Written by: Jeremiah Moore, PharmD
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Selinexor (Xpovio®) is a novel medication for patients with relapsed, refractory multiple myeloma. This PQI will provide background on the novel mechanism of action and discuss effective practices to maximize the use of selinexor therapy.

Background:

Selinexor is an oral, selective inhibitor of nuclear export (SINE) that blocks exportin 1 (XPO1). XPO1 is overexpressed in a number of cancers, including multiple myeloma, leading to enhanced transportation of tumor suppressor proteins and correlates with poor survival.

Selinexor is indicated in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody. Selinexor provides a novel therapy for a heavily pretreated patient population for which little to no previous options existed.

The phase 2 STORM trial investigated the combination of twice weekly selinexor and dexamethasone. Overall response rate was 26 % (95% CI 19 – 35) in a heavily pretreated patient population with a median (range) of 7 (3-18) prior treatment regimens.

PQI Process:

Upon receiving a new prescription for Selinexor:

  • Confirm appropriate dosing and schedule
  • Confirm receipt of dexamethasone and prophylactic anti-emetic for moderate to high emetogenicity
  • Consider prophylactic treatment with a 5-HT3 antagonist and/or other anti-nausea 30 minutes prior to administration
  • Ensure appropriate monitoring with a CBC, CMP, and body weight at baseline, then at least weekly for 8 weeks, then at least monthly thereafter
  • Monitor patients closely for side effects including:
    • Cytopenia (thrombocytopenia, anemia, neutropenia)
    • GI intolerance (Nausea, vomiting, diarrhea)
    • Fatigue
    • Weight loss
    • Hyponatremia
  • Educate patients on side effects and report adverse effects to prescriber

Dosing:

  • Selinexor 80 mg (4 x 20 mg tablets) by mouth twice weekly on days 1 and 3 until disease progression or unacceptable toxicity.
  • Dexamethasone 20 mg by mouth twice weekly on days 1 and 3 until disease progression or unacceptable toxicity.

Supportive Care/Adverse Effect Management

               Dose Reduction Steps for Adverse Reactions

Selinexor starting dose1st Reduction2nd Reduction3rd Reduction 

 

 

Discontinue

80 mg

Days 1 and 3 of each week

 

(160 mg total per week)

100 mg ONCE

Weekly

80 mg

ONCE

Weekly

60 mg

ONCE

Weekly

53% of patients had a reduction in dose, and 65.3% had a dose interrupted3

  • Gastrointestinal
    • Dose reduction and/or Drug holiday
    • Addition of olanzapine or NK1R antagonist for Nausea and Vomiting
    • Addition of loperamide for diarrhea
  • Hyponatremia
    • Interrupt when Sodium level ≤ 130 mmol/L
    • Oral and IV fluids and/or salt tablets
  • Weight Loss
    • Interrupt when weight loss between 10% to ≤ 20%
    • Consider Nutritionist consult and supplements such as Boost®, Ensure®
    • Consider addition of low dose olanzapine and/or megesterol acetate

Patient Centered Activities:

  • Provide Oncology Chemotherapy Education (OCE) sheet
  • Consider providing Xpovio (Selinexor) patient starter kit
  • Ensure patient knows dosing schedule including dexamethasone and prophylactic anti-nausea medications
  • Ensure patient knows to swallow the tablet whole with water. The tablet should not be broken, chewed, crushed, or divided
  • Ensure patient knows that blood tests and body weight will be monitored closely
  • Ensure patient knows the importance of maintaining adequate fluid and caloric intake throughout treatment

References:

  1. Vogl DT, Dingli D, Cornell RF, et al. Selective inhibition of nuclear export with oral selinexor for treatment of relapsed or refractory multiple myeloma. Journal of Clinical Oncology. 2018; 36: 859-866.
  2. Chen C, Siegel D, Gutierrez M, et al. Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and waldenstrom macroglobulinemia. Blood. 2018; 131(8): 855-963.
  3. Xpovio (selinexor) [package insert]. Newton, MA: Karyopharm Therapeutics Inc; 2019.
  4. Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. New England Journal of Medicine. 2019; 381:727-738.
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