Developed under the direction and sponsorship of Johnson & Johnson

Dr Noa Biran, Susan Kumka and Maribel Pereiras are paid consultants for Johnson & Johnson and must present information in accordance with US Food & Drug Administration (FDA) requirements applicable to Johnson & Johnson.

Multiple myeloma remains incurable, and most patients will inevitably relapse and cycle through multiple lines of therapy.² The treatment landscape of relapsed or refractory multiple myeloma is still evolving, and new treatments have been showing powerful efficacy in patients. However, as patients exhaust multiple lines of therapy with each relapse,² different treatment options and regimens are sorely needed for this chronic and incurable disease.

In recent years, a different approach to treating a variety of can- cer types including lung cancer has emerged, called bispecific antibody therapy. This therapy has been proven to work for relapsed or refractory multiple myeloma patients, offering another option for patients who have been on several prior lines of therapy.³ Bispecific antibodies harness the body’s immune system to attack myeloma cells.⁴

Until recently, the only bispecific antibodies approved for mul- tiple myeloma targeted BCMA (B-cell maturation antigen). Talvey® (talquetamab-tgvs) is the first and only bispecific antibody to target GPRC5D (G protein-coupled receptor class C group 5 member D) and CD3 (cluster of differentiation 3), which is prom- inently expressed on malignant multiple myeloma cells, nonmalignant plasma cells, and healthy tissues such as epithelial cells and in keratinized tissues of the skin and tongue.⁵ This is an important treatment option for patients who have not previously been treated with T-cell redirecting therapies [eg, chimeric anti- gen receptor (CAR) T-cell therapy or bispecific antibody therapy] or if they have had prior exposure to BCMA-targeted treatment options (eg, CAR T-cell therapy).

Talvey was granted accelerated approval by the FDA in August 2023 for the treatment of adult patients with relapsed or refrac- tory multiple myeloma who have received at least 4 prior lines of therapy including a proteasome inhibitor (PI), an immuno- modulatory agent, and an anti-CD38 monoclonal antibody.⁵ The accelerated approval was based on results of the phase 1/2 MonumenTAL-1 study, which established powerful efficacy in 219 patients, with the overall response rate in the every-2-weeks cohort at 73.6%, the weekly cohort at 73%, and the cohort of patients exposed to prior T-cell redirection therapy at 72%.⁵ This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefits in confirmatory trial(s).⁵

The single-arm, open-label, multicenter, phase 1/2 MonumenTAL-1 study looked at both patients naïve to and those exposed to T-cell redirection therapy, such as CAR T-cell therapy or other bispecific antibodies.⁵ Patients naïve to T-cell redirection therapy were randomized to receive Talvey every 2 weeks or weekly, whereas patients exposed to T-cell redirection therapy received Talvey once weekly.⁵ Patients in the MonumenTAL-1 study had received ≥3 prior systemic therapies including a PI, an immunomodulatory agent, and an anti-CD38 monoclonal anti- body. The primary endpoint of the study was overall response rate. The secondary endpoints included duration of response and time of response.⁵

Results from the phase 1/2 MonumenTAL-1 study showed powerful efficacy with an overall response rate of more than 70% across 3 cohorts (ie, patients naïve to T-cell redirection therapy on every-2-week and weekly regimens, as well as patients exposed to prior T-cell redirection therapy).⁵ Responses were durable: the median duration of response has not been reached in patients receiving an every-2-week dose; for patients receiving a weekly dose, median duration of response was 9.5 months.⁵

Extended follow-up analysis of the MonumenTAL-1 study was presented in 2024 and represented a median follow-up of about 20 to 30 months, depending on the cohort.⁶ It should be highlighted that these data are not included in the Prescribing Information for Talvey.⁵ It included 190 patients with no prior exposure to T-cell redirection therapy: 90 patients on every-2- week dosing regimen and 100 patients on the weekly dosing reg- imen.⁷ The increase in the number of patients compared to those reported in the Prescribing Information is due to the additional patients enrolled in the clinical study and subsequently included in the longer-term follow-up.⁷ For the every-2-week dosing of Talvey, patients at the median follow-up of 23 months showed a medium duration of response of 17.9 months.⁷ Patients given weekly dosing had a median follow-up of over 29 months and a median duration of response of 10.2 months^.7

Talvey should only be administered by a health care professional with appropriate medical support.⁵ Talvey comes with a Boxed Warning regarding the risk of cytokine release syndrome (CRS) and neurotoxicity, including immune effector cell-associated neu- rotoxicity syndrome (ICANS).

There is a Boxed Warning for TALVEY® regarding the risk of cytokine release syndrome and neurotoxicity, including ICANS.

Warnings & Precautions:

• Oral Toxicity and Weight Loss
• Infections
• Cytopenias
• Skin Toxicity
• Hepatotoxicity
• Embryo-Fetal Toxicity

Adverse Reactions:

The most common adverse reactions are pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache. Grade 3 or 4 laboratory abnormalities are lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemo- globin decreased. Please see the full Important Safety Information in this article.

The safety profile of Talvey shows the discontinuation rate due to an adverse event is 9%.⁵ Notably, infection is a general concern for patients with relapsed or refractory multiple myeloma who are heavily pretreated and immunocompromised. Talvey Grade 3 or 4 infections occurred in 17% of patients.⁵ Patients should consult with their health care provider to manage any side effects with supportive care and/or dosing adjustments.

Talvey is available through a restricted program called a Risk Evaluation and Mitigation Strategy, or REMS.5 Prescribing health care providers, pharmacies, and health care settings must become REMS-certified to provide this treatment option to patients.⁵

Importance of Education

With the emergence of bispecific antibody therapies in multiple myeloma, community cancer centers are establishing clinical protocols to support patients to receive care in their community. To gain insights into implementing Talvey in a community setting, Oncology Issues spoke with the myeloma treatment team at John Theurer Cancer Center of Hackensack Meridian Health in Hackensack, New Jersey. The team includes Noa Biran, MD, a hematologist/oncologist in the multiple myeloma division and an associate professor of medicine at Hackensack University School of Medicine; Susan Kumka, MSN, APN, RN-BC, a nurse practitioner specializing in multiple myeloma and hematologic malignancies; and Maribel Pereiras, PharmD, BCPS, BCOP, an oncology pharmacist at Hackensack University Medical Center. Their collective expertise highlights best practices for administering Talvey and emphasizes both patient and staff education.

Given Talvey’s mechanism of action and its specific side effect profile, comprehensive education for both health care providers and patients is essential, according to Dr Biran. Providers need to be well versed in administration protocols, potential adverse events, and management strategies to ensure patient safety and treatment efficacy. This education includes understanding the unique attributes of this therapy such as the step-up dosing phase, recognition and management of side effects, and the knowledge of when to involve multidisciplinary team members like nutritionists and dermatologists.

Providing comprehensive education to providers on the identification and management of specific side effects enables the multidisciplinary team members to empower patients to take informed steps in their care and provide the proper support that patients need throughout their treatment journey. Additionally, staff training on these management strategies ensures that any issues can be addressed promptly and appropriately. Education needs to extend beyond the primary care treatment team in both the inpatient and outpatient settings and include staff members who may encounter the patient at any point while on treatment. These staff include patient care technicians who are aware of vital signs that require immediate attention and emergency department (ED) providers who may encounter patients experiencing severe adverse events from treatment that require immediate medical attention.

Expert Insight

Managing Adverse Events

Patients receiving these treatments may experience rapid- onset complications that require quick recognition and intervention to prevent serious outcomes. Familiarity with the signs and symptoms of cytokine release syndrome and neurotoxicity, including immune effector cell-associated neurotoxicity syndrome, allows emergency staff to triage and manage these patients appropriately.

Extending this education to those outside the primary treat- ment clinic also ensures that, even when patients present with unrelated issues, they receive “personalized care that may include supportive treatments or prompt communication with the patient’s oncology team for further management,” Pereiras continued.

Expert Insight

Supportive Services and Adverse Events

We take a proactive approach to manage expected toxicities with nutritional counseling, patient education, [and] weight monitoring; [encourage consumption of] small, frequent meals; and still [advocate] for treatment. [Based on the severity of symptoms,] we monitor our patients for signs and symptoms of these adverse events and consider withholding or discontinuing Talvey in some instances, but our goal is to always achieve the best response and help our patients get the optimal benefit of the therapy. In our practice, we have developed measures to help patients manage these symptoms and avoid discontinuation.

Dr Biran’s approach to treating patients with relapsed or refrac- tory multiple myeloma involves onboarding her entire team early in the treatment process to establish clear protocols and ensure that all team members are properly educated on every aspect of Talvey administration. She prioritizes forming a multidisciplinary team that includes pharmacists, dietitians, nurse coordinators, and nurse navigators from the beginning to enhance care coordination and patient support. Dr Biran highlights the importance of involving nutritionists early on to monitor patients’ weight and nutritional health, which tend to be part of the challenges associated with adverse events that may occur with treatment.

For patients, education is equally important to prepare them for what may occur during treatment, including understanding potential side effects and recommendations to mitigate them. “When patients and care partners are well-informed about pre- ventive measures and management techniques, it could reduce the need for specialist interventions, thereby streamlining care and improving patient outcomes,” Dr Biran said. This education not only improves patient comfort and adherence to treatment but also optimizes the use of health care resources. Dr Biran and her multidisciplinary team emphasized the need to set clear expectations with patients before starting treatment with Talvey, noting that side effects may persist even after treatment is stopped.

Expert Insight

Patient education is paramount, as it could prevent discontinuation due to side effects if patients are adequately informed before treatment is initiated.

In interviews with Oncology Issues, Kumka emphasized the importance of educating patients and their care partners about the dosing and treatment before going into the hospital. This education includes outlining the step-up dosing schedule and administration logistics, providing guidance on potential side effects, and advising patients to read the Medication Guide for Talvey.

Kumka stated that her team of nurses provides a review of “side effects that patients will probably experience and those that they will possibly experience.” She shared that up-front education focuses mostly on “what our patients typically [share with us] about the side effects they experience, from those [who] have been on the drug for a long time.”

Kumka emphasized the value of sharing practical tips learned from previous patients, particularly regarding food choices early in treatment. “We tell [patients] up front that smoothies will be your friend at the beginning, because patients may have difficulty swallowing due to decreased mucus production, so dry foods should be avoided. Keeping up protein intake, drinking frequently, and using mouth rinses are really important.”

From the moment admission orders are given to when the drug is first administered and throughout the treatment calendar, the care team is continually reinforcing patient expectations. Kumka added that education must continue even after discharge from the hospital following the step-up dosing phase, stating, “Once discharged and seen in the outpatient setting, we also speak with the patient and continue reiterating the information and explanation of the treatment calendar moving forward.”

Expert Insight

The Crucial Role of Clinical Oncology Pharmacists

In terms of patient education, [the clinical oncology pharmacist] explains the treatment process, expected outcomes, and ways to manage side effects, empowering patients to engage in their care. Additionally, [pharmacists] communicate with and educate health care staff about Talvey, sharing insights on best practices for administration and monitoring, which enhances the overall treatment strategy and patient safety.

Pereiras emphasized that early education on the full treatment dose is crucial to ensure that patients are vigilant for any poten- tial late-onset side effects. “Patients should understand the importance of regular follow-up appointments and [laboratory] tests to monitor their response to therapy and manage any emerging issues proactively,” advised Pereiras. “We try to ensure patients maintain their quality of life throughout their treatment to the extent possible.”

Patient Case Study

Dr Biran highlighted the potential for successful Talvey administration in a community setting through strong referral networks, proper care coordination, and support. To illus- trate this potential, she shared a compelling case study of an ideal candidate for Talvey treatment in this environment.

The patient was diagnosed with multiple myeloma and had rapid progression and minimal response to 4 prior lines of therapy including a PI, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Despite undergoing a stem cell transplant, the patient did not achieve a durable response, and other therapies also failed to show signifi- cant efficacy. Due to the rapid progression of the disease, the patient was not a candidate for CAR T-cell therapy, which requires time to harvest T-cells. Immediate treatment was necessary, so Talvey was a suitable option.

The patient had been transferred to Hackensack Meridian Health for Talvey treatment initiation and experienced grade 2 cytokine release syndrome, which was managed with supportive care medications. After being stabilized, the patient transitioned back to their REMS-certified local oncologist to continue receiving Talvey. Remarkably, the patient achieved complete remission. It is important to note that every patient’s experience is unique and not representative of all patients. Monthly telemedicine visits were conducted to monitor tumor markers and signs of toxicity. The patient experienced dysgeusia with weight loss and had the appropriate adjustment to their dosing schedule. After 6 to 7 months, the dysgeusia improved, allowing the patient to resume the every-2-week dosing, which will continue until either disease progression or the development of unacceptable toxicity.

This patient case study highlights that dose adjustments to mitigate toxicities should be a focus of outpatient treat- ment. Patients should remain on every-2-week or weekly dosing to ensure optimal efficacy and confirm that the patient is tolerating the therapy well.

Expert Insight

Our goal is to always achieve the best response and help our patients get the optimal benefit of the treatment, which is why our practice has developed measures to help patients manage their symptoms and avoid discontinuation.

Starting Patients on Talvey

Talvey has flexible dosing with 2 dosing schedule options: an every-2-week dose injection of 0.8 mg/kg or a weekly dose injection of 0.4 mg/kg following the step-up dosing schedule.5 Injections are subcutaneous and must be administered by a health care provider.5 Physicians should decide with their patients which treatment schedule is best, depending upon the individual patient’s needs.5 Both dosing options require an initial step-up dosing schedule in which they receive the first 2 or 3 doses of Talvey at a smaller dose and slowly increase up to the full treatment dose.5 Patients are hospitalized for 48 hours after administration of each step-up dose, which allows them to be monitored for any potential serious or life-threatening side effects, including cytokine release syndrome and neurologic problems such as immune effector cell-associated neurotoxicity syndrome.⁵

The management of side effects related to Talvey such as oral and dermatologic toxicities5 requires thorough patient education and a multidisciplinary approach to monitoring and support. Dr Biran reiterated the importance of proactively discussing these side effects with patients and how the side effects could be manageable for most patients.

Dr Biran shared that in her practice treating patients with Talvey, “We’ve learned how to manage these toxicities where patients can go on to continue their therapy, and, often, the toxicities can be potentially mitigated and some patients can often tolerate the expected side effects, especially when their disease is under control.”

Transitioning Care from the Academic to the Community Setting

Care transitions for patients receiving Talvey involve meticulous planning and coordination to ensure continuity and quality of care. The process begins with the initiation of step-up dosing at the academic center. This transition involves coordinating with local oncologists, health care settings, and the pharmacy, ensuring that all are REMS-certified to administer Talvey.

Communication between academic and community providers is critical. Dr Biran notes that on the day of admission for step-up dosing, the academic center should consider connecting the local oncologist with a Johnson & Johnson Talvey field representative to ensure that the community clinic and/or pharmacy are preparing for the eventual transition, which includes being certified in the Talvey REMS program

Expert Insight

Patient Transition and REMS Certification

We call their referring oncologist the day that the patient gets admitted, so the referring oncologist can start to become REMS-certified and set up their own clinic for administration of outpatient Talvey. The patient prefers to get their treatment locally, if at all possible, especially if they are receiving an every-2-week dosing regimen in the beginning. The referring physician often will touch base with their own Johnson & Johnson representative, and then we’re happy to make that connection with their team in order to get REMS-certified. We then get the patient’s pharmacy on board, get their nutritionist on board, and educate their nurses and their team in terms of how to get acquainted with the therapy and manage side effects.

This proactive, collaborative approach ensures that all necessary protocols and support systems are in place before the patient moves back to their community oncologist’s care. Regular telemedicine visits and continuous monitoring of tumor markers and for signs of toxicity help to maintain high standards of care, even in resource-constrained settings.⁸ At her academic center, Dr Biran does telehealth consults with local oncologists and their patients; these include monthly telemedicine visits when patients are on the full treatment dose.

Pereiras explained that the transition to a community care setting should align with the reduced need for frequent medication adjustments, typically when patients enter the full treatment dose phase of every-2-week dosing. Continuous education and support from oncology clinical educators are vital to manage ongoing treatment and potential side effects.

Pereiras stated that community pharmacists “should try to leverage team collaboration by fostering strong communication with the care team to ensure coordinated care and quick response to any complications. Streamlining processes with protocols or guidelines can help optimize workflow and maintain consistency.” An integrated care approach supported via telemedicine and regular monitoring allows patients to receive high-quality care closer to home, improving their overall treatment experience.⁸

A key resource available for clinical staff, patients, and care partners are oncology clinical educators employed by Johnson & Johnson. These oncology clinical educators include advanced practice providers (APPs) and registered nurses (RNs) who play a pivotal role in educating about Talvey at community settings and helping to bridge the gap between complex clinical protocols and practical, patient-centered care. These professionals work closely with the clinical team to ensure that all health care providers are well informed about Talvey’s mechanism of action, administration protocols, and potential side effects.⁹ This comprehensive understanding is vital for the safe and effective use of Talvey, particularly in settings where access to specialized care may be limited.

Oncology clinical educators can also help to educate patients on what to expect during treatment with Talvey. Through educational sessions, materials, and ongoing support, oncology clinical educators can also help provide support to promote adherence to the treatment.⁸ This collaborative approach enhances the quality of care and can help improve patient outcomes, ensuring that health care providers and patients alike are well prepared to navigate the complexities of treatment with Talvey in community care settings.

More information on oncology clinical educators can be found at https://www.talveyhcp.com/get-in-touch/

Advice for Community Programs

Before administration of Talvey occurs, providers should become educated about this bispecific antibody treatment option and the opportunity it can provide patients with relapsed or refractory multiple myeloma. This education includes talking to colleagues who are already prescribing Talvey.

To successfully administer Talvey in community settings, it is essential to establish a strong framework that prioritizes patient safety and helps support treatment efficacy. This framework includes participation from every member of the multidisciplinary team to create a comprehensive treatment care plan and provide the proper education for patients and care part- ners. Leveraging educational resources and establishing both proactive and reactive processes can help build confidence and support the successful adoption of Talvey into community programs, even in resource-constrained settings.

Staff should prioritize education and stay up to date on treatment protocols, dosing guidelines, and proper management of potential side effects.

Expert Insight

Patient Navigation and Community Outreach

[The care team should] identify and collaborate with local support services and organizations that can assist patients with logistical challenges such as transportation or financial assistance.

In addition to forming and coordinating care across the multidis- ciplinary team, the community program needs to create a clear process for admitting patients to an inpatient unit for higher-level care before treating the first patient. This process should be com- municated to all team members, ensuring that patient care tech- nicians, ED staff, and local hospital personnel are well versed in the drug’s administration protocols and potential side effects.

Kumka stressed the involvement of multidisciplinary team mem- bers, including infectious disease providers and social workers. “We have our infectious disease specialists [who] are very familiar with the drugs, because when patients are in the hospital with fevers, we do usually have them consult directly.” Social workers are especially essential, Kumka continued, “as patients enter later stages of care.”

Starting with a small number of patients can help build confidence and familiarity with Talvey’s treatment protocol. Dr Biran suggests trialing the drug with 1 or 2 patients initially before expanding the program. This approach allows the team to refine their processes and address any challenges in a controlled manner. Both community and academic treatment teams should identify the optimal time for transitioning care.

Dr Biran suggested, “The best point at which a patient can transition from an academic to community setting is upon completion of cycle 1. So, we can start cycle 2 in the community. We are happy to transition the patient, so the first dose administered in the outpatient setting is a full treatment dose.” Establishing communication channels between academic centers and community providers is vital for smooth transitions of care.

Kumka highlighted the importance of designating a nurse liaison who is specifically trained in managing side effects for multiple myeloma patients. At the John Theurer Cancer Center, the team gets “an inpatient APP involved in the process. She does more teaching when [patients] are admitted and initiates the process of getting a nutritionist involved, which is very important from the very beginning.” Additionally, utilizing APPs to manage complica- tions, especially when the treating oncologist is unavailable, can help to reduce urgent care or ED visits.

Establishing clinical protocols to support patients to receive care in their community may help to achieve health equity and better outcomes for patients. By following these recommendations, community settings can effectively integrate Talvey into their treatment protocols, optimize patient outcomes, and improve the overall quality of care.

Community settings administering Talvey can successfully manage step-up dosing hospitalization and provide comprehensive treat- ment care, enabling patients to receive therapy closer to home. With strong coordination and communication between care sites, teams can optimize Talvey use and improve patient outcomes even in resource-limited environments. Many tools and educational materials are available to support the care team, patients, and care partners throughout this transition. These resources help to ensure that patients can continue benefiting from Talvey for as long as needed. Leveraging all available guidance and support can not only simplify the transition of care but also help commu- nity sites to start their own patients on Talvey so that a broader population of patients have the opportunity to receive treatment for relapsed or refractory multiple myeloma.

Molly Kisiel, MSN, FNP-BC, is director of clinical content at the Association of Cancer Care Centers in Rockville, Maryland.

Key Takeaways

• Establish a comprehensive framework for patient safety and treatment efficacy.
• Engage a multidisciplinary team including pharmacists, dietitians, nurse coordinators, and nurse navigators.
• Provide comprehensive education for all care team members including patient care technicians and emergency department staff.
• Emphasize patient education about potential side effects and treatment expectations.
• New prescribers and health care settings should start with a small number of patients to build confidence and refine processes.
• Ensure clear communication channels between aca- demic centers and community providers beginning with a strong peer-to-peer referral network.
• Implement both proactive (nutrition, education) and reactive (urgent care, emergency department) protocols.
• For more information, visit TalveyHCP.com.
  

TALVEY® Important Safety Information

INDICATION AND USAGE

TALVEY® (talquetamab-tgvs) is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a protea- some inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

This indication is approved under accelerated approval based on response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY, including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TALVEY®. Initiate TALVEY® treatment with step-up dosing to reduce the risk of CRS. Withhold TALVEY® until CRS resolves or permanently discontinue based on severity.

Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), and serious and life-threaten- ing or fatal reactions, can occur with TALVEY®. Monitor patients for signs and symptoms of neurologic toxicity including ICANS during treatment and treat promptly. Withhold or permanently discontinue TALVEY® based on severity.

Because of the risk of CRS and neurologic toxicity, including ICANS, TALVEY® is available only through a restricted pro- gram called the TECVAYLI® and TALVEY® Risk Evaluation and Mitigation Strategy (REMS).

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS

Cytokine Release Syndrome (CRS): TALVEY® can cause cytokine release syndrome, including life-threatening or fatal reactions. In the clinical trial, CRS occurred in 76% of patients who received

TALVEY® at the recommended dosages, with Grade 1 CRS occur- ring 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 (N=153). 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 (range: 0.1 to 167) hours from the last dose, and the median duration was 17 (range: 0 to 622) hours. Clinical signs and symptoms of CRS include but are not limited to pyrexia, hypotension, chills, hypoxia, headache, and tachycardia. Potentially life-threatening complications of CRS may include car- diac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).

Initiate therapy with step-up dosing and administer pre-treatment medications (corticosteroids, antihistamine, and antipyretics) prior to each dose of TALVEY® in the step-up dosing schedule to reduce the risk of CRS. Monitor patients following administration accordingly. In patients who experience CRS, pre-treatment medications should be administered prior to the next TALVEY® dose.

Counsel patients to seek medical attention should signs or symptoms of CRS occur. At the first sign of CRS, immediately evaluate patient for hospitalization and institute treatment with supportive care based on severity, and consider further management per current practice guidelines. Withhold TALVEY® until CRS resolves or permanently discontinue based on severity.

Neurologic Toxicity including ICANS: TALVEY® can cause serious, life-threatening neurologic toxicity or fatal neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). In the clinical trial, neurologic toxicity, including ICANS, occurred in 55% of patients who received 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 where ICANS was collected and who received the recommended dosages. 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%) (N=156) or the biweekly dosing schedule (3.7%) (N=109). The median time to onset of ICANS was 2.5 (range: 1 to 16) days after the most recent dose with a median duration of 2 (range: 1 to 22) days. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disori- entation, somnolence, lethargy, and bradyphrenia.

Monitor patients for signs and symptoms of neurologic toxicity during treatment and treat promptly. At the first sign of neuro- logic toxicity, including ICANS, immediately evaluate the patient and provide supportive care based on severity. Withhold or permanently discontinue TALVEY® based on severity and consider further management per current practice guidelines [see Dosage and Administration (2.5)].

Due to the potential for neurologic toxicity, patients receiving TALVEY® are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during the step-up dosing schedule and for 48 hours after completion of the step-up dosing schedule, and in the event of new onset of any neurological symptoms, until symptoms resolve.

TECVAYLI® and TALVEY® REMS: TALVEY® is available only through a restricted program under a REMS, called the TECVAYLI® and TALVEY® REMS because of the risks of CRS and neurologic toxicity, including ICANS.

Further information about the TECVAYLI® and TALVEY® REMS program is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064.

Oral Toxicity and Weight Loss: TALVEY® can cause oral toxicities, including dysgeusia, dry mouth, dysphagia, and stomatitis. In the clinical trial, 80% of patients had oral toxicity, with Grade 3 occur- ring in 2.1% of patients who received the recommended dosages. The most frequent oral toxicities were dysgeusia (49%), dry mouth (34%), dysphagia (23%), and ageusia (18%). The median time to onset of oral toxicity was 15 (range: 1 to 634) days, and the median time to resolution to baseline was 43 (1 to 530) days. Oral toxicity did not resolve to baseline in 65% of patients.

TALVEY® can cause weight loss. In the clinical trial, 62% of patients experienced weight loss, regardless of having an oral toxicity, including 29% of patients with Grade 2 (10% or greater) weight loss and 2.7% of patients with Grade 3 (20% or greater) weight loss. The median time to onset of Grade 2 or higher weight loss was 67 (range: 6 to 407) days, and the median time to resolution was 50 (range: 1 to 403) days. Weight loss did not resolve in 57% of patients who reported weight loss.

Monitor patients for signs and symptoms of oral toxicity. Counsel patients to seek medical attention should signs or symptoms of oral toxicity occur and provide supportive care as per current clinical practice, including consultation with a nutritionist. Monitor weight regularly during therapy. Evaluate clinically significant weight loss further. Withhold TALVEY® or permanently discontinue based on severity.

Infections: TALVEY® can cause infections, including life-threatening or fatal infections. 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%), which included sepsis, and COVID-19 (2.7%).

Monitor patients for signs and symptoms of infection prior to and during treatment with TALVEY® and treat appropriately. Administer prophylactic antimicrobials according to local guidelines. Withhold or consider permanent discontinuation of TALVEY® as recommended based on severity.

Cytopenias: TALVEY® can cause cytopenias, including neutropenia and thrombocytopenia. In the clinical trial, 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 (range: 1 to 312) days, and the median time to resolution to Grade 2 or lower was 8 (range: 1 to 79) days. The median time to onset for Grade 3 or 4 thrombocy- topenia was 12 (range: 2 to 183) days, and the median time to resolution to Grade 2 or lower was 10 (range: 1 to 64) days. Monitor complete blood counts during treatment and withhold TALVEY® as recommended based on severity.

Skin Toxicity: TALVEY® can cause serious skin reactions, including rash, maculo-papular rash, erythema, and erythematous rash. In the clinical trial, skin reactions occurred in 62% of patients, with Grade 3 skin reactions in 0.3%. The median time to onset was 25 (range: 1 to 630) days. The median time to improvement to Grade 1 or less was 33 days.

Monitor for skin toxicity, including rash progression. Consider early intervention and treatment to manage skin toxicity. Withhold TALVEY® as recommended based on severity.

Hepatotoxicity: TALVEY® can cause hepatotoxicity. Elevated ALT occurred in 33% of patients, with Grade 3 or 4 ALT elevation occur- ring in 2.7%; elevated 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.

Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TALVEY® or consider permanent discontinuation of TALVEY® based on severity (see Dosage and Administration [2.5]).

Embryo-Fetal Toxicity: Based on its mechanism of action, TALVEY® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TALVEY® and for 3 months after the last dose.

Adverse Reactions: The most common adverse reactions (≥20%) are pyrexia, CRS, dysgeusia, nail disorder, musculoskeletal pain, skin disorder, rash, fatigue, weight decreased, dry mouth, xerosis, dysphagia, upper respiratory tract infection, diarrhea, hypotension, and headache.

The most common Grade 3 or 4 laboratory abnormalities (≥30%) are lymphocyte count decreased, neutrophil count decreased, white blood cell decreased, and hemoglobin decreased.

Please read full Prescribing Information, including Boxed WARNING, for TALVEY®.

cp-394174v5

ACKNOWLEDGMENTS

ACCC would like to extend gratitude to Dr Noa Biran, Susan Kumka, and Maribel Pereiras for their contributions to this article. Their expertise and dedication have been instrumental in advancing the understanding and implementation of Talvey for the treatment of relapsed or refractory multiple myeloma.

References

1. Myeloma Cancer stat facts. SEER. Accessed September 7, 2024. https://seer.cancer.gov/statfacts/html/mulmy.html
2. Bhatt P, Kloock C, Comenzo R. Relapsed/refractory multi- ple myeloma: a review of available therapies and clinical scenarios encountered in myeloma relapse. Curr Oncol. 2023;30(2):2322-2347. doi:10.3390/curroncol30020179
3. Sun Y, Yu X, Wang X, et al. Bispecific antibodies in cancer therapy: target selection and regulatory requirements. Acta Pharm Sin B. 2023;13(9):3583-3597. doi:10.1016/j. apsb.2023.05.023
4. Swan D, Murphy P, Glavey S, Quinn J. Bispecific antibod- ies in multiple myeloma: opportunities to enhance effi- cacy and improve safety. Cancers (Basel). 2023;15(6):1819. doi:10.3390/cancers15061819
5. TALVEY®. Prescribing information. Horsham, PA: Janssen Biotech, Inc.
6. Rasche L, Schinke C, Touzeau C, et al. Long-term efficacy and safety results from the phase 1/2 MonumenTAL-1 study of talquetamab, a GPRC5D×CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma. Poster presented at: 2024 European Hematology Association Hybrid Congress; June, 14, 2024; Madrid, Spain. Poster MM-492.
7. Data on file. Janssen Biotech, Inc.
8. Digital tools in cancer care: survey results. Association of Cancer Care Centers . 2023. Accessed September 5, 2024. https:// www.accc-cancer.org/home/learn/management-operations/ oncology-practice-transformation-and-integration-center/ digital-tools
9. TALVEY® (talquetamab-tgvs) HCP. Johnson & Johnson; 2024. Accessed September 11, 2024. https://www.talveyhcp.com/ get-in-touch/

ADDITIONAL RESOURCES

For Care Teams

TALVEY® Treatment Management Guide

TALVEY® Prior Authorization Checklist

TALVEY® Access & Reimbursement Guide

ACCC irAE Workup Guidelines

ACCC OI Article: Best Practices for Implementing Cancer Immunotherapies in the Community

ACCC Virtual Toxicity Teams

ACCC Care Coordination & Communication

For Patients and Care Partners

TALVEY® Patient Brochure

TALVEY® Doctor Discussion Guide

TALVEY® Patient Journey

REMS Wallet Card

TALVEY® Care Partner Brochure

TALVEY® Care Navigators and Financial Assistance

© Johnson & Johnson and its affiliates 2025 03/25 cp-483334v1