Talvey (talquetamab)

What Is Talvey?  

TALVEY® (also known as talquetamab-tvgs, the generic drug name, or "tal" for short) is a bispecific monoclonal antibody with a novel target, GPRC5D, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody. The FDA granted accelerated approval for Talvey's use in August 2023. 

Who Can Be Treated with Talvey?

In 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Talvey for the treatment of adults with relapsed/refractory multiple myeloma (RRMM), disease that has come back after a period of improvement. Myeloma patients can be treated with Talvey after 4 or more prior lines of therapy. The prior therapies must include the following:

• Proteasome inhibitor
  • Velcade® (bortezomib),
  • Kyprolis® (carfilzomib), or 
  • Ninlaro® (ixazomib).
• Immunomodulatory agent
  • Revlimid® (lenalidomide),
  • Pomalyst® (pomalidomide), or
  • Thalidomide.
• Anti-CD38 monoclonal antibody
  • Darzalex® (daratumumab),
  • Darzalex Faspro® (daratumumab + hyaluronidase fihj),
  • Sarclisa® (isatuximab), or
  • Sarclisa ESCENA™ (isatuximab-irfc)
     

How Does Talvey Work?  

Talvey uses a patient’s own immune system to fight their myeloma. Talvey is a bispecific antibody, an artificial antibody that binds to two (“bi”) targeted cells.  

Talvey is the first bispecific antibody approved by the FDA that targets G protein–coupled receptor, class C, group 5, member D (GPRC5D) and cluster of differentiation 3 (CD3) protein complex.  

A bispecific antibody has two “arms” that attach to two (“bi”) targeted cells. One arm binds to GPRC5D  on the surface of myeloma cells. The other arm binds to CD3 on the surface of the patient’s own immune system T cell (T lymphocyte). Next, Talvey activates the T cells to release toxic granules that kill the myeloma cells. 

Talvey is the first medication in the drug class of bispecific antibodies approved by the FDA that targets GPRC5D and CD3. 

How Does Talvey Differ from CAR T-cell Therapy?  

Talvey differs from CAR T-cell therapy in that there is no need to collect the patient’s T cells. Instead, Talvey engages the patient’s T cells directly after injection. Not having to collect, engineer, and manufacture T cells over the course of several weeks shortens the time-to-treatment for the myeloma patient.  

How Is Talvey Given?  

Talvey is given as an injection (“shot”) under the skin. This is called a subcutaneous injection. It is given by a healthcare professional under the skin in your stomach, thigh, or another area of the body.

How Has Talvey Been Used in Clinical Trials?  

MonumenTAL-1 clinical trial

Talvey received FDA approval based on the response rate and durability of response data from the MonumenTAL-1 clinical trial of single-agent Talvey in patients with RRMM. Nearly 75% of study patients were refractory to 5 drugs prior to being treated with Talvey. The study demonstrated an overall response rate (ORR) of more than 71% with weekly and every-other-week dosing of Talvey.

MonumenTAL-3 clinical trial

At the annual meeting of the European Hematology Association (EHA), the study selected for the EHA plenary session as one of the top research abstracts was MonumenTAL-3. The study compared the combination of Talvey and Darzalex (Tal-D) and Tal-D plus Pomalyst (Tal-DP) vs. Darzalex, Pomalyst, and dexamethasone (DPd) in patients with RRMM.

Among the two groups of patients receiving either Tal-D or Tal-DP, the benefits of progression-free survival (PFS) were seen across subsets that included older patients, patients with high-risk cytogenetics, those previously treated with Darzalex, and patients with soft tissue plasmacytomas.

At 2 years of follow-up, PFS rates for Tal-DP and Tal-D were 81.3% and 77.6%, respectively. Overall survival rates for Tal-DP and Tal-D were 89.2% and 87.9%, respectively.

PFS is the length of time during and after the treatment of myeloma that a patient lives with the disease, but the myeloma does not get worse. In a clinical trial, PFS is one way to measure how well the treatment is working
 

Extramedullary Disease (EMD)

One of the most challenging forms of myeloma is when the disease grows outside of the bone marrow. This is known as extra-medullary disease (EMD). Historically, myeloma patients with EMD had lower response rates to treatment. Patients with EMD tend to have very short periods of remission due to the aggressive nature of EMD. 

A clinical trial presented at the annual meeting of the American Society of Hematology (ASH) in December 2025 demonstrated remarkable results. The study combined two bispecific anti¬bodies with different targets on the myeloma cell: Talvey, which targets GPRC5D, and Tecvayli® (teclistamab-cqyv), which targets BCMA. Study patients with EMN had a response rate of 80%, nearly doubling prior therapies and lasting on aver¬age more than 12 months. This treatment is not yet approved by FDA.

Visit myeloma.org/sparkcures to research clinical trials near you.

How Will Talvey Be Made Available to Patients? 

Talvey is available only through a Risk Evaluation and Mitigation Strategy (REMS) .REMS programs are required by the FDA for treatments that may have serious safety concerns. REMS programs support the use of treatment and help ensure that the potential benefits outweigh the risks. 

Once taking Talvey, you will receive a Patient Wallet Card from your healthcare provider, which lists the signs and symptoms of possible complications. You must have the Patient Wallet Card with you at all times. Also, you must show it to all of your healthcare providers. 

How Should Talvey Be Dosed, and Scheduled? 

The IMF encourages patients to follow the dosing information on the manufacturer’s website here. The dose of Talvey is calculated based on the patient’s weight. The two step-up dosing schedules are designed to reduce the risk of side effects. Discuss the following 2 with your doctor. 

Talvey Weekly Dosing Schedule

Talvey Biweekly (Every 2 Weeks) Dosing Schedule

Your doctor will also decide the following:

• If you should be hospitalized for 2 days (48 hours) after receiving Talvey in order to reduce the risk of side effects. 
• The total number of treatments with Talvey you will receive.
• The number of days between your doses of Talvey.
• If you should be prescribed medicines to help reduce your risk of Talvey side effects.
   

What Warnings and Precautions Should Patients Undergoing Talvey Therapy Be Aware Of?  

Your doctor will decide how many treatments with Talvey you will receive, the number of days between your doses of Talvey, as well as any medicines you may receive to help reduce your risk of side effects. 

Due to the potential risks of Talvey, you may be hospitalized for 48 hours after all doses that are part of your “step-up dosing schedule” (when you receive the first 2 or 3 smaller “step-up” doses) and the first full treatment dose. Step-up doses are used to mitigate the risk of potential side effects. 

The toxicity criteria adopted in the United States by the National Cancer Institute (NCI) for cancer clinical trials includes Grade 0 (no symptoms), Grade 1 (mild symptoms), Grade 2 (moderate symptoms), Grade 3 (symptoms requiring treatment), and Grade 4 (symptoms requiring urgent intervention).  

In the MonumenTAL-1 study, GPRC5D-associated side effects were shown to be clinically manageable with appropriate identification, monitoring, and treatment.  

Cytokine Release Syndrome (CRS) 

Cytokines are proteins that circulate in the bloodstream, usually in response to infection, that can stimulate or inhibit the growth or activity in other cells.

CRS is a potentially fatal, uncontrolled immune reaction in which cytokines become highly elevated and trigger an overwhelming immune system response. A cytokine storm can seriously damage body tissues and organs.

CRS occurred in 76% of patients who received Talvey at the recommended dosages in the MonumenTAL-1 study. The Grade criteria adopted in the United States by the National Cancer Institute (NCI) to measure toxicity in cancer clinical trials includes:

• Grade 1 – mild symptoms, 57% of study patients.
• Grade 2 – moderate symptoms, 17% of study patients.
• Grade 3 – symptoms requiring treatment, 1.5% of study patients.

At the recommended dosages, recurrent CRS occurred in 30% of study patients. Most events occurred following step-up dose 1 (29%) or step-up dose 2 (44%). With the biweekly dosing schedule, CRS occurred in 33% of patients with step-up dose 3.

CRS occurred in 30% of patients with the first 0.4 mg/kg treatment dose and in 12% of patients treated with the first 0.8 mg/kg treatment dose. The CRS rate for both dosing schedules combined was less than 3% for each of the remaining doses in Cycle 1 and less than 3% cumulatively from Cycle 2 onward.

The median time to onset of CRS was 27 hours from the last dose, and the median duration was 17 hours.
 

Immune effector cell-associated neurotoxicity syndrome (ICANS)  

ICANS can occur in the days or weeks after the administration of immunotherapy, especially immune effector cell (IEC) and T-cell therapies. Neurotoxicity (also known as neurologic toxicity) occurs when exposure to toxic substances changes the normal activity of the nervous system.

In the MonumenTAL-1 study, neurologic toxicity occurred in 55% of patients who received Talvey at the recommended dosages, with Grade 3 or 4 neurologic toxicity occurring in 6% of patients. The most frequent neurologic toxicities were the following:

• Headache (20%), 
• Encephalopathy (15%), 
• Sensory neuropathy (14%), and 
• Motor dysfunction (10%).

ICANS was reported in 9% of 265 patients who received Talvey at the recommended dosages in phase II of the MonumenTAL-1 study. Recurrent ICANS occurred in 3% of study patients as follows:

• Following step-up dose 1 (3%), 
• Following step-up dose 2 (3%), 
• Following step-up dose 3 of the biweekly dosing schedule (1.8%),
• The initial treatment dose of the weekly dosing schedule (2.6%), or
• The biweekly dosing schedule (3.7%). 

The median time to onset of ICANS was 2.5 days after the most recent dose with a median duration of 2 days. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.

The use of prophylaxis reduces CRS and ICANS

Research was presented at the ASH annual meeting in December 2024 on the use of tocilizumab (“toci” for short) in patients treated with bispecific antibodies. Toci blocks the interleukin-6 (IL-6) receptor, a cytokine that causes inflammation.

A total of 72 study patients, including 16 patients treated with Talvey, received toci with the first step-up-dose of a bispecific antibody. Investigators recorded a low rate of CRS (20%) and ICANS (19%) in the Talvey patients. The rate of recurrence for CRS and ICANS was 0% and 1%.
 

Infections 

The incidence of severe infections was lower when compared to treatments that target B-cell maturation antigen (BCMA). Preventive measures and management strategies are consistent with non-BCMA-directed therapies for myeloma. In the MonumenTAL-1 study, serious infections occurred in 16% of patients, with fatal infections in 1.5% of patients. Grade 3 or 4 infections occurred in 17% of patients. The most common serious infections reported were bacterial infection (8%, including sepsis).

Vaccinations are important, especially for immunocompromised individuals and their care partners. Ask your doctor which new or updated vaccines are recommended in your case.
 

Cytopenias  

Talvey can cause cytopenias, including neutropenia and thrombocytopenia. In the MonumenTAL-1 study, Grade 3 or 4 decreased neutrophils occurred in 35% of patients. Grade 3 or 4 decreased platelets occurred in 22% of patients. The median time to onset for Grade 3 or 4 neutropenia was 22 days, and the median time to resolution to Grade 2 or lower was 8 days. The median time to onset for Grade 3 or 4 thrombocytopenia was 12 days, and the median time to resolution to Grade 2 or lower was 10 days.

Prophylaxis with bispecific antibodies

Research was presented at the ASH annual meeting in December 2024 on the use of tocilizumab (“toci” for short) in patients treated with bispecific antibodies. Toci blocks the interleukin-6 (IL-6) receptor, a cytokine that causes inflammation.

A total of 72 study patients, including 16 patients treated with Talvey, received toci with the first step-up-dose of a bispecific antibody. Investigators recorded a low rate of CRS (20%) and ICANS (19%) in the Talvey patients. The rate of recurrence for CRS and ICANS was 0% and 1%.
 

Hepatotoxicity  

Talvey can cause hepatotoxicity (injury to the liver or impairment of liver function). Liver enzyme elevation can occur with or without concurrent CRS. Bilirubin and liver enzymes should be tested at baseline and during treatment. In the MonumenTAL-1 study:

• Elevated alanine aminotransferase (ALT) blood test results occurred in 33% of patients, with Grade 3 or 4 ALT elevation occurring in 2.7%. 
• Elevated aspartate aminotransferase (AST) occurred in 31% of patients, with Grade 3 or 4 AST elevation occurring in 3.3%. 
• Grade 3 or 4 elevation of total bilirubin occurred in 0.3% of patients. 
    

Embryo-fetal toxicity  

Women of reproductive potential and males with female partners of reproductive potential must use effective contraception during treatment with Talvey and for at least 3 months after the last dose. Ask your doctor which effective contraception method should be used.

Due to the potential for harm in the breastfed child, lactating women should not breastfeed during treatment and for a period of time after treatment ends. 
 

When to seek medical help

Immediately alert your doctor or seek medical help if you develop any of the symptoms listed below or if you experience any other potential side effects of Talvey: 

• fever (100.4°F or higher) 
• feeling anxious 
• dizziness or lightheadedness 
• headache 
• chills 
• fast heartbeat, 
• difficulty breathing 
• feeling very sleepy with low energy 
• feeling confused or disoriented 
• being less alert or aware 
• slow or difficulty thinking 
• seizures 
• trouble speaking or writing 
• muscle weakness 
• shaking (tremors) 
• memory loss 
• numbness and tingling (feeling “pins and needles”) 
• burning, throbbing, or stabbing pain 

What Are Possible Common Side Effects of Talvey? 

Talvey can cause adverse effects in the mouth and throat. This is due to Talvey targeting the GPRC5D protein, which is also present in healthy tissues, including tongue and salivary glands. This may cause mouth discomfort, sores, inflammation, redness, and/or the following:

• Distortion or loss of taste (approx. 71% to 72% of study patients)
• Dry mouth due to reduced production of saliva (27% to 40% of patients)
• Difficulty or pain when swallowing (24% to 25% of patients)

In most clinical trial patients, median time to onset of oral side effects was 15–29 days. Median duration of oral side effects was 57–109 days.

Resolution of oral side effects was achieved in 31%–73% of patients. Oral side effects were managed with dose reduction in fewer than 9% of study patients. If oral side effects continued, their severity was mostly reduced to Grade 1 or 2.

In fewer than 2% of study patients, treatment with Talvey was discontinued.

Nutritional support: Ask your doctor for a referral to a nutritionist or dietician. Given the possibility of oral side effects described above, you might benefit from nutritional management and supportive measures. Make sure that you are monitored for weight loss.

IMF Nurse Leadership Board (NLB) member Donna Catamero, ANP-BC, OCN®, CCRC (Mount Sinai Health System, New York) presented the poster “Practical Management of Patients with Relapsed/Refractory Multiple Myeloma Receiving Talquetamab” at the 2023 International Myeloma Society (IMS) meeting in Athens, Greece. Donna’s report is summarized below.  

Skin-related toxicities

The following Grade 1 or 2 rash and non-rash skin-related side effects were experienced by 30%–73% clinical trial participants:

• Dryness,
• Itchiness, 
• Exfoliation, peeling, or flaking,
• Hand-foot syndrome (palmar-plantar erythrodysesthesia)

For most patients experiencing ski-related toxicity, median time to onset was 20 to 30 days. Median duration was 26 to 39 days for most patients. Resolution was seen in 57%–88% of skin-related events. Most skin-related side effects can be managed with:

• Heavy moisturizers and hydration.
• Topical steroids can be used to control inflammation, irritation, and redness.
• Oral steroids can help if you experience severe skin-related toxicity. 
   

Nail-related toxicities

The incidence of nail-related side effects in study patients was 54%–55% and was mostly Grade 1 or 2. This included:

• Onycholysis (when the nail separates from the nail bed), 
• Onychomadesis (painless nail shedding), 
• Onychoclasis (the breaking or splitting of nails),
• Dystrophy (abnormal change in the shape, color, texture, or growth) of fingernails and/or toenails. 
   

For most patients, median time to onset was 68 to 69 days, and median duration was 74 to 89 days. Resolution was seen in 26%–33% of events.

Dose modification was needed in fewer than 1% of patients. There was no treatment discontinuation due to nail-related side effects.

Comfortable shoes, soft socks, good hygiene, keeping nails trimmed, and using moisturizers and/or topical corticosteroids may be helpful.
 

Talvey Assistance Program

If you are prescribed Talvey, you can sign up for the “TALVEY withMe: Personalized 1-on-1 Support.” Visit talvey.com or call 1.833.565.9631 Monday through Friday, 8 a.m. – 8 p.m. (ET) to connect one-on-one with a Care Navigator to explore cost, education, and resources at no cost to you.

Your Care Navigator can help guide you to support solutions throughout your treatment journey with Talvey.