemic therapy and are either not eligible for CAR T-cell therapy, cannot receive it, or have already been treated with it.3
Mechanism of Action
Glofitamab helps in treating B-cell non-Hodgkin lymphomas by guiding the body’s own immune system to target cancer cells. It works by attaching itself in two directions: on one side, it binds to CD20, a marker found on B-cells (including the cancerous ones), and on the other side, it connects to CD3, a marker found on T-cells (the immune cells that fight infections and cancers). 3
By holding these two cells together, glofitamab creates a bridge called an “immunological synapse.” This close contact activates the T-cells, makes them multiply, and enables them to directly attack and destroy the CD20-positive B-cells. 3
Research has shown that glofitamab not only boosts the activity of T-cells already present inside the tumor, but it can also draw in T-cells from the bloodstream to join the fight. In addition, treatment with glofitamab can trigger the temporary release of certain signaling proteins, called cytokines (such as interferon-γ, IL-6, IL-2, IL-8, IL-10, IL-15, and IL-17), which are part of the immune response.3
Administration Protocol
Glofitamab is given as an intravenous infusion in 21-day treatment cycles. Because there is a risk of a side effect called cytokine release syndrome (CRS), the medicine is introduced gradually through a step-up dosing schedule. Before treatment begins, every patient must receive a single intravenous dose of obinutuzumab, given seven days earlier. This pretreatment helps lower the number of certain immune cells, making CRS less likely.3
The first cycle of glofitamab starts on day 8 with a dose of 2.5 mg, followed by 10 mg on day 15. From the second cycle onward, the recommended dose is 30 mg on the first day of each cycle. Treatment may continue for up to twelve cycles, or until the disease progresses or the side effects become too difficult to manage. 3
To make the infusions safer, patients are kept well hydrated and given medicines beforehand, including something to reduce pain or fever and an anti-histamine. An intravenous steroid is also given before the first four infusions, and again in later cycles if the patient had CRS in the past. After the first infusion, patients are monitored for at least ten hours, with additional monitoring during later doses if needed. If CRS does occur, it is managed with a medicine called tocilizumab, sometimes combined with steroids. 3
Side Effects
Glofitamab, like many cancer treatments, can cause side effects that patients and caregivers should be aware of. Commonly, it may lead to swelling in the face, arms, hands, lower legs, or feet, along with feelings of dizziness, lightheadedness, headaches, or a sensation of constant movement, as if the room is spinning. Some people experience trembling or weakness in the muscles of the arms, legs, or feet, as well as muscle cramps, stiffness, or pain. Numbness, tingling, or burning sensations in the hands or feet can also occur.4
In addition to these, glofitamab may affect the heart and lungs, causing chest pain, irregular heartbeat, cough, or shortness of breath. Joint and bone discomfort is possible, including swollen joints, joint or bone pain, and tender or swollen lymph nodes. Rapid weight gain or swelling at the tumor site can also appear in some patients. 4
Less common side effects include unusual bleeding or bruising, black tarry stools, chest tightness, fever, chills, sore throat, and mouth issues such as ulcers, sores, or white patches. Patients may also notice changes in mood or thinking, including depression, anxiety, disorientation, nightmares, vivid dreams, hallucinations, or unusual agitation. Other possible effects are painful or difficult urination, pale skin, unusual tiredness or drowsiness, and back or side pain. 4
Safety Warings
Glofitamab can cause serious side effects. One of the most common is cytokine release syndrome (CRS), which happens when the immune system reacts strongly to the medicine. Symptoms can include fever, fast heartbeat, low blood pressure, chills, and trouble breathing. Most cases resolve within a couple of days, but some can be severe or even fatal. To reduce risk, the medicine is given in a step-up dosing schedule, often with hospital monitoring for the first doses.5
Glofitamab can also affect the nervous system, causing headaches, dizziness, confusion, or sleepiness. Severe effects are rare but possible, so patients should avoid driving or operating heavy machinery if these symptoms appear. The medicine can increase the risk of serious infections, including COVID-19 and sepsis, and should not be started if an infection is active. Doctors may give preventive antibiotics and monitor closely during treatment. 5
Finally, Glofitamab may harm a developing fetus. Women who are pregnant or could become pregnant should use effective contraception during treatment and for one month after the last dose. 5
Clinical Data
Glofitamab has shown strong results in both relapsed or refractory and newly diagnosed DLBCL. In the NP30179 trial for relapsed or refractory patients, 39% achieved a complete response, usually within 42 days, and the overall response rate was 52%. Responses were generally long-lasting, and patients whose disease had relapsed after previous treatment responded particularly well (70%) compared with those with refractory disease (34%). 3
Similar outcomes were seen in a phase I study in China, where 52% of patients had a complete response and 63% had an overall response, with most responses ongoing at 10 months. In combination with polatuzumab vedotin, glofitamab also showed promising results, with 51% of patients achieving a complete response and an overall response rate of 80% in those who had received prior therapies. 3
For patients with newly diagnosed DLBCL, glofitamab given with R-CHOP chemotherapy in the NP40126 trial led to 76% achieving a complete response and 94% achieving an overall response, demonstrating high efficacy as a first-line therapy.3
Conclusion:
Glofitamab (Columvi) represents a new treatment option for people with difficult-to-treat large B-cell lymphomas, including those whose disease has returned after multiple therapies. Patients and caregivers should work closely with their healthcare team to understand the potential benefits and risks, follow all monitoring and safety instructions, and report any concerning symptoms promptly.
Note:
The information provided is for education purpose only and is subjected to prescribing information of the drug and the guidance of your treating physician. Always consult your health care provider before making any medical decision for starting your treatment.
Disclaimer:
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References:
- Hsu YT, Wu SJ, Kao HW, et al. Glofitamab as a salvage treatment for B-cell lymphomas in the real world: A multicenter study in Taiwan. Cancer. 2024;130(11):1972-1981. doi:10.1002/cncr.35217
- Duell J, Lammers PE, Djuretic I, et al. Bispecific Antibodies in the Treatment of Hematologic Malignancies. Clin Pharmacol Ther. 2019;106(4):781-791. doi:10.1002/cpt.1396
- Shirley M. Glofitamab: First Approval. Drugs. 2023;83(10):935-941. doi:10.1007/s40265-023-01894-5
- Finsterer J. Glofitamab-Associated Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) Presenting as Serial Seizures and Responding Positively to Antiseizure Drugs and Anakinra: A Case Report. Cureus. 2024;16(5):e60833. Published 2024 May 22. doi:10.7759/cureus.60833
- COLUMVI PRESCRIPTION DRUG LABEL
