selinexor (Rx)

Multiple Myeloma

Indicated in combination with dexamethasone for adults with relapsed or refractory multiple myeloma (RRMM) 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

80 mg PO plus dexamethasone 20 mg PO on Days 1 and 3 of each week

Continue until disease progression or unacceptable toxicity

Diffuse Large B-Cell Lymphoma

Indicated for relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, in patients previously treated with at least 2 lines of systemic therapy

60 mg PO on Days 1 and 3 of each week

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Dosage reduction recommendations for adverse effects

• RRMM

  • Starting dose: 80 mg on Days 1 and 3 each week (160 mg/week)
  • First reduction: 100 mg once weekly
  • Second reduction: 80 mg once weekly
  • Third reduction: 60 mg once weekly
  • Fourth reduction: Permanently discontinue

• DLBCL

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

Thrombocytopenia (RRMM)

• Platelet count 25,000-75,000/mcL: Reduce by 1 dose level
• Platelet count 25,000-75,000/mcL with bleeding: Interrupt dosing; restart at 1 dose level lower after bleeding resolved
• Platelet count <25,000/mcL: Interrupt dosing; monitor until platelet count returns to ≥50,000/mcL, then restart at 1 dose level lower

Thrombocytopenia (DLBCL)

• Platelet count 50,000 to <75,000/mcL: Interrupt 1 dose; restart at the same dose level

• Platelet count 25,000 to <50,000/mcL without bleeding

  • First occurrence: Interrupt dose; monitor until platelet count returns to ≥50,000/mcL
  • Reduce by 1 dose level

• Platelet count 25,000 to <50,000/mcL with concurrent bleeding

  • Interrupt dose; monitor until platelet count returns to ≥50,000/mcL
  • Restart at 1 dose level lower, after bleeding has resolved
  • Administer platelet transfusions per clinical guidelines

• Platelet count <25,000/mcL

  • Interrupt dose; monitor until platelet count returns to ≥50,000/mcL
  • Restart at 1 dose level lower
  • Administer platelet transfusions per clinical guidelines

Neutropenia (RRMM)

• ANC 0.5-1 x 10⁹/L without fever: Reduce by 1 dose level
• ANC <0.5 x 10⁹/L or febrile neutropenia: Interrupt dosing; monitor until neutrophil count returns to ≥1 x 10⁹/L, then restart at 1 dose level lower

Neutropenia (DLBCL)

ANC 0.5 to <1 x 10^9/L without fever

• First occurrence: Interrupt dose; monitor until neutrophil counts return to ≥1 x 10⁹/L; restart at the same dose level
• Recurrence: Interrupt dose; monitor until neutrophil counts return to ≥1 x 10⁹/L; administer growth factors per clinical guidelines; restart at 1 dose level lower
• ANC <0.5 x 10⁹/L or febrile neutropenia: Interrupt dosing; monitor until neutrophil count returns to ≥1 x 10⁹/L; administer growth factors per clinical guidelines; restart at 1 dose level lower

Anemia

• Hemoglobin <8 g/dL: Reduce by 1 dose level; administer blood transfusion and/or other treatments per clinical guidelines
• Life-threatening consequences (urgent intervention indicated): Interrupt dosing; monitor until hemoglobin ≥8 g/dL, then restart at 1 dose level lower; administer blood transfusion and/or other treatments per clinical guidelines

Hyponatremia

• Serum sodium <130 mmol/L: Interrupt dosing and provide supportive care
• Monitor until sodium returns to ≥130 mmol/L
• Restart at 1 dose level lower

Fatigue

• Grade 2 lasting >7 days or Grade 3: Interrupt dosing
• Monitor until fatigue resolves to Grade 1 or baseline
• Restart at 1 dose level lower

Nausea & vomiting

• Grade 1 or 2

  • Grade 1 or 2 nausea (decrease oral intake without significant weight loss, dehydration, or malnutrition) OR
  • Grade 1 or 2 vomiting (≤5 episodes/day)
  • Maintain dose and initiate additional antinausea medications

• Grade ≥3

  • Grade 3 nausea (inadequate oral caloric or fluid intake) OR
  • Grade ≥3 vomiting (≥6 episodes/day)
  • Interrupt dosing; monitor until nausea/vomiting resolved to ≤Grade 2; initiate additional antinausea medications; restart at 1 dose level lower

Diarrhea

• Grade 2 (inrease of 4-6 stools/day over baseline): If 1st episode, maintain dose and institute supportive care
• Grade 2 (2nd and subsequent episodes): Reduce by 1 dose level; institute supportive care
• Grade ≥3 (increase ≥7 stools/day over baseline; hospitalization indicated): Interrupt dosing and institute supportive care; monitor until resolved to Grade ≤2; restart at 1 dose level lower

Weight loss and anorexia

• Weight loss of 10-20% or anorexia associated with significant weight loss or malnutrition
• Interrupt and institute supportive care
• Monitor until weight returns to >90% baseline
• Restart at 1 dose level lower

Other nonhematologic adverse effects

• Grade 3 or 4 (life-threatening)

  • Interrupt dosing
  • Monitor until resolved to Grade ≤2
  • Restart at 1 dose level lower

Renal impairment

• Mild-to-severe (CrCl 15-89 mL/min): No significant differences in pharmacokinetics observed
• ESRD (CrCl <15 mL/min) or hemodialysis: Effect on pharmacokinetics unknown

Hepatic impairment

• Mild: No significant differences in pharmacokinetics observed
• Moderate-to-severe: Effect on pharmacokinetics unknown

Dosing Considerations

Concomitant treatment

• Maintain adequate fluid and caloric intake throughout treatment
• Consider IV hydration for patients at risk of dehydration
• Provide prophylactic concomitant treatment with a 5–HT3 antagonist and/or other antinausea agents before and during treatment

Monitor parameters

• Monitor at baseline and as clinically indicated
• Monitor more frequently during the first 3 months of treatment
• Assess the need for dosage modifications for adverse reaction
• CBC with differential
• Standard blood chemistries
• Body weight
• Nutritional status
• Volume status

Safety and efficacy not established