Written by: Jeremiah Moore, PharmD, University of Rochester Medical Center
Description: This PQI will provide background on the novel medication selinexor for patients with multiple myeloma (MM) who have received at least one prior therapy, relapsed, refractory multiple myeloma (RR-MM), and relapsed, refractory diffuse large b-cell lymphoma (RR-DLBCL) 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).
Selinexor is indicated:
- In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy
- In combination with dexamethasone, for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least 4 prior therapies and whose disease is refractory to at least 2 proteasome inhibitors (PI), at least 2 immunomodulatory agents (IMiD), and an anti-CD38 monoclonal antibody (mAb)
- 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
PQI Process:
Upon receiving a new prescription for selinexor
- Confirm appropriate dosing and schedule based on diagnosis and prescribed regimen (MM, RR-MM or RR-DLBCL)
- Confirm receipt of dexamethasone (requirement for RR-MM indication only)
- Confirm prophylactic anti-emetic for moderate to high emetogenicity
- Advise patients to maintain adequate fluid and caloric intake throughout treatment. Consider intravenous hydration for patients at risk of dehydration
- Provide prophylactic antiemetics. Administer a 5-HT3 receptor antagonist and other anti-nausea agents (such as NK-1 RA and/or olanzapine) prior to and during treatment with selinexor
- Ensure appropriate monitoring with a CBC, CMP, and body weight at baseline, then at least weekly for the first 3 months, 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
- Potential side effects involved with utilizing bortezomib in combination (peripheral neuropathy, blurred vision)
- Educate patients on side effects and report adverse effects to prescriber
Dosing:
- RR-MM in combination with dexamethasone Xd: 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
- MM in combination with bortezomib and dexamethasone XVd: Selinexor is 100 mg (2 x 50mg) by mouth once weekly on day 1 of each week until disease progression or unacceptable toxicity. Bortezomib 1.3 mg/m2 administered subcutaneously once weekly on Day 1 of each week for 4 weeks followed by 1 week off. Dexamethasone 20mg by mouth twice weekly on Days 1 and 2 of each week
- RR-DLBCL: Selinexor 60 mg (3 x 20 mg tablets) by mouth twice weekly on days 1 and 3 until disease progression or unacceptable toxicity
Supportive Care/Adverse Effect Management
Xd Dose Reduction Steps for RR-MM Adverse Reactions
| Selinexor starting dose | 1st Reduction | 2nd Reduction | 3rd 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% had a dose interrupted3
XVd Dose Reduction Steps for MM Adverse Reactions
| Selinexor starting dose | 1st Reduction | 2nd Reduction | 3rd Reduction |
Discontinue |
| 100 mg ONCE Weekly on Day 1 of each week (100 mg total per week) | 80 mg ONCE Weekly | 60 mg ONCE Weekly | 40 mg ONCE Weekly |
64% of patients had a reduction in dose, and 83% had a dose interrupted3
Dose Reduction Steps for RR-DLBCL Adverse Reactions5
| Selinexor starting dose | 1st Reduction | 2nd Reduction | 3rd Reduction |
Discontinue |
| 60 mg Days 1 and 3 of each week (120 mg total per week) | 40 mg Days 1 and 3 of each week (80 mg total per week) | 60 mg ONCE Weekly | 40 mg ONCE Weekly |
49% of patients had a reduction in dose, and 61% had a dose interrupted5
- 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® or Ensure®
- Consider addition of low dose olanzapine and/or megesterol acetate
Patient Centered Activities:
- Provide Oral Chemotherapy Education (OCE) sheet
- Consider providing Selinexor (Xpovio®) Treatment Support Kit (TSK)
- Ensure patient knows dosing schedule including dexamethasone and prophylactic anti-nausea medications
- Ensure patient knows to swallow the tablet whole with water, tablet should not be broken/chewed/crushed/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
References:
- 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.
- 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.
- Xpovio® (selinexor) [package insert]. Newton, MA: Karyopharm Therapeutics Inc.
- 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.
- Kalakonda N, Maerevoet M, Cavallo F, et al. Selinexor in patients with relapsed or refractory diffuse large B-cell lymphoma (SADAL): a single-arm, multinational, multicentre, open-label, phase 2 trial. Lancet Haematol 2020; 7: e511–22.
