Usual Adult Dose for Follicular Lymphoma

Cycle one
Day 1: IV infusion of 1mg once over at least 4 hours
Day 8: IV infusion of 2mg once over at least 4 hours
Day 15: IV infusion of 60mg once over at least 4 hours

Cycle two
Day 1: IV infusion of 60mg once over at least 2 hours if infusions from Cycle 1 were well-tolerated

Cycle three onwards
Day 1: IV infusion of 30mg once over at least 2 hours if infusions from Cycle 1 were well-tolerated

Duration of therapy:
Treatment duration based on complete or partial response unless unacceptable toxicity or disease progression occurs:

• Patients with complete response: 8 cycles
• Patients with partial response: 17 cycles total (8 initial cycles + 9 more cycles)

Comments:

• Premedicate before each dose during Cycle 1 and Cycle 2; ensure adequate hydration prior to administering this drug.
• Do not use an in-line filter to administer this drug.
• Patients who achieved a partial response or stable disease after 8 cycles of treatment with this drug are eligible for an additional 9 cycles of treatment (17 cycles total) unless they experience unacceptable toxicity or disease progression.
• Refer to the manufacturer's prescribing information for premedication and recommendations for restarting therapy with this drug after a dose delay.

Use: For the treatment of adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

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

Cytokine Release Syndrome:
Grade 1

• Withhold treatment and institute appropriate therapy.
• If symptoms resolve, restart the infusion at the same rate.
• Ensure CRS symptoms are resolved for at least 72 hours prior to the next dose.
• Administer premedication prior to the next dose of this drug and monitor the patient more frequently.

Grade 2

• Withhold treatment and institute appropriate therapy.
• If symptoms resolve, restart the infusion at a 50% rate.
• Ensure CRS symptoms are resolved for at least 72 hours prior to the next dose.
• Administer premedication prior to the next dose of this drug and consider infusing the next dose at a 50% rate.
• During the next dose, monitor more frequently and consider hospitalization.

Recurrent Grade 2 CRS:

• Manage according to Grade 3 recommendations.

Grade 3

• Withhold treatment with this drug and institute appropriate therapy, which may include intensive care.
• Ensure CRS symptoms are resolved for at least 72 hours prior to the next dose.
• Administer premedication prior to next dose of this drug and infuse the next dose at 50% rate.
• Consider hospitalization for the next dose of this drug.

Recurrent Grade 3 CRS:

• Permanently stop treatment with this drug.
• Manage CRS according to current practice guidelines and institute appropriate therapy which may include intensive care.

Grade 4

• Permanently stop treatment with this drug.
• Manage CRS according to current practice guidelines and institute appropriate therapy which may include intensive care.

Neurologic Toxicity, including Cell-Associated Neurotoxicity Syndrome (ICANS):

• Withhold treatment with this drug at the first sign of neurologic toxicity, including ICANS and consider neurology evaluation.
• Rule out other causes of neurologic symptoms.
• Institute supportive therapy, which may include intensive care.

Grade 2

• Withhold treatment with this drug until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 72 hours.
• Institute supportive therapy.
• If ICANS, manage per current practice guidelines.

Grade 3

• Withhold treatment with this drug until neurologic toxicity symptoms improve to Grade 1 or baseline for at least 72 hours.
• Institute supportive therapy which may include intensive care and consider neurology evaluation.
• If ICANS, manage per current practice guidelines.
• If recurrence, permanently stop treatment with this drug.

Grade 4

• Permanently stop treatment with this drug.
• Institute supportive therapy which may include intensive care and consider neurology evaluation.
• If ICANS, manage per current practice guidelines.

Infections:
Grades 1 to 4:

• Withhold treatment with this drug in patients with active infection until the infection resolves.
• Permanently stop treatment with this drug for Grade 4 infections.

Neutropenia
Absolute neutrophil count less than 0.5 × 10(9)/L:

• Withhold treatment with this drug until absolute neutrophil count is 0.5 × 10(9)/L or higher.

Other Adverse Reactions
Grade 3 or higher:
Withhold treatment with this drug until the toxicity resolves to Grade 1 or baseline.

Precautions

US BOXED WARNING:

• Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving this drug.

Recommendations:

• Initiate treatment with the step-up dosing schedule to reduce the risk of CRS.
• Withhold treatment with this drug until CRS resolves or permanently discontinue depending on severity.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Patients should be well-hydrated before administering this drug.
• Do not use an in-line filter to administer this drug.
• Drip chamber filters can be used to administer this drug.
• Ensure adequate medical support and resource availability to manage severe reactions such as cytokine release syndrome and neurologic toxicity.
• Before administering the infusion solution, ensure it has reached room temperature.
• Do not mix this drug with, or administer it through the same infusion line as, other medicinal products.

Storage requirements:

• Store refrigerated at 2C to 8C (36F to 46F) in the original carton to protect from light.
• Do not freeze or shake.
• Diluted solution can be stored refrigerated at 2C to 8C (36F to 46F) for up to 24 hours or at ambient temperature 9C to 30C (48F to 86F) for up to 16 hours.

Preparation techniques:
See manufacturer product information for completion preparation instructions.

General:

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

Monitoring:
Nervous system: Neurologic toxicity
Infections: Opportunistic infections
Hematologic: Complete blood cell counts
Oncologic: Tumor flare

Patient advice:

• Read the FDA-approved patient labeling (Medication Guide).
• Seek immediate medical attention if signs or symptoms of CRS occur at any time.
• Seek immediate medical attention if signs or symptoms of neurologic toxicity occur.
• Avoid driving or operating machinery if you feel drowsy or dizzy.
• There is a possibility of a tumor flare reaction with the use of this drug; notify healthcare provider if any sign or symptom associated with a tumor flare is seen.

This drug may cause fetal harm when administered to a pregnant woman; notify health care provider if you are pregnant or become pregnant during therapy.

• Use effective contraception during treatment with this drug and for 3 months after the last dose.
• Do not breastfeed during treatment with this drug and for 3 months after the last dose.