Active Ingredient: Selinexor
Selinexor is indicated in combination with dexamethasone for the treatment of multiple myeloma in adult patients who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, two immunomodulatory agents and an anti-CD38 monoclonal antibody, and who have demonstrated disease progression on the last therapy.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral, 80 milligrams selinexor, 2 times weekly.
The recommended selinexor and dexamethasone starting doses are as follows:
Treatment with selinexor combined with dexamethasone should be continued until disease progression or unacceptable toxicity.
For information regarding the posology of medicinal products administered with selinexor, refer to the Summary of Product Characteristics (SmPC) for these medicinal products.
If a selinexor dose is missed or delayed or a patient vomits after a dose of selinexor, the patient should not repeat the dose. Patients should take the next dose on the next regularly scheduled day.
Recommended selinexor dose modifications for adverse reactions are presented in Table 1 and Table 2.
For information regarding dosage modification of medicinal products administered with selinexor, refer to their corresponding SmPC.
Table 1. Prespecified dose modification steps for adverse reactions:
| Selinexor in combination with Bortezomib and Dexamethasone (SVd) | Selinexor in combination with Dexamethasone (Sd) | |
| Recommended starting dose | 100 mg once weekly | 80 mg Days 1 and 3 of each week (160 mg total per week) |
| First reduction | 80 mg once weekly | 100 mg once weekly |
| Second reduction | 60 mg once weekly | 80 mg once weekly |
| Third reduction | 40 mg once weekly | 60 mg once weekly |
| Discontinue* | ||
* If symptoms do not resolve, treatment should be discontinued
Table 2. Dose modification guidelines for adverse reactions:
| Adverse reactiona | Occurrence | Action |
| Haematologic adverse reactions | ||
| Thrombocytopenia | ||
| Platelet count 25,000 to less than 75,000/mcL | Any | • Reduce selinexor by 1 dose level (see Table 1). |
| Platelet count 25,000 to less than 75,000/mcL with concurrent bleeding | Any | • Interrupt selinexor. • Restart selinexor at 1 dose level lower (see Table 1), after bleeding has resolved. |
| Platelet count less than 25,000/mcL | Any | • Interrupt selinexor. • Monitor until platelet count returns to at least 50,000/mcL. • Restart selinexor at 1 dose level lower (see Table 1). |
| Neutropenia | ||
| Absolute neutrophil count of 0.5 to 1.0 x 109/L without fever | Any | • Reduce selinexor by 1 dose level (see Table 1). |
| Absolute neutrophil count less than 0.5 x 109/L OR Febrile neutropenia | Any | • Interrupt selinexor. • Monitor until neutrophil counts return to 1.0 x 109/L or higher. • Restart selinexor at 1 dose level lower (see Table 1). |
| Anaemia | ||
| Haemoglobin less than 8.0 g/dL | Any | • Reduce selinexor by 1 dose level (see Table 1). • Administer blood transfusions and/or other treatments per clinical guidelines. |
| Life-threatening consequences (urgent intervention indicated) | Any | • Interrupt selinexor. • Monitor haemoglobin until levels return to 8 g/dL or higher. • Restart selinexor at 1 dose level lower (see Table 1). • Administer blood transfusions and/or other treatments per clinical guidelines. |
| Non-haematologic adverse reactions | ||
| Hyponatraemia | ||
| Sodium level 130 mmol/L or less | Any | • Interrupt selinexor and provide appropriate supportive care. • Monitor until sodium levels return to 130 mmol/L or higher. • Restart selinexor at 1 dose level lower (see Table 1). |
| Fatigue | ||
| Grade 2 lasting greater than 7 days OR Grade 3 | Any | • Interrupt selinexor. • Monitor until fatigue resolves to Grade 1 or baseline. • Restart selinexor at 1 dose level lower (see Table 1). |
| Nausea and vomiting | ||
| 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) | Any | • Maintain selinexor and initiate additional anti-nausea medicinal products. |
| Grade 3 nausea (inadequate oral caloric or fluid intake) OR Grade 3 or higher vomiting (6 or more episodes per day) | Any | • Interrupt selinexor. • Monitor until nausea or vomiting has resolved to Grade 2 or lower or baseline. • Initiate additional anti-nausea medicinal products. • Restart selinexor at 1 dose level lower (see Table 1). |
| Diarrhoea | ||
| Grade 2 (increase of 4 to 6 stools per day over baseline) | 1st | • Maintain selinexor and institute supportive care. |
| 2nd and subsequent | • Reduce selinexor by 1 dose level (see Table 1). • Institute supportive care. | |
| Grade 3 or higher (increase of 7 stools or more per day over baseline; hospitalization indicated) | Any | • Interrupt selinexor and institute supportive care. • Monitor until diarrhoea resolves to Grade 2 or lower. • Restart selinexor at 1 dose level lower (see Table 1). |
| Weight loss and anorexia | ||
| Weight loss of 10% to less than 20% OR Anorexia associated with significant weight loss or malnutrition | Any | • Interrupt selinexor and institute supportive care. • Monitor until weight returns to more than 90% of baseline weight. • Restart selinexor at 1 dose level lower (see Table 1). |
| Ocular adverse reactions | ||
| Grade 2, excluding cataract | Any | • Perform ophthalmologic evaluation. • Interrupt selinexor and provide supportive care. • Monitor until ocular symptoms resolve to Grade 1 or baseline. • Restart selinexor at 1 dose level lower (see Table 1). |
| Grade ≥3, excluding cataract | Any | • Permanently discontinue selinexor. • Perform ophthalmologic evaluation. |
| Other non-haematologic adverse reactions | ||
| Grade 3 or 4 (life threatening) | Any | • Interrupt selinexor. • Monitor until resolved to Grade 2 or lower. • Restart selinexor at 1 dose level lower (see Table 1). |
a National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03.
Selinexor in combination with dexamethasone (Sd) should be taken at approximately the same time on Days 1 and 3 of each week.
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