Talquetamab: Drug information

(For additional information see "Talquetamab: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

ALERT: US Boxed Warning

Cytokine release syndrome:

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

Neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome:

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

Risk Evaluation and Mitigation Strategy:

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

Brand Names: US

Talvey

Pharmacologic Category

Antineoplastic Agent, Anti-CD3;
Antineoplastic Agent, Anti-GPRC5D;
Antineoplastic Agent, Bispecific T Cell Engager;
Antineoplastic Agent, Monoclonal Antibody

Dosing: Adult

Dosage guidance:

Safety: Due to the risk of cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS), patients should be hospitalized for 48 hours after all doses within the talquetamab step-up dosing schedule. Premedicate with a corticosteroid (IV or oral dexamethasone 16 mg or equivalent), a histamine H₁ antagonist (IV or oral diphenhydramine 50 mg or equivalent), and antipyretics (IV or oral acetaminophen 650 to 1,000 mg or equivalent) 1 to 3 hours prior to all doses within the talquetamab step-up dosing schedule to reduce the risk and severity of CRS. Premedication may be necessary prior to subsequent doses in patients who repeat doses within the talquetamab step-up dosing schedule (following a dose delay), or who experienced CRS following the prior talquetamab dose.

Clinical considerations : Administer prophylactic antimicrobials according to local guidelines.

Multiple myeloma, relapsed or refractory

Multiple myeloma, relapsed or refractory:

Note: Dose is based on actual body weight.

**Recommended Talquetamab Dosing Schedule^a**
Dosing schedule	Day	Dose
^a Continue treatment until disease progression or unacceptable toxicity (Chari 2022; Schinke 2023; manufacturer's labeling).
^b Dose may be administered 2 to 4 days after previous dose and, if necessary, up to 7 days after the previous dose to allow for resolution of adverse reactions.
^c Maintain ≥6 days between weekly doses and ≥12 days between biweekly (every 2 weeks) doses.
^d Dose may be administered between 2 to 7 days after step-up dose 3.
Weekly talquetamab SUBQ dosing schedule
Step-up dosing schedule	Day 1	Step-up dose 1	SUBQ: 0.01 mg/kg once
	Day 4^b	Step-up dose 2	SUBQ: 0.06 mg/kg once
	Day 7^b	First treatment dose	SUBQ: 0.4 mg/kg once
Weekly treatment dosing schedule	1 week after first treatment dose and weekly thereafter^c	Subsequent treatment doses	SUBQ: 0.4 mg/kg once weekly
Biweekly (every 2 weeks) talquetamab SUBQ dosing schedule
Step-up dosing schedule	Day 1	Step-up dose 1	SUBQ: 0.01 mg/kg once
	Day 4^b	Step-up dose 2	SUBQ: 0.06 mg/kg once
	Day 7^b	Step-up dose 3	SUBQ: 0.4 mg/kg once
	Day 10^d	First treatment dose	SUBQ: 0.8 mg/kg once
Biweekly (every 2 weeks) dosing schedule	2 weeks after the first treatment dose and every 2 weeks thereafter^c	Subsequent treatment doses	SUBQ: 0.8 mg/kg once every 2 weeks

**Recommendations for Restarting Talquetamab^a After Dose Delay**
Last talquetamab dose administered	Duration of delay from the last talquetamab dose administered	Action^b
^a Patients should be hospitalized for 48 hours after all doses within the talquetamab step-up dosing schedule.
^b Administer premedication prior to restarting talquetamab and monitor accordingly.
Weekly and biweekly (every 2 weeks) talquetamab dosing schedule
SUBQ: 0.01 mg/kg (step-up dose 1)	>7 days	Restart talquetamab step-up dosing schedule at step-up dose 1 (0.01 mg/kg).
SUBQ: 0.06 mg/kg (step-up dose 2)	8 to 28 days	Repeat talquetamab step-up dose 2 (0.06 mg/kg) and resume the step-up dosing schedule.
SUBQ: 0.06 mg/kg (step-up dose 2)	>28 days	Restart talquetamab step-up dosing schedule at step-up dose 1 (0.01 mg/kg).
Weekly talquetamab dosing schedule
SUBQ: 0.4 mg/kg (treatment dose)	8 to 28 days	Continue talquetamab weekly dosing schedule at treatment dose (0.4 mg/kg once weekly).
	29 to 56 days	Restart talquetamab step-up dosing schedule at step-up dose 2 (0.06 mg/kg).
	>56 days	Consider permanent discontinuation. If resuming therapy, restart talquetamab step-up dosing schedule at step-up dose 1 (0.01 mg/kg).
Biweekly (every 2 weeks) talquetamab dosing schedule
SUBQ: 0.4 mg/kg (step-up dose 3)	8 to 28 days	Repeat talquetamab step-up dose 3 (0.4 mg/kg) and resume the step-up dosing schedule.
	29 to 56 days	Restart talquetamab step-up dosing schedule at step-up dose 2 (0.06 mg/kg).
	>56 days	Consider permanent discontinuation. If resuming therapy, restart talquetamab step-up dosing schedule at step-up dose 1 (0.01 mg/kg).
SUBQ: 0.8 mg/kg (treatment dose)	15 to 28 days	Continue talquetamab weekly dosing schedule at treatment dose (0.8 mg/kg once every 2 weeks).
	29 to 56 days	Restart talquetamab step-up dosing schedule at step-up dose 3 (0.4 mg/kg).
	>56 days	Consider permanent discontinuation. If resuming therapy, restart talquetamab step-up dosing schedule at step-up dose 1 (0.01 mg/kg).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Note: Kidney function estimated using the Cockcroft-Gault formula.

CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant difference in talquetamab pharmacokinetics were observed based on CrCl 30 to 89 mL/minute.

CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's labeling (effects on talquetamab pharmacokinetics are unknown).

Dosing: Hepatic Impairment: Adult

Mild (total bilirubin ≤ ULN with AST > ULN or total bilirubin >1 to 1.5 times ULN with any AST) or moderate (total bilirubin >1.5 to <3 times ULN with any AST) impairment: There are no dosage adjustments provided in the manufacturer's labeling; however, no clinically significant difference in talquetamab pharmacokinetics was observed based on mild or moderate hepatic impairment.

Severe impairment (total bilirubin >3 times ULN with any AST): There are no dosage adjustments provided in the manufacturer's labeling (effects on talquetamab pharmacokinetics are unknown).

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m²: Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m² (Ref). Note: According to the prescribing information, the dose is based on actual body weight.

Dosing: Adjustment for Toxicity: Adult

Talquetamab dose delays may be necessary to manage toxicities. Refer to “Dosing: Adult” for recommendations on restarting talquetamab after dose delays.

Cytokine release syndrome: If cytokine release syndrome (CRS) is suspected, interrupt talquetamab until resolved; manage according to the table below and per clinical practice guidelines. Supportive therapy for CRS may include intensive care for severe or life-threatening CRS. Consider laboratory testing to monitor for disseminated intravascular coagulation, hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function. Evaluate and treat other causes of fever, hypoxia, and hypotension.

**Talquetamab-Related Cytokine Release Syndrome Management**
CRS grade^a	Symptoms	Actions
^a Based on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for CRS.
^b Fever may be masked by antipyretics or anticytokine therapy.
^c Tocilizumab may be considered in the management persistent grade 2, severe (grade 3), or life-threatening (grade 4) CRS associated with bi-specific T-cell engaging (BiTE) therapy (EMN [Ludwig 2023]; Lee 2014; Maude 2014); tocilizumab and/or corticosteroids were used (in the talquetamab clinical trial) to manage CRS in some patients (Chari 2022).
^d CRS = cytokine release syndrome; CPAP = continuous positive airway pressure; BiPAP = bilevel positive airway pressure.
Grade 1	Temperature ≥38°C (100.4°F)^battributed to CRS.	Withhold talquetamab until CRS resolves. Administer premedication prior to the next talquetamab dose.
Grade 2	Temperature ≥38°C (100.4°F)^b attributed to CRS, with hypotension responsive to fluids and not requiring vasopressors and/or oxygen requirement of low-flow nasal cannula (≤6 L/minute) or blow-by.	Withhold talquetamab until CRS resolves. Administer premedication prior to the next talquetamab dose. Patients should be hospitalized for 48 hours following the next talquetamab dose.
Grade 3	Temperature ≥38°C (100.4°F)^b attributed to CRS, with hypotension requiring one vasopressor with or without vasopressin and/or oxygen requirement of high-flow nasal cannula (>6 L/minute), face mask, nonrebreather mask, or Venturi mask.	Duration <48 hours: Withhold talquetamab until CRS resolves. Provide supportive therapy^c as clinically necessary (may include intensive care). Administer premedication prior to the next talquetamab dose. Patients should be hospitalized for 48 hours following the next talquetamab dose.
Grade 3		Recurrent grade 3 CRS or duration ≥48 hours: Permanently discontinue talquetamab and provide supportive care^c as clinically necessary (may include intensive care).
Grade 4	Temperature ≥38°C (100.4°F)^b attributed to CRS, with hypotension requiring multiple vasopressors (excluding vasopressin) and/or oxygen requirement of positive pressure (eg, CPAP, BiPAP, intubation, and mechanical ventilation).^d	Permanently discontinue talquetamab and provide supportive care^c as clinically necessary (may include intensive care).

Neurologic toxicity: Interrupt talquetamab at the first sign of neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS), and consider neurology evaluation. Rule out other causes of neurologic signs/symptoms. Supportive therapy may include intensive care for severe or life-threatening neurologic toxicities. Manage according to the table below and per clinical practice guidelines.

**Talquetamab-Related Neurologic Toxicity Management**
Adverse reaction	Severity	Actions
^aBased on American Society for Transplantation and Cellular Therapy (ASTCT) 2019 grading for ICANS.
^bManagement if determined by the most severe event (not attributable to any other cause).
^cIf patient is arousable and able to perform immune effector cell–associated encephalopathy (ICE) assessment: • Orientation (oriented to year, month, city, hospital = 4 points) • Naming (name 3 objects, eg, point to clock, pen, button = 3 points) • Following commands (eg, “show me 2 fingers” or “close your eyes and stick out your tongue” = 1 point) • Writing (ability to write a standard sentence = 1 point) • Attention (count backwards from 100 by 10 = 1 point) If unarousable and unable to perform ICE assessment (grade 4 ICANS = 0 points)
^d Not attributable to any other cause.
Neurologic toxicity (excluding ICANS)	Grade 1	Withhold talquetamab until neurologic toxicities/symptoms resolve or stabilize.
	Grade 2 or grade 3 (first occurrence)	Withhold talquetamab until neurologic toxicities/symptoms improve to ≤ grade 1. Provide supportive therapy as clinically appropriate.
	Recurrent grade 3 or grade 4	Permanently discontinue talquetamab. Provide supportive care as clinically appropriate (may include intensive care).
Recommendations for management of talquetamab-related ICANS
ICANS grade^a	Presenting symptoms^b	Actions
Grade 1	ICE score 7 to 9^c, or depressed level of consciousness^d(awakens spontaneously)	Withhold talquetamab until ICANS resolves. Monitor neurologic symptoms and consider consultation with neurologist/other specialists for further evaluation and management (eg, consider initiating seizure prophylaxis with nonsedating, antiseizure medication).
Grade 2	ICE score 3 to 6^c, or depressed level of consciousness^d (awakens to voice)	Withhold talquetamab until ICANS resolves. Administer dexamethasone (or equivalent) 10 mg IV every 6 hours; continue dexamethasone until resolution to ≤ grade 1, then taper. Monitor neurologic symptoms and consider consultation with neurologist/other specialists for further evaluation and management (eg, consider initiating seizure prophylaxis with nonsedating, antiseizure medication). Patients should be hospitalized for 48 hours following the next talquetamab dose.
Grade 3	ICE score 0 (but arousable) to 2^c, or depressed level of consciousness^d (awakens only to tactile stimulus), or seizures^d (either any clinical seizure, focal or generalized, that resolves rapidly, or nonconvulsive seizures on EEG that resolve with intervention), or raised intracranial pressure (focal/local edema on neuroimaging^d)	First occurrence of grade 3 ICANS: Manage as per grade 2 ICANS. Provide supportive therapy as clinically appropriate (may include intensive care).
Grade 3		Recurrent grade 3 ICANS: Permanently discontinue talquetamab. Manage as per grade 2 ICANS. Provide supportive therapy as clinically appropriate (may include intensive care).
Grade 4	ICE score 0^c, or depressed level of consciousness^d (either unarousable or requires vigorous/repetitive tactile stimuli to arouse, or stupor or coma), or seizures^d (either life-threatening prolonged seizure >5 minutes, or repetitive clinical or electrical seizures without return to baseline in between), or motor findings^d (deep focal motor weakness such as hemiparesis or paraparesis), or raised intracranial pressure/cerebral edema^d, with signs/symptoms including diffuse cerebral edema on neuroimaging, or decerebrate or decorticate posturing, or cranial nerve VI palsy, or papilledema, or Cushing triad	Permanently discontinue talquetamab. Manage as per grade 2 ICANS. Alternatively, instead of dexamethasone, consider methylprednisolone 1,000 mg IV daily and continue methylprednisolone 1,000 mg IV daily for ≥2 days. Provide supportive therapy as clinically appropriate (may include intensive care).

Other adverse reactions:

**Recommended Talquetamab Dosage Modifications for Other Adverse Reactions**
Adverse reaction	Severity	Actions
^a For grade 3 or 4 infection, if talquetamab is held for >28 days, restart step-up dosing when infection resolves to ≤ grade 1.
Dermatologic toxicity	Any	Consider early intervention and treatment.
Dermatologic toxicity	Grade 3 to 4	Withhold talquetamab until dermatologic toxicity improves to ≤ grade 1.
Hematologic toxicity	ANC <500/mm³	Withhold talquetamab until ANC is ≥500/mm³.
	Febrile neutropenia	Withhold talquetamab until ANC is ≥1,000/mm³ and fever resolves.
	Hemoglobin <8 g/dL	Withhold talquetamab until hemoglobin is ≥8 g/dL.
	Platelets <25,000/mm³ or platelets 25,000 to 50,000/mm³ with bleeding	Withhold talquetamab until platelets are ≥25,000/mm³ and no evidence of bleeding.
Infections	All grades	Withhold talquetamab for active infection during the step-up dosing schedule.
	Grade 3^a	Withhold subsequent talquetamab treatment doses until infection improves to ≤ grade 1 with 28 days.
	Grade 4^a	Consider permanent discontinuation of talquetamab. If not permanently discontinued, withhold subsequent treatment doses until infection improves to ≤ grade 1.
Oral toxicity/weight loss	Any	Further evaluate clinically significant weight loss.
	Grade 1 to 2	Provide supportive care (including nutritionist consultation) and continue talquetamab treatment dosing. Consider withholding talquetamab if not responsive to supportive care.
	Grade 3	Withhold talquetamab until oral toxicity/weight loss improves to ≤ grade 1. Provide supportive care (including nutritionist consultation).
	Grade 4	Permanently discontinue talquetamab. Provide supportive care (including nutritionist consultation).
Other nonhematologic adverse reactions	Grade 3	Withhold talquetamab until adverse reaction improves to ≤ grade 1.
Other nonhematologic adverse reactions	Grade 4	Consider permanent discontinuation of talquetamab. If not permanently discontinued, withhold subsequent treatment doses until adverse reaction improves to ≤ grade 1.

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported in adults.

>10%:

Cardiovascular: Edema (14%), hypotension (21%), tachycardia (11%)

Dermatologic: Dermatologic disorder (41%; including desquamation, palmar-plantar erythrodysesthesia, palmoplantar keratoderma, skin discoloration, and skin fissures), nail disease (50%; including koilonychia, nail bed changes, nail cuticle fissure, nail discoloration, nail dystrophy, nail hypertrophy, nail pitting, nail ridging, onychoclasis, onycholysis, and onychomadesis), pruritus (19%), skin rash (38%), xeroderma (30%; including dry eye)

Endocrine & metabolic: Decreased serum albumin (66%), decreased serum phosphate (44%), decreased serum potassium (31%), decreased serum sodium (31%), weight loss (35% to 62%)

Gastrointestinal: Constipation (16%), decreased appetite (19%), diarrhea (21%; grades 3/4: <1%), dysgeusia (49% to 70%; including ageusia [18%] and taste disorder), dysphagia (23%), mouth disease (12%; including oral disorder, oral dysesthesia, oral mucosal exfoliation, oral toxicity, and oropharyngeal pain), nausea (18%), stomatitis (18%; grades 3/4: 1%), xerostomia (34%)

Hematologic & oncologic: Decreased hemoglobin (67%; grades 3/4: 30%), decreased neutrophils (64%; grades 3/4: 35%), decreased platelet count (62%; grades 3/4: 22%), decreased white blood cell count (73%; grades 3/4: 35%), lymphocytopenia (90%; grades 3/4: 80%)

Hepatic: Increased gamma-glutamyl transferase (38%), increased serum alanine aminotransferase (33%), increased serum alkaline phosphatase (49%), increased serum aspartate aminotransferase (31%)

Hypersensitivity: Cytokine release syndrome (76%)

Infection: Infection (including bacterial infection [≤19%], fungal infection [10%], sepsis [≤8%], severe infection [16%], viral infection [<10%])

Local: Injection-site reaction (13%)

Nervous system: Chills (19%), fatigue (37%), headache (20% to 21%), neuropathy (14%; including dysesthesia, hyperesthesia, hypoesthesia, neuralgia, peripheral neuropathy, paresthesia, peripheral sensory neuropathy, polyneuropathy, sciatica and vestibular neuronitis), neurotoxicity (55%; including encephalopathy [15%], immune effector cell-associated neurotoxicity syndrome [ICANS]: 9%), pain (18%)

Neuromuscular & skeletal: Musculoskeletal pain (43%)

Respiratory: Cough (17%), dyspnea (11%), upper respiratory tract infection (22%)

Miscellaneous: Fever (83%)

1% to 10%:

Nervous system: Motor dysfunction (10%; including abnormal gait, amyotrophy, dysarthria, dysgraphia, dysmetria, muscle spasms, myasthenia, voice disorder)

Respiratory: Hypoxia (10%)

Contraindications

There are no contraindications listed in the manufacturer's labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Cytokine release syndrome: Cytokine release syndrome (CRS), including fatal or life-threatening reactions, may occur with talquetamab therapy; recurrent CRS has also been reported in approximately one-third of patients. Most patients experienced CRS during the step-up doses or with the initial 2 treatment doses. A small percentage of patients experienced CRS with subsequent talquetamab doses. The median time to onset of CRS was 27 hours (range: up to 167 hours) after the most recent dose and the median duration was 17 hours (range: up to 622 hours). Clinical signs/symptoms of CRS include (but are not limited to) fever, hypotension, chills, hypoxia, headache, and tachycardia. Life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, kidney and/or hepatic failure, and disseminated intravascular coagulation.

• Dermatologic toxicity: Talquetamab may cause serious skin reactions, such as erythema and rash (including maculopapular and erythematous rash). In clinical trials, dermatologic toxicity occurred in ~60% of patients, with most reactions being grade 1 to 2. The median time to onset of dermatologic toxicity was 25 days (range: 1 to 630 days) and the median time to improvement to ≤ grade 1 was 33 days.

• Hematologic toxicity: Talquetamab may cause cytopenias, including grades 3 or 4 neutropenia and thrombocytopenia. The median time to onset of grades 3 or 4 neutropenia was 22 days (range: 1 to 312 days) and the median time to improvement to ≤ grade 2 was 8 days (range: 1 to 79 days). The median time to onset of grades 3 or 4 thrombocytopenia was 12 days (range: 2 to 183 days) and the median time to improvement to ≤ grade 2 was 10 days (range: 1 to 64 days).

• Hepatotoxicity: Hepatotoxicity may occur with talquetamab. Elevated AST and ALT occurred in approximately one-third of patients, with a small percentage of grade 3 or 4 elevations; total bilirubin elevations (including grade 3 or 4 events) were also reported. Liver enzyme elevation may occur with or without concurrent CRS.

• Infection: Talquetamab may cause severe, life-threatening, or fatal infections. Serious infections (including bacterial infections, sepsis, and COVID-19) occurred in 16% of patients, with a similar percentage of grade 3 or 4 infections; fatal infections were reported in some patients.

• Neurologic toxicity: Talquetamab may cause serious or life-threatening neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS); some cases may be fatal. In a clinical trial, neurologic toxicity occurred in >50% of patients, with grade 3 or 4 events occurring in some patients. The most common neurologic events were headache, encephalopathy, sensory neuropathy, and motor dysfunction. ICANS was observed in ~10% of patients, including recurrent events in some; most patients experienced ICANS within the step-up dosing schedule and with the first treatment dose. The median time to onset of ICANS was 2.5 days (range: 1 to 16 days) after the most recent treatment dose with a median duration of 2 days (range: 1 to 22 days). ICANS may occur with or without the presence of CRS. Clinical signs/symptoms of ICANS may include (but are not limited to) confused state, depressed level of consciousness, disorientation, somnolence, lethargy, and slowed thinking and processing of information (bradyphrenia). Patients are at risk of depressed level of consciousness; advise patients to not drive or operate heavy machinery during and for 48 hours after completion of the step-up dosing schedule and with new onset of any neurologic toxicity symptoms until resolution.

• Oral toxicity and weight loss: Oral toxicities, including dysgeusia, dry mouth, dysphagia, and stomatitis, have occurred with talquetamab. Oral toxicities occurred in 80% of patients, with a small percentage of events being grade 3. The median time to onset of oral toxicity was 15 days (range: 1 to 634 days) and median time to resolution to baseline was 43 days (range: 1 to 530 days); two-thirds of patients did not have resolution of oral toxicity to baseline. Weight loss may also occur with talquetamab; weight loss may occur with or without the presence of oral toxicity. In a clinical trial, nearly two-thirds of patients experienced weight loss, including grade 2 to 3 events (≥10% weight loss from baseline). The median time to onset of ≥ grade 2 weight loss was 67 days (range: 6 to 407 days) and median time to resolution was 50 days (range: 1 to 403 days); over half of patients did not have resolution of weight loss.

Special populations:

• Older adults: In a clinical trial, there was a higher rate of fatal adverse reactions in patients ≥75 years of age when compared to patients <75 years of age.

Other warnings/precautions:

• REMS program: Talquetamab is available only through a restricted program under a REMS called the TECVAYLI and TALVEY Risk Evaluation and Mitigation Strategy (REMS) Program. Further information is available at www.TEC-TALREMS.com or 1-855-810-8064.

Product Availability

Talvey: FDA approved August 2023; availability anticipated in 2023.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Subcutaneous [preservative free]:

Talvey: Talquetamab-tgvs 40 mg/mL (1 mL); Talquetamab-tgvs 3 mg/1.5 mL (2 mg/mL) (1.5 mL) [contains edetate (edta) disodium]

Generic Equivalent Available: US

Pricing: US

Solution (Talvey Subcutaneous)

3 mg/1.5 mL (per mL): $621.60

40 mg/mL (per mL): $12,432.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

SUBQ: For SUBQ administration only. If refrigerated, allow solution to come to room temperature prior to administration. Administer SUBQ into the abdomen (preferred injection site); may be administered at other sites (eg, thigh). Doses requiring >2 mL total volume should be equally divided into multiple syringes. If multiple injection sites are required, they should be at least 2 cm apart. Do not inject into tattoos, scars, or areas where the skin is red, bruised, tender, hard, or not intact.

Administer in a facility with adequate medical personnel and appropriate equipment to manage severe adverse reactions.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Talvey: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761342s000lbl.pdf#page=30

Use: Labeled Indications

Multiple myeloma, relapsed or refractory: Treatment of relapsed or refractory multiple myeloma in adults who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Medication Safety Issues

Sound-alike/look-alike issues:

Talquetamab may be confused with tafasitamab, teclistamab.

Talvey may be confused with Tecvayli.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices includes among its list of drug classes that have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Talquetamab may increase the serum concentration of CYP Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Rozanolixizumab: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Verify pregnancy status prior to treatment initiation.

Patients who could become pregnant should use effective contraception during therapy and for 3 months after the last dose of talquetamab.

Pregnancy Considerations

Animal reproduction studies have not been conducted. Based on the mechanism of action, in utero exposure to talquetamab may cause fetal harm.

Talquetamab is a humanized bispecific antibody (IgG₄). Human IgG crosses the placenta. Fetal exposure is dependent upon the IgG subclass, maternal serum concentrations, placental integrity, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis and the highest during the third trimester (Clements 2020; Palmeira 2012; Pentsuk 2009).

Breastfeeding Considerations

It is not known if talquetamab is present in breast milk.

Talquetamab is a humanized bispecific antibody (IgG₄). Human IgG is present in breast milk; concentrations are dependent upon IgG subclass and postpartum age (Anderson 2021).

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 3 months after the last dose of talquetamab.

Monitoring Parameters

Monitor blood counts, liver enzymes, and bilirubin at baseline and during therapy as clinically indicated. Verify pregnancy status prior to treatment initiation (in patients who could become pregnant).

Due to the risk for cytokine release syndrome (CRS) and neurologic toxicity, patients should be hospitalized for 48 hours after administration of talquetamab step-up doses including the first treatment dose. Monitor for CRS (signs/symptoms may include fever, hypotension, chills, hypoxia, headache, and sinus tachycardia) and signs/symptoms of neurologic toxicity. Consider laboratory testing to monitor for disseminated intravascular coagulation, hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function.

Monitor for skin toxicity (including rash progression); monitor for signs/symptoms of infection prior to and during treatment; monitor for signs/symptoms of oral toxicity; monitor weight regularly during therapy.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Talquetamab is a bispecific T-cell engaging therapy that binds to the CD3 receptor expressed on the surface of T-cells and G protein-coupled receptor class C group 5 member D (GPRC5D). GPRC5D is primarily expressed on malignant and nonmalignant plasma cells and hard keratinized healthy tissue (eg, epithelial tissue of skin and tongue), with low expression in other normal human tissue. Upon binding to both GPRC5D and CD3, lysis of malignant plasma cells occurs via T-cell recruitment and activation, leading to the release of proinflammatory cytokines (Chari 2022).

Pharmacokinetics (Adult Data Unless Noted)

Distribution: V_d: 10.1 L.

Metabolism: Metabolized into small peptides via catabolic pathways.

Bioavailability: SUBQ: 59%.

Half-life elimination: 8.4 days after the first treatment dose; 12.2 days at 16 weeks after the first treatment dose.

Time to peak:

0.4 mg/kg weekly treatment dose: 3.7 days (0.9 to 7 days) after the first treatment dose; 2.5 days (0.9 to 5.9 days) after the seventeenth treatment dose.

0.8 mg/kg biweekly (every 2 weeks) treatment dose: 3.4 days (0.8 to 14 days) after the first treatment dose; 3.6 days (1 to 7.7 days) after the ninth treatment dose.

Excretion: Clearance: Decreases over time; 0.9 L/day at 16 weeks after the first treatment dose.

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Body weight: The talquetamab V_d and clearance increase with increasing body weight (40 kg to 143 kg).

Anderson PO. Monoclonal antibodies during breastfeeding. Breastfeed Med. 2021;16(8):591-593. doi:10.1089/bfm.2021.0110 [PubMed 33956488]
Chari A, Minnema MC, Berdeja JG, et al. Talquetamab, a T-cell-redirecting GPRC5D bispecific antibody for multiple myeloma. N Engl J Med. 2022;387(24):2232-2244. doi:10.1056/NEJMoa2204591 [PubMed 36507686]
Clements T, Rice TF, Vamvakas G, et al. Update on transplacental transfer of IgG subclasses: impact of maternal and fetal factors. Front Immunol. 2020;11:1920. doi:10.3389/fimmu.2020.01920 [PubMed 33013843]
Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol. 2021;39(18):2037-2048. doi:10.1200/JCO.21.00471 [PubMed 33939491]
Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
Lee DW, Gardner R, Porter DL, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124(2):188-195. doi:10.1182/blood-2014-05-552729 [PubMed 24876563]
Ludwig H, Terpos E, van de Donk N, et al. Prevention and management of adverse events during treatment with bispecific antibodies and CAR T cells in multiple myeloma: a consensus report of the European Myeloma Network. Lancet Oncol. 2023;24(6):e255-e269. doi:10.1016/S1470-2045(23)00159-6 [PubMed 37269857]
Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J. 2014;20(2):119-122. doi:10.1097/PPO.0000000000000035 [PubMed 24667956]
Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646. doi:10.1155/2012/985646 [PubMed 22235228]
Pentsuk N, van der Laan JW. An interspecies comparison of placental antibody transfer: new insights into developmental toxicity testing of monoclonal antibodies. Birth Defects Res B Dev Reprod Toxicol. 2009;86(4):328-344. doi:10.1002/bdrb.20201 [PubMed 19626656]
Schinke C, Touzeau C, Minnema MC, et al. Pivotal phase 2 MonumentTAL-1 results of talquetamab (tal), a GPRC5DxCD3 bispecific antibody (BsAb), for relapsed/refractory multiple myeloma (RRMM). J Clin Oncol. 2023;41(16 suppl):S8036. doi:10.1200/JCO.2023.41.16_suppl.8036
Talvey (talquetamab) [prescribing information]. Horsham, PA: Janssen Biotech, Inc; August 2023.

Topic 142419 Version 15.0

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Talquetamab: Drug information