Talquetamab

Talquetamab-tgvs (Talvey) is a prescription medicine used to treat relapsed or refractory multiple myeloma, a type of bone marrow cancer. It is a bispecific antibody that binds to both myeloma cancer cells and T cells, a key part of the immune system. By linking these cells together, talquetamab helps activate the patient’s own immune system to target and destroy multiple myeloma cells. Talquetamab is used in adults when their multiple myeloma has not responded to treatment (refractory) or has come back after treatment (relapsed).

Talquetamab FDA approval was granted on August 9, 2023, by the Janssen Pharmaceutical Companies of Johnson & Johnson. Talquetamab brand name is Talvey.

Talquetamab FDA approval is for the treatment of adults with:

• Relapsed or refractory multiple myeloma
• Have already received at least 4 different treatment regimens, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Talquetamab is a GPRC5D-directed CD3 T-cell engager.

Talquetamab mechanism of action (MOA) is by targeting and binding to GPRC5D, a protein found on multiple myeloma cells, and CD3, a protein complex on the surface of T cells. Once Talvey binds to both targets, it activates the T cell, prompting it to release cytotoxic granules that destroy the myeloma cell.

In the MonumenTAL-1 study, talquetamab demonstrated its effectiveness in pretreated multiple myeloma patients:

Weekly dose 0.4 mg/kg:

• Overall Response Rate (ORR): 73% of patients achieved a significant reduction in disease burden.
• Duration of Response (DOR): an estimated 85% of responders maintained response for at least 9 months, with the median DOR not yet reached at the time of analysis

Biweekly dose 0.8 mg/kg (Every 2 Weeks):

• Overall Response Rate (ORR): 73.6% of patients achieved a significant reduction in disease burden. (dose 0.4 mg/kg Weekly)
• Duration of Response (DOR): was not estimable

Talquetamab is given as a subcutaneous injection at a healthcare facility, with dosing schedules that can be either weekly or biweekly (every two weeks). The treatment begins with a step-up phase to reduce potential side effects:

Step-Up Phase: Patients receive incremental doses to allow the body to adjust to the medication.

Treatment Phase: Following the step-up phase, the maintenance dose is administered either weekly or twice weekly.

General administration information

• Talquetamab will be given to you by your healthcare provider as an injection under your skin (subcutaneous injection), usually in the stomach area (abdomen). Talvey may also be injected into your thigh or another area of your body.
• You will need to stay in the hospital for 48 hours after some doses of talquetamab. Talk with your doctor if you have any questions.
• You may be given other medications to help prevent serious side effects or allergic reaction. Keep taking these medicines for as long as your doctor has prescribed.
• Your treatment with Talvey may be temporarily or permanently discontinued if you have certain side effects.
• You will need medical tests before and during treatment with this medicine.
• If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment.

Talquetamab may cause side effects that are serious, life-threatening, or lead to death, including Cytokine Release Syndrome (CRS) and neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).

Call your healthcare provider or get medical help right away if you develop any of the signs or symptoms of CRS or neurologic problems listed below at any time during your treatment with this medicine:

Cytokine Release Syndrome (CRS)

CRS is common during treatment with this medicine and can also be serious or life-threatening. Signs and symptoms of CRS may include:

• fever (100.4°F or higher)
• dizziness or lightheadedness
• chills
• difficulty breathing
• feeling anxious
• headache
• fast heartbeat

Neurologic problems

Symptoms of neurologic problems with Talquetamab may include:

• headache
• feeling confused
• being less alert or aware
• feeling disoriented
• trouble speaking or writing
• shaking (tremors)
• numbness and tingling (feeling like “pins and needles”)
• feeling sleepy
• feeling very sleepy with low energy
• slow or difficulty thinking
• seizures
• muscle weakness
• memory loss
• burning, throbbing, or stabbing pain

Due to the risk of CRS and neurologic problems, you should be hospitalized for 48 hours after all doses of Talvey that are part of the “step-up dosing schedule”. The “step-up dosing schedule” is when you receive the first 2 or 3 doses, which are smaller “step-up” doses, and also the first full “treatment dose”.

Before you receive talquetamab, tell your healthcare provider about all of your medical conditions, including if you:

• have an infection

Females and Pregnancy

Tell your healthcare provider if you are pregnant or plan to become pregnant. Talquetamab-tgvs may harm your unborn baby. Tell your healthcare provider if you become pregnant or think that you may be pregnant during treatment with talquetamab.

Females who are able to become pregnant:

• Your healthcare provider should do a pregnancy test before you start treatment with Talvey.
• You should use effective birth control (contraception) during treatment and for 3 months after your last dose of talquetamab.

Breastfeeding

Tell your healthcare professional if you are breastfeeding or plan to breastfeed. It is not known if Talvey passes into your breast milk. Do not breastfeed during treatment and for 3 months after your last dose of Talvey.

Common talquetamab side effects

Common talquetamab side effects may include:

• Fever (83%)
• Fatigue or tiredness (37%)
• Cytokine release syndrome - CRS (76%)
• Changes in your sense of taste (70%)
• Nail disorder (50%)
• Muscle and joint pain(43%)
• Skin Disorder (41%)
• Rash (38%)
• Weight loss (35%)
• Dry mouth (34%)
• Severely dry skin (30%)
• Itchy skin (30%)
• Difficulty swallowing (23%)
• Upper respiratory tract infection (22%)
• Diarrhea (21%)
• Low blood pressure (21%)
• Headache (21%).

Laboratory abnormalities were also a common side effect.

These common side effects occurred in 20% or more of patients in the MonumenTAL-1 Talvey clinical trial (NCT03399799).

Serious talquetamab side effects

Get emergency medical help if you have signs of an allergic reaction: hives, difficulty breathing, and swelling of your face, lips, tongue, or throat.

Tell your medical caregivers if you have signs of cytokine release syndrome (CRS), a serious side effect fever, chills, trouble breathing, confusion, severe vomiting or diarrhea, fast or irregular heartbeats, feeling light-headed or very tired.

You may get infections more easily, even serious or fatal infections. Call your doctor right away if you have signs of infection such as:

• fever, chills, sore throat;
• mouth sores, red or swollen gums;
• pain or burning when you urinate;
• pale skin, easy bruising, unusual bleeding; or
• chest discomfort, wheezing, dry cough or hack, rapid weight loss.

Talquetamab may cause other serious side effects. Call your doctor at once if you have:

• mouth problems or weight loss;
• rash, skin redness, or red bumps;
• low blood cell counts - fever, chills, tiredness, mouth sores, skin sores, pale skin, cold hands, and feet, feeling light-headed or short of breath;
• neurological problems - headache, jerking muscle movements, rigid muscles, feeling restless, numbness and tingling, confusion, problems speaking, muscle spasms, tremors, double vision, changes in handwriting, problems walking, muscle weakness in body or face, hearing loss, burning, throbbing, or stabbing pain; or
• liver problems - loss of appetite, stomach pain (upper right side), tiredness, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Talquetamab is only available through the Talvey Risk Evaluation and Mitigation Strategy (REMS) program due to the risk of cytokine release syndrome (CRS) and neurologic complications, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). This program is designed to minimize the risk of serious CRS and neurological side effects in patients.

To ensure safety, prescribers, pharmacies, and healthcare facilities must be enrolled and certified in the REMS program. This certification ensures that healthcare providers receive proper training and that treatment facilities meet the required safety standards.

You will receive a Patient Wallet Card from your healthcare provider. Carry the Patient Wallet Card with you at all times and show it to all of your healthcare providers. The Patient Wallet Card lists signs and symptoms of CRS and neurologic problems.

Get medical help right away if you develop any of the signs and symptoms listed on the Patient Wallet Card. You may need to be treated in a hospital. If you have any questions about this medicine, ask your healthcare provider. Your healthcare provider may temporarily stop or completely stop your treatment if you develop CRS, neurologic problems, or any other severe side effects.

Talquetamab dose

Talquetamab dose is based on body weight.

Talquetamab is given weekly or every 2 weeks. Your healthcare provider will decide the number of days to wait between your doses of this medicine as well as how many treatments you will receive.

• If you receive your dose, “Step-up dose 1” is given on day 1 of treatment. “Step-up dose 2” is usually given on day 4 of treatment. The first “treatment dose” is usually given on day 7 of treatment.
• If you receive your dose every 2 weeks, “Step-up dose 1” is given on day 1 of treatment. “Step-up dose 2” is usually given on day 4 of treatment. “Step-up dose 3” is usually given on day 7 of treatment. The first “treatment dose” is usually given on day 10 of treatment.

If your dose is delayed for any reason, you may need to repeat the “step-up dosing schedule” to receive talquetamab. Before each “step up” dose, you will receive medicines to help reduce your risk of CRS. Your healthcare provider will decide if you need to receive medicines to help reduce your risk of CRS with future doses. Your healthcare provider will monitor you for signs and symptoms of CRS, neurologic problems, as well as other side effects and treat you as needed.

Do not drive, operate heavy machinery, or do other dangerous activities during and for 48 hours after your talquetamab “step-up dose” is completed or at any time during treatment with Talvey, if you develop dizziness, confusion, tremors, sleepiness, or any other symptoms that impair consciousness until your signs and symptoms go away. These may be signs and symptoms of CRS or neurologic problems.

Sometimes it is not safe to use certain medicines at the same time. Some drugs can affect your blood levels of other drugs you use, which may increase side effects or make the medicines less effective.

Other drugs may affect talquetamab, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all other medicines you use.

Talquetamab J-code is J3055 (talquetamab-tgvs, 0.25 mg). J codes are used for medicines that are not taken orally and include injections, inhalations chemotherapies. J codes are important for accurate and consistent coding for billing and reimbursement purposes.

Your physician will need the talquetamab J-code when filling out forms for your treatment.

HCPs and patients often use the Talquetamab Package Insert (Talvey) for more detailed information about this medicine. The Talvey Package Insert contains more comprehensive information on Indications and Usage, Dosage and Administration, Clinical Pharmacology, Clinical Studies, Drug Interaction, and more. Discuss any medical questions you have with your HCP (health care professional). This is not all the information you need to know about this medicine for safe and effective use, and it does not take the place of talking to your doctor about your treatment.

The Package Insert is sometimes called Talvey Prescribing Information (PI) or FDA label.

Active ingredient: talquetamab-tgvs Talvey brand Inactive ingredients: edetate disodium, glacial acetic acid, polysorbate 20, sodium acetate, sucrose, and Water for Injection, USP.

Talvey manufacturer Janssen Biotech, Inc., Horsham, PA 19044, USA