TALVEY (talquetamab-tgvs) Approved By FDA

FDA approves the first bispecific antibody targeting GPRC5D and CD3 in patients with RRMM 

By Dr. Joseph Mikhael, IMF Chief Medical Officer 


On August 9, 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Talvey™ (talquetamab-tgvs) for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The approval was based on data from the open-label, single-arm, phase I/II MonumenTAL-1 clinical trial of Talvey in patients with RRMM. 

Talvey is the only approved bispecific antibody targeting G protein-coupled receptor family C group 5 member D (GPRC5D), which is overexpressed on myeloma cells but has limited expression on normal hematopoietic cells (e.g., B cells, bone marrow progenitors). Myeloma patients treated with Talvey report sustained clinically meaningful improvements in quality of life, consistent with outcomes in the MonumenTAL-1 study. 

The term “bispecific” means that Talvey has two “arms,” with one arm attaching to the myeloma cell through the GPRC5D on the cell surface and one arm attaching to and activating a local T cell to destroy the myeloma cell. Talvey employs a patient’s own immune system to fight their myeloma. 

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. Indeed, nearly 75% of patients were refractory to 5 drugs when treated with Talvey. At this time, it is too early to estimate the duration of response (DOR).  

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. 

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. Step-up doses were used to mitigate risk of high-grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Close monitoring for CRS and ICANS is important during step-up dosing and the first full dose 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 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 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. 
  • 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 20–30 days for most patients, median duration was 26–39 days for most patients, and resolution of skin-related side effects was seen in 57–88% of events. 
  • 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 68–69 days for most patients, median duration was 74–89 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. 

All treatment centers that provide Talvey must adhere to a Risk Evaluation and Mitigation Strategy (REMS) program that monitors the risks of treatments. 

It is very exciting news that patients with RRMM now have another treatment option with a high response rate and a new target to fight their myeloma.  

See the Spring 2022 edition Myeloma Today to read Dr. Mikhael’s article on bispecific antibodies and contact the IMF InfoLine with your myeloma-related questions and concerns. Phone lines are open 9 a.m. to 4 p.m. (Pacific) Monday through Thursday, and 9 a.m. to 2 p.m. on Friday at 1.800.452.CURE in the U.S. and Canada and 1.818.487.7455 worldwide. To submit your query electronically, email [email protected]

(This article was published in the 2023 Fall Edition of the IMF's quarterly publication, Myeloma Today. Read the full publication here.)


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