15

November

Selinexor Patient Management in Relapsed or Refractory Multiple Myeloma

Written by: Jeremiah Moore, PharmD
Download Here

This PQI will provide background on the novel medication Selinexor (Xpovio®) and discuss effective practices to maximize the use of this therapy in relapsed or refractory multiple myeloma.

Background:

Selinexor is an oral, selective inhibitor of nuclear export (SINE) that blocks exportin 1 (XPO1). 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. Selinexor is also indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.

The STORM trial investigated the combination of twice weekly selinexor and dexamethasone in Relapsed or Refractory Multiple Myeloma. Overall response rate was 21% (95% CI 19 – 35) in a heavily pretreated patient population with a median (range) of 8 (4-18) prior treatment regimens.

PQI Process:

Upon receiving a new prescription for Selinexor:

  • Confirm appropriate dosing and schedule for Relapsed or Refractory Multiple Myeloma
    • Confirm receipt of dexamethasone and prophylactic anti-emetic for moderate to high emetogenicity o See Chemotherapy-Induced Nausea and Vomiting PQI https://www.ncoda.org/chemotherapy-induced-nausea-and-vomiting/
    • 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. Consider monitoring more frequently during the first three months of treatment.
    • 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 for Multiple Myeloma is recommended at 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 dose for Multiple Myeloma

1st Reduction

2nd Reduction

3rd Reduction

4th Reduction

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

Discontinue

49% of patients had a reduction in dose, and 61% had a dose interrupted

  •  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; 2020.
  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.
Victoria

Victoria has blogged 1090 posts

View all PQI