Usual Adult Dose for Multiple Myeloma

IN COMBINATION WITH BORTEZOMIB AND DEXAMETHASONE (SVd):
100 mg orally once weekly on Day 1 of each week until disease progression or unacceptable toxicity in combination with bortezomib 1.3 mg/m2 subcutaneously once weekly on Day 1 of each week for 4 weeks followed by 1 week off; dexamethasone 20 mg orally twice weekly on Days 1 and 2 of each week

IN COMBINATION WITH DEXAMETHASONE:
80 mg orally on Day 1 and 3 of each week until disease progression or unacceptable toxicity in combination with dexamethasone 20 mg orally with each dose of selinexor on Days 1 and 3 of each week

Comments:

• For additional information regarding the administration of bortezomib and dexamethasone, refer to its prescribing information.
• Consider IV hydration for patients at risk of dehydration.
• Provide prophylactic concomitant treatment with a 5-HT3 antagonist and/or other anti-nausea agents prior to and during therapy.

• In combination with bortezomib and dexamethasone for patients with multiple myeloma who have received at least 1 prior therapy
• In combination with dexamethasone for patients with relapsed or refractory multiple myeloma who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody

Usual Adult Dose for Lymphoma

60 mg orally on Day 1 and 3 of each week until disease progression or unacceptable toxicity

Comments:

• Consider IV hydration for patients at risk of dehydration.
• Provide prophylactic concomitant treatment with a 5-HT3 antagonist and/or other anti-nausea agents prior to and during therapy.

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

DOSE REDUCTION FOR ADVERSE REACTIONS:
Multiple Myeloma in combination with bortezomib and dexamethasone (SVd):

• Starting dose: 100 mg once a week
• First reduction: 80 mg once a week
• Second reduction: 60 mg once a week
• Third reduction: 40 mg once a week
• Fourth reduction: Permanently discontinue therapy.

• Starting dose: 80 mg on Days 1 and 3 of each week (160 mg total per week)
• First reduction: 100 mg once a week
• Second reduction: 80 mg once a week
• Third reduction: 60 mg once a week
• Fourth reduction: Permanently discontinue therapy.

• Starting dose: 60 mg on Day 1 and 3 of each week (120 mg total per week)
• First reduction: 40 mg on Days 1 and 3 of each week (80 mg total per week)
• Second reduction: 60 mg once a week
• Third reduction: 40 mg once a week
• Fourth reduction: Permanently discontinue therapy.

• Platelet count 25,000 to less than 75,000/mcL: For any occurrence reduce the dose by 1 dose level.
• Platelet count 25,000 to less than 75,000/mcL with concurrent bleeding: For any occurrence interrupt therapy; restart at 1 dose level lower after bleeding has resolved; administer platelet transfusions per guidelines.
• Platelet count less than 25,000/mcL: For any occurrence interrupt therapy; monitor until platelet count returns to at least 50,000/mcL; restart at 1 dose level lower.

• Absolute neutrophil count 0.5 to 1 x 10(9)/L without fever: For any occurrence reduce the dose by 1 dose level.
• Absolute neutrophil count less than 0.5 x 10(9)/L OR febrile neutropenia: For any occurrence interrupt therapy; monitor until neutrophil count returns to 1 x 10(9)/L or higher; restart at 1 dose level lower.

• Hemoglobin less than 8 g/dL: For any occurrence reduce the dose by 1 dose level; administer blood transfusions per guidelines.
• Life-threatening consequences: For any occurrence interrupt therapy; monitor hemoglobin until levels return to 8 g/dL or higher; restart therapy at 1 dose level lower; administer blood transfusions per guidelines.

• Platelet count 50,000 to less than 75,000/mcL: For any occurrence interrupt one dose of this drug; restart this drug at the same dose level.
• Platelet count 25,000 to less than 50,000/mcL without bleeding: For the first occurrence, interrupt therapy; monitor until platelet count returns to at least 50,000/mcL; reduce by one dose level.
• Platelet count 25,000/mcL to less than 50,000/mcL with concurrent bleeding: For any occurrence interrupt therapy; monitor until platelet count returns to at least 50,000/mcL; restart at 1 dose level lower after bleeding resolves; administer platelet transfusions per guidelines.
• Platelet count less than 25,000/mcL: For any occurrence interrupt therapy; monitor until platelet count returns to at least 50,000/mcL; restart at 1 dose level lower; administer platelet transfusions per guidelines.

• Absolute neutrophil count 0.5 to less than 1 x 10(9)/L without fever: For the first occurrence interrupt therapy; monitor until neutrophil counts return to 1 x 10(9)/L or higher; restart at the same dose level. For a recurrence interrupt therapy; monitor until neutrophil counts return to 1 x 10(9) or higher; administer growth factors per guidelines; restart at one dose level lower.
• Absolute neutrophil count less than 0.5 x 10(9)/L OR febrile neutropenia: For any occurrence interrupt therapy; monitor until neutrophil count returns to 1 x 10(9)/L; restart at 1 dose level lower.

• Hemoglobin less than 8 g/dL: For any occurrence reduce the dose by 1 dose level; administer blood transfusions per guidelines.
• Life-threatening consequences: For any occurrence interrupt therapy; monitor hemoglobin until levels return to 8 g/dL or higher; restart therapy at 1 dose level lower; administer blood transfusions per guidelines.

• Grade 1 or 2 nausea (oral intake decreased without significant weight loss, dehydration, or malnutrition) OR Grade 1 or 2 vomiting (5 or fewer episodes per day): For any occurrence continue therapy and initiate additional anti-nausea medications.
• Grade 3 nausea (inadequate oral caloric or fluid intake) OR Grade 3 or higher vomiting (6 or more episodes per day): For any occurrence interrupt therapy; monitor until nausea or vomiting has resolved to Grade 2 or lower or baseline; initiate additional anti-nausea medications; restart therapy at 1 dose level lower.

• Grade 2 (increase of 4 to 6 stools per day over baseline): For first occurrence continue therapy and institute supportive care; for second and subsequent occurrences reduce dose by 1 dose level and institute supportive care.
• Grade 3 or higher (increase of 7 stools or more per day over baseline; hospitalization indicated): For any occurrence interrupt therapy and institute supportive care; monitor until diarrhea resolves to Grade 2 or lower; restart therapy at 1 dose level lower.

• Weight loss of 10% to less than 20% OR anorexia associated with significant weight loss or malnutrition: For any occurrence interrupt therapy and institute supportive care; monitor until weight returns to more than 90% of baseline weight; restart therapy at 1 dose level lower.

• Sodium level 130 mmol/L or less: For any occurrence interrupt therapy and provide supportive care; monitor until sodium levels return to 130 mmol/L or higher; restart therapy at 1 dose level lower.

• Grade 2 lasting longer than 7 days OR Grade 3: For any occurrence interrupt therapy; monitor until fatigue resolves to Grade 1 or baseline; restart therapy at 1 dose level lower.

• Grade 2 excluding cataract: For any occurrence perform ophthalmologic evaluation; interrupt therapy and provide supportive care; monitor until ocular symptoms resolve to Grade 1 or baseline; restart therapy at 1 dose level lower.
• Grade 3 or greater excluding cataract: For any occurrence permanently discontinue therapy; perform ophthalmologic evaluation.

• Grade 3 or 4 (life-threatening): For any occurrence interrupt therapy; monitor until resolved to Grade 2 or lower; restart therapy at 1 dose level lower.

Precautions

CONTRAINDICATIONS:

• None

Dialysis

Data not available

Other Comments

Administration advice:

• This drug should be taken at the same time each day.
• Swallow tablets whole with water; do not break, chew, crush, or divide the tablet.
• If a dose is missed or delayed, take the next dose at the next regularly scheduled time.
• If a patient vomits a dose, the patient should not repeat the dose and should take the next dose on the next regularly scheduled day.

• Store at or below 30C (86F).

• Monitor complete blood count (CBC) with differential, standard blood chemistries, body weight, nutritional status, and volume status at baseline and during therapy as indicated. Monitor more frequently during the first 3 months.

• Maintain adequate fluid and caloric intake throughout therapy.