Usual Adult Dose for Multiple Myeloma

Step-up dose 1: 0.06 mg/kg subcutaneously on Day 1
Step-up dose 2: 0.3 mg/kg subcutaneously on Day 4
Maintenance dose: 1.5 mg/kg subcutaneously on Day 7 and weekly thereafter.

Duration of therapy: Until disease progression or unacceptable toxicity.

Comments:

• Initiate therapy with this drug in patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
• Injection volume should not exceed 2 mL; divide doses requiring more than 2 mL equally into multiple syringes.
• Do not combine vials of different concentrations to achieve the treatment dose.
• Consider initiating antiviral prophylaxis prior to initiating therapy with this drug to prevent herpes zoster reactivation.
• Administer pretreatment medications (corticosteroids, histamine-1 (H1) receptor antagonist, and antipyretics) 1 to 3 hours prior to each step-up dose which includes the first maintenance dose to reduce the risk of CRS and adverse reactions; monitor patients accordingly.
• Due to the risk of cytokine release syndrome (CRS) and neurologic toxicity, including ICANS, hospitalize patients for 48 hours after administration of all step-up doses including the first maintenance dose.
• Step-up dose 2 can be administered 2 to 4 days after step-up dose 1, and up to 7 days later to allow for resolution of adverse reactions.
• The first maintenance dose can be given 2 to 4 days after step-up dose 2 and up to 7 days later to allow for the resolution of adverse reactions.
• If step-up dose 2 gets delayed for more than 7 days after step-up dose 1, then restart the step-up dosing schedule at step-up dose 1 (0.06 mg/kg).
• If the first maintenance dose gets delayed for 8 to 28 days after step-up dose 2, then restart step-up dose 2 (0.3 mg/kg) and continue the step-up dosing schedule.
• If the first maintenance dose gets delayed for more than 28 days after step-up dose 2, then restart the step-up dosing schedule at step-up dose 1 (0.06 mg/kg).
• If any maintenance dose gets delayed for 8 days to 28 days, then continue the weekly dosing schedule at the maintenance dose (1.5 mg/kg).
• If any maintenance dose gets delayed for more than 28 days, then restart the step-up dosing schedule at step-up dose 1 (0.06 mg/kg).
• The use of this drug is approved under accelerated approval based on response rate.
• Refer to manufacturer prescribing information for recommended pretreatment medications.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Dosage reductions are not recommended.

DOSE MODIFICATIONS FOR ADVERSE REACTIONS:

Refer to manufacturer product information for full details on dose modification and management of adverse reactions .

Cytokine Release Syndrome (CRS):
If CRS is suspected, withhold the therapy and institute appropriate treatment.
Grade 1:

• Withhold doses until CRS resolves and administer pretreatment medications prior to the next dose.

• Withhold doses until CRS resolves, administer pretreatment medications prior to the next dose, and hospitalize the patient for 48 hours following the next dose.

• First Occurrence with Duration Less than 48 Hours: Withhold doses and institute appropriate treatment; administer pretreatment medications prior to the next dose; and hospitalize the patient for 48 hours following the next dose.
• Recurrent Grade 3 CRS lasting 48 hours or longer: Discontinue the drug permanently and begin appropriate therapy.

• Discontinue the drug permanently and institute appropriate therapy.

• Neurologic Toxicity:

• Withhold the doses until symptoms of neurologic toxicity resolve or stabilize.

• Withhold the doses until severity reduces to grade 1 or less and provide supportive therapy.

• Discontinue the drug permanently and institute appropriate therapy.

• Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS):

• Withhold the doses until ICANS resolves and consider consulting a neurologist.

• Withhold the doses until ICANS resolves; institute appropriate therapy; and hospitalize the patient for 48 hours following the next dose.

• At the first occurrence of Grade 3 ICANS, withhold the doses until ICANS resolves; institute appropriate therapy; and hospitalize the patient for 48 hours following the next dose.
• Recurrent Grade 3 ICANS: Discontinue the drug permanently and institute appropriate therapy.

• Discontinue the drug permanently and institute appropriate therapy.

• Other Adverse Reactions:

• Withhold the dose in patients with active infection during the step-up dosing schedule.

• Withhold subsequent doses until the severity is reduced to grade 1 or less.

• Permanently discontinue the drug; if not, withhold subsequent doses until the severity is reduced to grade 1 or less.

• Withhold the doses and institute appropriate treatment. Refer to the manufacturer prescribing information for more details.

• Withhold doses until severity reduces to grade 1 or less.

• Discontinue the drug permanently; if it cannot be discontinued permanently, withhold doses until the severity is reduced to grade 1 or less.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for teclistamab-cqyv. It includes a medication guide. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNING:
Cytokine Release Syndrome and Neurologic Toxicity, Including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS):

• This drug has the potential to cause life-threatening or fatal reactions, including cytokine release syndrome (CRS).
• Neurologic toxicity, including ICANS and serious and life-threatening reactions, occurred with the use of this drug.
• Due to the risk of CRS and neurologic toxicity, including ICANS, this drug is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TECVAYLI REMS.

• Initiate treatment per a step-up dosing schedule to reduce the risk of CRS.
• Withhold therapy with this drug to allow for resolution of CRS and neurologic toxicity or permanently discontinue based on severity.
• Monitor for signs or symptoms of neurologic toxicity, including ICANS, during the therapy.

Dialysis

Data not available

Other Comments

Administration advice:

• The healthcare provider administering this drug should be equipped to manage severe reactions, including CRS and ICANS.
• Inspect the drug product for the presence of particulate matter and discoloration prior to administration.
• Do not inject if the solution is discolored or if foreign particles are present.
• Do not dilute prior to administration.
• Inject the required volume of this drug into the subcutaneous tissue of the abdomen, which is the preferred injection site for this drug. Alternatively, it can also be injected into the subcutaneous tissue at other sites (e.g., the thigh).
• If multiple injections are required, this drug should be injected at least 2 cm apart.
• Do not inject into tattoos, scars, or areas where the skin is red, bruised, tender, hard, or not intact.
• Dispose of the unused drug or waste material in accordance with local requirements.

• Keep refrigerated at 2C to 8C (36F to 4F) in the original carton and protect from light.
• Do not freeze.
• Prepared dosing syringe(s): Store at 2C to 8C (36F to 46F) or at ambient temperature 15C to 30C (59F to 86F) for a maximum of 20 hours. Discard the syringe(s) after 20 hours if not used.

• Prepare and administer this drug under aseptic conditions.
• Remove the appropriate-strength drug vial from the refrigerator and equilibrate to an ambient temperature of 15C to 30C (59F to 86F) for at least 15 minutes. Do not warm it in any other way.
• Once equilibrated, gently swirl the vial for approximately 10 seconds to mix. Do not shake.
• Withdraw the required injection volume of drug from the vial(s) into an appropriately sized syringe using a transfer needle.
• Each injection volume should not exceed 2 mL; divide doses requiring more than 2 mL equally into multiple syringes.

• This drug is compatible with stainless steel injection needles and polypropylene or polycarbonate syringe material.

• Due to the risk of CRS and neurologic toxicity, including ICANS, hospitalize patients for 48 hours after administration of all doses within the step-up dosing schedule.

• Immediately contact your health care provider if you have signs or symptoms of CRS or neurologic toxicity.
• Refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after the completion of the step-up dosing schedule and until neurologic toxicity resolves.
• Carry the patient wallet card provided.
• Monitor for liver enzyme elevations and report if any symptoms indicative of liver toxicity, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice, occur.
• If signs and symptoms associated with systemic administration-related reactions, neutropenia, febrile neutropenia, and infection occur, inform your healthcare provider immediately and seek medical attention.
• This drug may cause local injection-site reactions; notify your healthcare provider if severe local injection-site reactions occur.
• Notify your doctor if you are pregnant or become pregnant during treatment.
• Use adequate methods of contraception during treatment and for 5 months after the last dose, as this drug has the potential to harm a fetus.
• Breastfeeding is not advised during use of this drug and for 5 months after the last dose.
• Read the US FDA-approved patient labeling (Medication Guide).

Frequently asked questions

• What is the mechanism of action for Tecvayli (teclistamab-cqyv)?