For individuals with multiple myeloma, the landscape of treatment is advancing, offering new options when initial therapies are no longer effective. Among these are teclistamab (Tecvayli) and talquetamab (Talvey). These are not traditional chemotherapies but immunotherapies designed for patients whose cancer has returned or has become resistant to other treatments. Both medications belong to a class of drugs known as bispecific antibodies, which leverage the body’s own immune system to fight cancer.
How Bispecific Antibodies Work Against Myeloma
Bispecific antibodies function as an immunological matchmaker, creating a bridge between the body’s cancer-fighting immune cells and myeloma cells. These engineered proteins have two distinct arms. One arm grabs onto a protein called CD3, found on the surface of T-cells, while the other arm latches onto a different protein found on myeloma cells.
By binding to both cell types, the antibody pulls a T-cell and a myeloma cell together. This forced proximity activates the T-cell, giving it a direct command to attack. The activated T-cell then releases chemical substances, such as perforins and granzymes, that puncture the myeloma cell’s membrane and trigger its destruction.
This mechanism turns the patient’s own immune system into a guided weapon. Unlike therapies requiring the complex process of modifying a patient’s T-cells, these are “off-the-shelf” drugs created in a laboratory. They are ready to be administered to engage the T-cells already circulating in the body, directing them to eliminate myeloma cells.
Targeting Myeloma Cells: BCMA vs. GPRC5D
The primary difference between teclistamab and talquetamab is the specific “handle” they use to identify myeloma cells. While both drugs engage T-cells using the CD3 protein, their other arm targets a distinct antigen on the cancer cell surface.
Teclistamab targets a protein known as B-cell maturation antigen (BCMA). BCMA is found in high amounts on the surface of malignant plasma cells, making it a well-established marker for multiple myeloma therapies. Its presence provides a reliable point of attachment for the drug.
In contrast, talquetamab targets a different protein called G-protein coupled receptor class 5 member D (GPRC5D). Like BCMA, GPRC5D is highly expressed on myeloma cells, offering an alternative docking point. This is useful if cancer cells have learned to reduce the amount of BCMA on their surface, a potential mechanism of resistance to other treatments.
The Treatment and Administration Process
Both teclistamab and talquetamab are administered through subcutaneous injection into the tissue just under the skin, usually in the abdomen. The treatment for both drugs begins with a “step-up dosing” schedule, a safety measure to help the body acclimate to the new therapy.
This initial phase involves receiving several smaller, escalating doses over about a week before the first full treatment dose. For teclistamab, this involves doses on day one, four, and seven, while talquetamab follows a similar schedule. This gradual introduction is done to mitigate the intensity of initial side effects.
Because of the risk of these reactions, the step-up dosing phase requires a hospital stay. Patients are monitored for at least 48 hours after each of the initial doses to manage any complications. After the step-up period and the first full dose, subsequent treatments are administered on a weekly or bi-weekly basis.
Understanding and Managing Side Effects
The mechanism of T-cell engaging therapies can lead to side effects, which are primarily a result of widespread immune system activation. The most notable of these are Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). Medical teams monitor for these conditions during the initial hospital stay.
CRS occurs when activated T-cells release a flood of inflammatory messengers called cytokines, leading to a systemic inflammatory response. Symptoms can range from mild, like fever and fatigue, to severe, including low blood pressure and difficulty breathing. ICANS is a neurological condition with symptoms like confusion, difficulty with speaking, and headache.
Management for both CRS and ICANS involves supportive care and specific medications to calm the immune response. While both drugs carry these risks, talquetamab has a unique set of side effects related to its GPRC5D target, as this protein is also found on healthy cells in the skin, nails, and oral cavity.
As a result, patients may experience skin-related issues like rashes, changes to their fingernails, and a condition called dysgeusia, which is an alteration in the sense of taste. These on-target, off-tumor effects are a difference in the side effect profile of talquetamab.
Choosing Between Teclistamab and Talquetamab
The decision to use teclistamab or talquetamab is made by a physician based on several clinical factors, with the patient’s prior treatment history being a primary consideration. Because the drugs have different molecular targets, they offer distinct strategic options for relapsed or refractory multiple myeloma.
A central factor is whether a patient has previously been treated with a therapy that targets BCMA. If a patient’s myeloma has relapsed after receiving a BCMA-directed treatment, their cancer may have developed resistance by reducing the amount of BCMA on the cell surface.
In this scenario, switching to talquetamab provides a new line of attack by targeting the GPRC5D protein, bypassing the BCMA resistance mechanism. The differing side effects of the two drugs also play a role in the decision-making process.
A patient’s overall health and personal tolerance for specific side effects are taken into account. For instance, the potential for skin, nail, and taste-related side effects with talquetamab might lead a physician to recommend teclistamab if those issues are a particular concern.