Talvey (talquetamab)

What Is Talvey?  

TALVEY™ (also known as talquetamab, the generic drug name) 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. 

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.  

Talvey has two “arms," one arm attaching to the myeloma cell through the GPRC5D on the cell surface and one arm attaching to CD3 on the surface of a local T cell (T lymphocyte) and activating that T cell to destroy the myeloma cell. GPRC5D has been identified as an immunotherapeutic target in myeloma treatment. It is overexpressed on myeloma cells but has limited expression on normal hematopoietic cells, such as B cells (B lymphocytes) and bone marrow progenitor cells (which can differentiate into specific cell types). The CD3 protein complex is involved in activating the T cell to release cytotoxic granules that kill the myeloma cell. 

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.  

When Should Talvey Be Used as a Treatment?  

Talvey is FDA-approved for patients with relapsed or refractory myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.  

How Has Talvey Been Used in Clinical Trials?  

The phase I/II MonumenTAL-1  

Talvey received accelerated approval from the FDA based on the response rate and durability of response data from the open-label, single-arm, phase I/II MonumenTAL-1 clinical trial of Talvey in patients with RRMM.  

The goal of conducting myeloma clinical trials is to improve patient care by determining if a new drug or treatment is more effective and/or has fewer or less harmful side effects than existing treatments. A clinical trial is a medical research study undertaken only after laboratory studies have shown the potential of a new drug to work better than existing methods and have outlined the potential safety. Clinical trial participants are people who volunteer to test scientific approaches to a new treatment or a new combination therapy. 

The MonumenTAL-1 study demonstrated an overall response rate (ORR) of more than 71% with weekly and every-other-week dosing of Talvey in patients with RRMM. Nearly 75% of patients were refractory to 5 drugs before being treated with Talvey. However, it is too early to estimate the response duration (DOR). Myeloma patients treated with Talvey report sustained clinically meaningful improvements in quality of life, consistent with outcomes in the MonumenTAL-1 study. 

How Will Talvey Be Made Available to Patients? 

Talvey is available only through a Risk Evaluation and Mitigation Strategy (REMS). You will receive a Patient Wallet Card from your healthcare provider, which lists the signs and symptoms of CRS and neurologic problems. You must have the Patient Wallet Card with you at all times – show it to all of your healthcare providers. 

How Should Talvey Be Administered, Dosed, and Scheduled? 

The IMF encourages patients to follow the dosing information on the manufacturer’s website here.  

Talvey Weekly Dosing Schedule

Dosing schedule	Day	Dose	Dose
Step-up dosing	Day 1	Step-up dose 1	0.01 mg/kg
Step-up dosing	Day 4	Step-up dose 2	0.06 mg/kg
Step-up dosing	Day 7	First treatment dose	0.4 mg/kg
Weekly dosing schedule	One week after first treatment dose and weekly thereafter	Subsequent treatment doses	0.4 mg/kg once weekly

Talvey Biweekly (Every 2 Weeks) Dosing Schedule

Dosing schedule	Day	Dose	Dose
Step-up dosing	Day 1	Step-up dose 1	0.01 mg/kg
Step-up dosing	Day 4	Step-up dose 2	0.06 mg/kg
Step-up dosing	Day 7	Step-up dose 3	0.4 mg/kg
Step-up dosing	Day 10	First treatment dose	0.8 mg/kg
Weekly dosing schedule	One week after first treatment dose and weekly thereafte	Subsequent treatment doses	0.8 mg/kg every two weeks

 

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) 

Cytokine Release Syndrome (CRS) CRS is a potentially severe or fatal uncontrolled immune reaction in which cytokines become highly elevated and trigger an overwhelming immune system response that can damage body tissues and organs. 

In the MonumenTAL-1 study, CRS occurred in 76% of patients who received Talvey at the recommended dosages, with Grade1 CRS occurring in 57% of patients, Grade 2 in 17%, and Grade 3 in1.5%. Recurrent CRS occurred in 30% of patients. Most events occurred following step-up dose1 (29%) or step-up dose 2 (44%) at the recommended dosages. CRS occurred in 33% of patients with step-up dose 3 in the biweekly dosing schedule. 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 Cycle1 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%) 
• 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 patients. Most patients experienced ICANS following step-up dose1 (3%), step-up dose 2 (3%), step-up dose 3 of the biweekly dosing schedule (1.8%), or 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 the resolution of CRS, or in the absence of CRS.  

Infections 

The incidence of severe infections was lower with Talvey 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), and COVID-19 (2.7%). 

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, and Grade 3 or 4 decreased platelets occurred in 22% of patients who received Talvey. 

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. 

Hepatotoxicity  

Talvey can cause hepatotoxicity, which is defined as injury to the liver or impairment of liver function. 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 elevations of total bilirubin occurred in 0.3% of patients. Liver enzyme elevation can occur with or without concurrent CRS. Bilirubin and liver enzymes should be tested at baseline and during treatment.  

Embryo-fetal toxicity  

Exposure of an embryo or a fetus to Talvey may cause fetal harm when administered to a pregnant woman. Females of reproductive potential and males with female partners of reproductive potential must use effective contraception during treatment with Talvey and for 3 months after the last dose.

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? 

GPRC5D-related side effects also include oral, skin, and nail toxicities. Dentists, nutritionists, and dermatologists may be able to provide additional guidance about managing the side effects and to confirm if the side effects are related to treatment with Talvey.  

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.  

Oral toxicity  

Oral toxicity was managed with dose modifications in fewer than 9% of study patients, and treatment discontinuation in fewer than 2% of study patients. Oral side effects may persist over time, but severity was mostly Grade 1 or 2.  

The following summarizes the incidences of certain side effects of Talvey: 

• dysgeusia (a distortion of the sense of taste) was shown to be 71%–72% 
• dry mouth 27%–40% 
• dysphagia (difficulty in swallowing) 24%–25% 

Median time to onset of oral side effects was 15–29 days for most patients, median duration was 57–109 days for most patients, and resolution of oral side effects was achieved in 31%–73% cases.  

Nutritional supportive measures and management  

Nutritional supportive measures and management may be required.  

Examples of nutritional support to restore interest in food include the following: 

• food texture/flavor experimentation 
• increased hydration 
• artificial saliva spray 
• mouth rinse 
• dexamethasone mouthwash 
• anti-infection agents 
• vitamin support 

Patients should be monitored for weight loss, which may affect concurrent medications. 

Skin-related toxicities  

Most skin-related toxicities can be managed with heavy moisturizers and hydration.  

Topical corticosteroids can be used to control inflammation, irritation, and redness. 

Oral corticosteroids may be used for severe events.  

Incidence of skin-related side effects in the study with rash and non-rash (exfoliation, dry skin, palmar-plantar erythrodysesthesia, and pruritis) was 30%–73%, and severity was mostly Grade1 or 2.  

Median time to onset was 20 to 30 days for most patients, median duration was 26 to 39 days for most patients, and resolution of skin-related side effects was seen in 57%–88% of events. 

Nail-related toxicities  

The incidence of nail-related side effects in the study was 54%–55% and included the following: 

• onycholysis 
• onychomadesis 
• onychoclasis 
• discoloration 
• disorder 
• dystrophy 
• ridges 

Severity was mostly Grade 1 or 2. Median time to onset was 68 to 69 days for most patients, median duration was 74 to 89 days for most patients, and resolution was seen in 26%–33% of events.  

Dose modification was needed in less than 1% of events, and there was no treatment discontinuation due to nail-related side effects. Comfortable shoes, soft socks, good hygiene, and treatment with moisturizers and/or topical corticosteroids may be considered.