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You are not alone
The International Myeloma Foundation (IMF) is here to help you. The IMF is committed to providing information and support for patients with multiple myeloma (which we refer to simply as “myeloma”) and their care partners, friends, and family members.
We achieve this through a broad range of resources available on our website myeloma.org, and through numerous programs and services such as seminars, webinars, workshops, and the IMF InfoLine, which consistently provides the most up-to-date and accurate information about myeloma in a caring and compassionate manner. Contact the IMF InfoLine at 1.818.487.7455 or InfoLine@myeloma.org.
What you will learn from this booklet
Myeloma is a cancer that is not known to most patients at the time of diagnosis. If you have myeloma, it is important and helpful for you to learn about your disease, its treatment options, and supportive care measures in order to play an active role in your own medical care and to make good decisions about your care in partnership with your doctor.
If you are a patient with myeloma, we suggest that you read the IMF’s publication, Patient Handbook for Multiple Myeloma, which will help you to better understand this disease. In addition, this booklet will direct you to resources that may be relevant in your particular case. All IMF publications are free-of-charge and can be read, downloaded, or requested in printed format at publications.myeloma.org.
The IMF’s Understanding-series publications address specific drugs, drug classes, and combination therapies used to treat myeloma. These booklets also discuss supportive care measures that may help manage the symptoms and side effects of myeloma and its treatments. The IMF’s publication, Understanding Your Test Results, explains how myeloma is diagnosed, monitored, and assessed throughout the disease course.
Words in bold+blue type are explained in the IMF’s companion publication, Understanding Myeloma Vocabulary, a comprehensive glossary that also can be helpful in discussions with your doctor. Myeloma is complicated, but the language that describes it doesn’t have to be hard to understand.
If you are reading this booklet in electronic format, the light blue links will take you to the corresponding resources. This booklet discusses Talvey® (also known as talquetamab-tgvs, its generic drug name). Talvey is a first-in-class bispecific antibody approved by the U.S. Food and Drug Administration (FDA) in August 2023 for adult patients with relapsed or refractory multiple myeloma (RRMM).
Indication for the use of Talvey
In August 2023, Talvey was granted accelerated approval by the FDA for the treatment of adult patients with RRMM who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent , and an anti-CD38 monoclonal antibody.
How Talvey works
Talvey employs 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.
Clinical trial experience with Talvey
A clinical trial is a medical research study with people who volunteer to test scientific approaches to a new treatment or a new combination therapy. Each clinical trial is designed to find better ways to prevent, detect, diagnose, or treat cancer and to answer scientific questions.
to
Talvey binds to GPRC5D on the myeloma cell surface
GPRC5D tumor-speci c surface antigens
activates the T cell to release cytotoxic granules that kill the myeloma cell
Talvey received the FDA approval 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. Nearly 75% of patients who participated in this study were refractory to 5 drugs prior to being treated with Talvey. The MonumenTAL-1 clinical trial demonstrated an overall response rate (ORR) of more than 71% with weekly and every-other-week dosing of Talvey.
Finding a clinical trial to match your needs
The IMF has partnered with SparkCures to help myeloma patients discover and explore clinical trials across the U.S. that best match their needs. To identify a clinical trial personalized to your preferences, visit myeloma.org/sparkcures or contact the IMF InfoLine. For information about all clinical trials with Talvey in various myeloma disease settings and drug combinations, you can also visit clinicaltrials.gov.
Important safety information
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 also the first full treatment dose. Step-up doses are used to mitigate risk of potential side effects.
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)
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 Grade 1 CRS occurring in 57% of patients, Grade 2 in 17%, and Grade 3 in 1.5%. Recurrent CRS occurred in 30% of patients. Most events occurred following step-up dose 1 (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 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 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 patients. Most patients experienced ICANS following step-up dose 1 (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 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-BCMAdirected 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 (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
Talvey may cause fetal harm. 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 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.
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.
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 incidence of dysgeusia (a distortion of the sense of taste) was shown to be 71%–72%, dry mouth 27%–40%, and 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 (e.g., food texture/flavor experimentation, increased hydration, artificial saliva spray, mouth rinse, dexamethasone mouthwash, anti-infection agents, and vitamin support) to restore interest in food. 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 Grade 1 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 onycholysis, onychomadesis, onychoclasis, discoloration, disorder, dystrophy, and 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.
Prophylaxis for treatment with bispecifics
In December 2024, at the annual meeting of the American Society of Hematology (ASH), data was presented on the use of tocilizumab as prophylaxis for RRMM patients treated with bispecific antibodies, including Talvey. In this study by Dr. Andrew Kowalski and colleagues, tocilizumab was given prior to the first step-up-dose of any of the three FDA-approved bispecifics.
Given as an injection or infusion, tocilizumab blocks the interleukin-6 (IL-6) receptor, a cytokine that causes inflammation. Of the 72 study patients who received prophylactic tocilizumab, 16 were treated with Talvey. Investigators observed 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%.
Prior studies that investigated the use of prophylactic tocilizumab before Talvey, as well as emerging real-world evidence, indicate that tocilizumab may be effective as a preventative (rather than reactive) measure for patients treated with a bispecific antibody for RRMM. Larger randomized studies are needed.
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.
In closing
This booklet is not meant to replace the advice of your doctors and nurses who are best able to answer questions about your specific healthcare management plan. The IMF intends only to provide you with information that will guide you in discussions with your healthcare team.
To help ensure a good quality of life through effective treatment of your myeloma, you must play an active role in your own medical care. We encourage you to visit myeloma.org for more information and to join the Myeloma Knowledge Platform at myprofile.myeloma.org.
To receive the most up-to-date information about myeloma in a caring and compassionate manner, call the IMF InfoLine at 1.818.487.7455, email InfoLine@myeloma.org, or schedule a time to talk with an IMF InfoLine Coordinator at mmsm.link/infoline.
To get answers to your questions without having to wait, ask Myelo® anytime 24/7 at myeloma.org. This generative AI assistant is designed to help you find the right resources.
Use the hyperlinks and web addresses included in this publication for quick access to resources from the IMF. Sign up at subscribe.myeloma.org for our quarterly journal Myeloma Today and weekly e-newsletter Myeloma Minute, as well as alerts about IMF news, events, and actions.
The International Myeloma Foundation (IMF) is the global leader in myeloma. Our mission is to improve the quality of life of myeloma patients while working toward prevention and a cure. Since 1990, the IMF has been serving the myeloma community through the following four pillars:
RESEARCH At the IMF, finding a cure for myeloma is our top priority. The IMF Scientific Advisory Board (SAB) of leading myeloma experts identifies key opportunities to drive research forward. The IMF Black Swan Research Initiative® (BSRI®) is pushing the boundaries with early screening for a precursor condition of myeloma as well as cure-focused myeloma clinical trials. The IMF International Myeloma Working Group (IMWG) provides trusted guidelines for diagnosing, treating, and managing myeloma. We also fund innovative research through the IMF Brian D. Novis Research Grants.
EDUCATION Myeloma is a complex and unique journey for each patient. The IMF offers hundreds of videos and free publications in multiple languages to inform and empower patients and care partners to navigate their myeloma journey. All IMF seminars, webinars, and workshops are free-of-charge and designed to directly connect the patient community with expert myeloma clinicians. The IMF Nurse Leadership Board (NLB) provides recommendations for the management of myeloma. The IMF M-Power Project works to break down barriers and ensure health equity in underserved populations.
SUPPORT Studies show that social support can greatly improve the quality of life of people with cancer. The IMF offers more than 160 myeloma support groups across North America, including specialized groups for Spanish-speakers, people with smoldering myeloma, care partners of patients with myeloma, and patients who do not have care partners. The IMF InfoLine answers myeloma-related questions. Myelo®, the IMF’s generative AI assistant, is available 24/7 to help you find the right resources.
ADVOCACY In the U.S., the IMF Advocacy team represents your interests at the federal and state levels. Internationally, the IMF Global Myeloma Action Network (GMAN) works to improve patient access to treatments.