AHFS Class:

• Antineoplastic Agents 10:00

Generic Name(s):

• Selinexor

Selinexor, a selective inhibitor of nuclear export, is an antineoplastic agent.1

Relapsed or Refractory Multiple Myeloma

Selinexor is used in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma in patients 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.1,  2,  13 Selinexor is also used in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.1,  14 Selinexor has been designated an orphan drug by FDA for the treatment of this cancer.10 Guidelines recommend triplet therapy with 2 novel agents (immunomodulatory drug, proteasome inhibitor, or monoclonal antibody) plus a steroid, with no preference given to a specific regimen for relapsed or refractory multiple myeloma treatment.15

Clinical Experience

Relapsed or Refractory Multiple Myeloma in Combination with Dexamethasone

The current indication for selinexor is based principally on efficacy and safety data from a prespecified subgroup analysis of 83 patients who were enrolled in a multicenter, open-label, single-arm phase 2 study (STORM; NCT02336815).1,  2 Part 2 of the STORM study enrolled 122 adults with relapsed or refractory multiple myeloma who had previously received 3 or more treatment regimens for their disease and whose disease was documented to be refractory to corticosteroids, a proteasome inhibitor (i.e., bortezomib and/or carfilzomib), at least one immunomodulatory agent (i.e., lenalidomide and/or pomalidomide), an anti-CD38 monoclonal antibody (e.g., daratumumab), and to their most recent line of therapy.1,  2 The subgroup of 83 patients had disease that was refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab.1 Patients received selinexor (80 mg) in combination with dexamethasone (20 mg) on days 1 and 3 of each week until disease progression, death, or unacceptable toxicity occurred.1 The median age of the subgroup of 83 patients in the study was 65 years; the median time since diagnosis was 7 years and patients had received a median of 8 prior therapies for their disease.1 Most (81%) of these patients had undergone stem cell transplantation and 57% had high-risk cytogenetics.1

The primary efficacy end point of this study was overall response rate as assessed by an independent review committee according to the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma.1,  2 Because selinexor was associated with substantial toxicities, the benefit-to-risk assessment appeared to be more favorable in patients in this subgroup of 83 patients with more heavily pretreated disease (i.e., refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab) than in the overall trial population.1,  12 The overall response rate (stringent complete, complete, very good partial, and partial responses) was 25.3% in these patients.1 There were no complete responses; however, one patient achieved a stringent complete response.1 The median time to first response was 4 weeks, with a range of 1-10 weeks, and the median duration of response was 3.8 months.1 Health-related quality of life measures demonstrated a lack of decline over 6 cycles of treatment and treatment responders had less decline from baseline compared to non-responders.13

Relapsed or Refractory Multiple Myeloma in Combination with Bortezomib and Dexamethasone

The indication for use of selinexor in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least 1 prior therapy is based on efficacy and safety data from a multicenter, randomized, open-label, active-controlled trial (BOSTON; NCT03110562).1,  14 Four hundred and two patients with multiple myeloma who received 1-3 previous therapies were randomized to receive either selinexor 100 mg once weekly plus bortezomib 1.3 mg/m² once weekly plus dexamethasone 20 mg twice weekly or bortezomib 1.3 mg/m² twice weekly plus dexamethasone 20 mg four times weekly for 8 cycles followed by bortezomib 1.3 mg/m² once weekly plus dexamethasone 20 mg twice weekly.1,  14 Treatment continued in both arms until disease progression or unacceptable toxicity occurred.1,  14 In the selinexor-treated and bortezomib-dexamethasone only group, the median age was 66 and 67 years, respectively; the median time since diagnosis was 3.81 and 3.59 years, respectively; and approximately 30% of patients in both groups had received 2 prior therapies.1,  14 About 70% of patients in both groups had previously received bortezomib and up to 50% had high-risk cytogenetics.1,  14

The primary efficacy end point of this study was progression free survival (PFS) as assessed by an independent review committee according to the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma.1,  14 Progression-free survival was 13.9 months in the selinexor-treated group and 9.5 months in the bortezomib-dexamethasone only group.1,  14 The overall response rate was 76.4 and 62.3% with the selinexor-treated group compared to the bortezomib-dexamethasone only group with complete response in 7 and 4%, respectively.1,  14 The median time to response was 1.4 and 1.6 months in the selinexor-treated and bortezomib-dexamethasone only groups, respectively and the median duration of response was 20.3 and 12.9 months, respectively.1,  14

Clinical Perspective

In 2019, the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario published evidence-based recommendations on the treatment of multiple myeloma in patients who are transplant-eligible, transplant-ineligible, and those with relapsed or refractory disease.15 For treatment of relapsed or refractory disease, the guideline recommends triplet therapy with 2 novel agents (immunomodulatory drug, proteasome inhibitor, or monoclonal antibody) plus a steroid (evidence quality: high; strength of recommendation: strong).15 Choice of therapy should be based on patient, disease, and treatment factors, including prior therapies.15 No preference of one regimen over another is given due to lack of comparative trials.15

Relapsed or Refractory Diffuse Large B-Cell Lymphoma

Selinexor is used 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.1,  16,  17,  18 The accelerated approval of selinexor for this indication is based on response rate; continued FDA approval for this indication may be contingent on verification and description of clinical benefit of selinexor in a confirmatory study.1 Selinexor has been designated an orphan drug by FDA for the treatment of DLBCL.10

Clinical Experience

The indication for use of selinexor for the treatment of adult patients with relapsed or refractory DLBCL is based on efficacy and safety data from a multicenter, single-arm, open-label study (SADAL; NCT02227251) of 134 patients with DLBCL refractory to 2 to 5 previous treatment regimens.1,  16 Patients received selinexor 60 mg on days 1 and 3 of each week until disease progression or unacceptable toxicity.1,  16 The median age of patients was 67 years, 59% were male, 79% were white, and 7% were Asian.1,  16 Most patients (88%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.1,  16 De novo DLBCL was the diagnosis in 75% of patients and 23% had transformed DLBCL.1,  16 The median number of prior therapies was 2; 63% received 2 prior therapies, 24% received 3 prior therapies, and 10% received 4 or 5 prior therapies.1 Thirty percent of patients had prior autologous hematopoietic stem-cell transplantation (HSCT).1,  16

The primary efficacy end point of this study was overall response rate and duration of response as assessed by an independent review committee according to the Lugano 2014 criteria.1,  16 The overall response rate (complete and partial response) was 29% in these patients.1,  16 Complete responses occurred in 13% of patients.1,  16 The percentage of patients with a duration of response of 3, 6, and 12 months was 56, 38, and 15%, respectively.1 The median time to first response was 8.1 (range: 6.7-16.4) weeks.1,  16 Increases in health-related quality of life measures were observed starting with the third cycle of treatment and were maintained with selinexor therapy.17

A subgroup analysis demonstrated a median overall survival of 11.1 months in patients less than 70 years compared to 7.8 months in patients 70 years or older.18 Patients refractory to their most recent treatment had a median overall survival of 7 months versus 11.1 months for patients not refractory to the most recent treatment.18 Median overall survival was 10.9 and 7.8 months in patients with or without prior autologous stem cell transplantation (ASCT), respectively.18

Other Uses

Selinexor has been designated an orphan drug by FDA for the treatment of glioblastoma†,   soft tissue sarcoma†,   and acute myeloid leukemia†.10

General

Pretreatment Screening

• Obtain platelet count prior to initiating therapy.1
• Obtain white blood cell count with differential prior to initiating therapy.1
• Check patient's weight and nutritional and volume status prior to initiating therapy.1
• Obtain sodium level prior to initiation of therapy.1
• Perform a pregnancy test prior to initiating therapy in females of reproductive potential; if positive, advise patient of the potential risk to the fetus1

Patient Monitoring

• Monitor platelet counts throughout treatment and more frequently in the first 3 months of treatment.1 Monitor patients for signs and symptoms of bleeding and evaluate promptly.1
• Monitor white blood cell counts with differential throughout treatment and more frequently in the first 3 months of treatment.1 Monitor patients for signs and symptoms of concomitant infection and evaluate promptly.1
• Monitor weight and nutritional and volume status throughout treatment and more frequently in the first 3 months of treatment.1
• Monitor for diarrhea.1
• Monitor sodium level throughout treatment and more frequently in the first 2 months of treatment.1
• Monitor for signs and symptoms of infection; evaluate and treat promptly.1
• Monitor for dizziness and mental status changes.1 Institute fall precautions as appropriate.1
• Monitor for signs and symptoms of cataract.1

Premedication Prophylaxis

• Administer prophylaxis with a type 3 serotonin (5-HT₃) receptor antagonist and/or other antiemetics prior to and during treatment with selinexor.1

Other General Considerations

• Advise patients to maintain adequate fluid and caloric intake throughout selinexor treatment.1 Consider IV hydration for patients at risk of dehydration.1

Administration

Selinexor is administered orally, either once weekly (if used in combination with bortezomib and dexamethasone) or twice weekly (if used alone or in combination with dexamethasone).1 Each dose of selinexor should be taken with a dose of dexamethasone at approximately the same time of day.1 If a dose of selinexor is missed or delayed, take the next dose at the next regularly scheduled time.1 If a dose is vomited, do not repeat the dose and take the next dose on the next regularly scheduled day.1

Selinexor is commercially available as 20, 40, 50, and 60-mg tablets that are provided in several different therapy packs designed to provide a 4-week supply of specific indicated dosage regimens (i.e., 40, 60, or 80 mg twice weekly or 40, 60, 80, or 100 mg once weekly).1

Tablets of selinexor should be swallowed whole with water and should not be broken, chewed, crushed, or divided.1

Store selinexor at or below 30°C.1

Clinicians should consult the prescribing information for bortezomib and dexamethasone for additional information regarding administration of these agents.1

Dosage

Relapsed or Refractory Multiple Myeloma

When used in combination with dexamethasone, the recommended initial dosage of oral selinexor is 80 mg on days 1 and 3 of each week (i.e., 80 mg twice weekly; total of 160 mg each week).1 Each dose of selinexor should be administered concomitantly with dexamethasone; the manufacturer of selinexor recommends an initial dexamethasone dosage of 20 mg taken orally also on days 1 and 3 of each week.1 Combination therapy with selinexor and dexamethasone should be continued until disease progression or unacceptable toxicity occurs.1

When used in combination with bortezomib and dexamethasone, the recommended dosage of selinexor is 100 mg orally once weekly on day 1 of each week in combination with:

• Bortezomib 1.3 mg/m² administered subcutaneously once weekly on day 1 of each week for 4 weeks followed by 1 week off.1
• Dexamethasone 20 mg orally twice weekly on days 1 and 2 of each week.1

Relapsed or Refractory Diffuse Large B-Cell Lymphoma

The recommended dosage of selinexor is 60 mg on days 1 and 3 of each week until disease progression or unacceptable toxicity.1

Dosage Modification for Toxicity

Tables 1 to 4 provide recommendations for dosage modifications for selinexor based on indication for use and type of toxicity. 1 The prescribing information for dexamethasone should be consulted for dosage modifications for adverse reactions associated with dexamethasone.1

Special Populations

Hepatic Impairment

The manufacturer makes no specific dosage recommendations for patients with hepatic impairment. 1

Renal Impairment

The manufacturer makes no specific dosage recommendations for patients with renal impairment. 1

Geriatric Patients

The manufacturer makes no specific dosage recommendations for geriatric patients.1

Contraindications

• The manufacturer states that there are no known contraindications to the use of selinexor.1

Warnings/Precautions

Thrombocytopenia

Selinexor commonly causes thrombocytopenia, which can lead to potentially fatal hemorrha 1,  11 thrombocytopenia appears to be a dose-related adverse effect.1,  11 Thrombocytopenia was reported in 74% of patients and grade 3 or 4 thrombocytopenia was reported in 61% of patients receiving selinexor 80 mg twice weekly (STORM study) for relapsed or refractory multiple myeloma.1,  2,  3 Bleeding occurred in 23% and clinically significant bleeding occurred in 5% of patients with thrombocytopenia.1 Fatal hemorrhage was reported in fewer than 1% of patients with thrombocytopenia.1 The median time to onset of thrombocytopenia was 22 days.1 Selinexor-associated thrombocytopenia appears to be due, at least in part, to inhibition of thrombopoietin signaling in early megakaryopoiesis.2,  11

In the BOSTON study, thrombocytopenia was reported in 92% of patients and grade 3 or 4 thrombocytopenia was reported in 43% of patients with multiple myeloma receiving selinexor 100 mg weekly. 1 Bleeding occurred in 16% and clinically significant bleeding (grade ≥3) occurred in 4% of patients with thrombocytopenia.1 Fatal hemorrhage occurred in 2% of patients with thrombocytopenia.1 Permanent discontinuation of selinexor due to thrombocytopenia occurred in 2% of patients. 1 The median time to first onset of thrombocytopenia was 22 days for any grade thrombocytopenia and 43 days for grade 3 or 4 thrombocytopenia.1

In patients with diffuse large B-cell lymphoma (DLBCL), thrombocytopenia developed or worsened in 86% of patients, including grade 3 or 4 thrombocytopenia in 49% of patients (SADAL study).1 The median time to first onset of thrombocytopenia was 28 days for any grade thrombocytopenia and 33 days for grade 3 or 4 thrombocytopenia. 1

Monitor platelet counts at baseline, during therapy, and as clinically indicated in patients treated with selinexor.1 More frequent monitoring is recommended during the first 3 months of therapy.1 Monitor for signs and symptoms of bleeding, and promptly evaluate any bleeding.1 Administer platelet transfusions and/or other supportive care (e.g., thrombopoietin-receptor agonists such as romiplostim and eltrombopag) as clinically indicated.1,  2,  3,  11 Interrupt treatment, reduce dose, or permanently discontinue selinexor therapy based on the severity of thrombocytopenia.1,  11

Neutropenia

Selinexor can cause life-threatening neutropenia, potentially increasing the risk of infection.1 Neutropenia was reported in 34% of patients and severe (grade 3 or 4) neutropenia was reported in 21% of patients with multiple myeloma receiving selinexor 80 mg twice weekly (STORM study).1,  2,  3 The median time to onset of the first neutropenic event was 25 days.1 Febrile neutropenia was reported in 3% of patients.1

In the BOSTON study, neutropenia was reported in 48% of patients and severe (grade 3 or 4) neutropenia was reported in 12% of patients with multiple myeloma receiving selinexor 100 mg once weekly.1 The median time to onset of the first neutropenic event was 23 days and 40 days for grade 3 or 4 neutropenia.1 Febrile neutropenia was reported in <1% of patients.1 In patients with DLBCL (SADAL study), grade 3 or 4 neutropenia developed in 21 or 9% of patients, respectively. 1 The median time to first onset for grade 3 or 4 neutropenia was 32 days. 1 Febrile neutropenia was reported in 3% of patients. 1

Monitor neutrophil counts at baseline, during selinexor therapy, and as clinically indicated.1 More frequent monitoring is recommended during the first 3 months of therapy.1 Monitor for signs or symptoms of infection and evaluate promptly.1 Administer supportive care, including anti-infective agents for signs of infection and use of growth factors such as granulocyte colony-stimulating factors (G-CSFs) to treat the neutropenia as clinically indicated.1 Interrupt treatment, reduce dose, or permanently discontinue selinexor therapy based on the severity of neutropenia.1

GI Toxicity

Selinexor can cause severe GI toxicities.1 In patients with DLBCL (SADAL study), grade 3 and 4 GI toxicity occurred in 80 and 13% of patients, respectively.1

Nausea/Vomiting

In patients with multiple myeloma (STORM study), nausea was reported in 72% of patients and grade 3 nausea was reported in 9% of patients treated with selinexor 80 mg twice weekly with use of antiemetic prophylaxis.1,  2,  3 Vomiting was reported in 41% of patients and grade 3 vomiting was reported in 4% of patients treated with the drug.1,  2,  3 The median time to onset of the first nausea or vomiting event was 3 or 5 days, respectively.1

In the BOSTON study, nausea was reported in 50% of patients and grade 3 nausea was reported in 8% of patients treated with selinexor once weekly with use of antiemetic prophylaxis.1 Vomiting was reported in 21% of patients and grade 3 vomiting was reported in 4.1% of patients.1 The median time to onset of the first nausea or vomiting event was 6 or 8 days, respectively.1 Permanent discontinuation due to nausea occurred in 3.1% of patients and due to vomiting occurred in 2.1% of patients. 1

In patients with DLBCL (SADAL study), nausea was reported in 57% of patients and grade 3 nausea was reported in 6% of patients who received selinexor and antiemetic prophylaxis. 1 Vomiting was reported in 28% of patients and grade 3 vomiting was reported in 1.5% of patients.1 The median time to onset of the first nausea or vomiting event was 3 or 7 days, respectively.1

Administer prophylaxis with a type 3 serotonin (5-HT₃) receptor antagonist and/or other antiemetics prior to and during treatment with selinexor.1 Manage nausea and/or vomiting with interruption, dosage reduction, and/or discontinuance of selinexor therapy.1 Administer IV fluids and electrolyte replacement to patients at risk of dehydration.1 Administer additional antiemetics as clinically indicated.1

Diarrhea

In patients with multiple myeloma, diarrhea was reported in 44% of patients and grade 3 diarrhea was reported in 6% of patients treated with selinexor 80 mg twice weekly (STORM study).1,  2,  3 The median time to onset of diarrhea was 15 days.1

In the BOSTON study, diarrhea was reported in 32% of patients and grade 3 diarrhea was reported in 6% of patients treated with selinexor once weekly. 1 The median time to onset of diarrhea was 50 days.1 Permanent discontinuation due to diarrhea occurred in 1% of patients. 1

In patients with DLBCL (SADAL study), diarrhea was reported in 37% of patients and grade 3 diarrhea was reported in 3% of patients treated with selinexor. 1 The median time to onset of diarrhea was 12 days.1

Manage diarrhea with treatment interruption, dosage reduction, or permanent discontinuation of selinexor depending on the severity of the adverse reaction.1 Provide standard antidiarrheal agents, IV fluids to prevent dehydration, and replace electrolytes as clinically indicated.1

Anorexia/Weight Loss

Anorexia was reported in 53% of patients and grade 3 anorexia was reported in 5% of patients treated with selinexor 80 mg twice weekly (STORM study) for multiple myeloma.1,  2,  3 Weight loss was reported in 47% of patients and grade 3 weight loss was reported in 1% of patients treated with selinexor.1 The median time to onset of anorexia or weight loss was 8 or 15 days, respectively.1

In the BOSTON study, anorexia was reported in 35% of patients and grade 3 anorexia was reported in 3.6% of patients treated with selinexor 100 mg once weekly for multiple myeloma.1 Weight loss was reported in 26% of patients and grade 3 weight loss was reported in 2.1% of patients treated with selinexor.1 The median time to onset of anorexia or weight loss was 35 or 58 days, respectively.1 Permanent discontinuation due to anorexia or weight loss was reported in 2.1% or 1% of patients, respectively.1

In patients with DLBCL, anorexia was reported in 37% of patients and grade 3 anorexia was reported in 3.7% of patients treated with selinexor.1 Weight loss (grade 1 or 2) was reported in 30% of patients. 1

Monitor body weight and nutritional and volume status at baseline, during selinexor therapy, and as clinically indicated.1 More frequent monitoring is recommended during the first 3 months of therapy.1 Based on severity, manage anorexia and weight loss with treatment interruption, dosage reduction, or permanent discontinuation of selinexor.1 Provide nutritional support, fluids, and electrolyte repletion as clinically indicated.1

Hyponatremia

Selinexor can cause severe or life-threatening hyponatremia.1 Hyponatremia was reported in 39% of patients and grade 3 or 4 hyponatremia was reported in 22% of patients treated with selinexor 80 mg twice weekly (STORM study) for multiple myeloma.1,  2,  3 The median time to onset of the first event of hyponatremia was 8 days.1

In the BOSTON study, hyponatremia was reported in 58% of patients and grade 3 or 4 hyponatremia was reported in 14% of patients treated with selinexor 100 mg once weekly for multiple myeloma.1 The median time to onset was 21 days to the first event of any grade hyponatremia and 22 days to the first onset of grade 3 or 4 hyponatremia. 1

In patients with DLBCL, hyponatremia was reported in 62% of patients and grade 3 hyponatremia was reported in 16% of patients treated with selinexor. 1 Hyponatremia occurred in the context of GI toxicity such as nausea, vomiting, diarrhea, dehydration, and anorexia in approximately 63% of cases. 1

Monitor serum sodium concentrations at baseline, during selinexor therapy, and as clinically indicated.1 More frequent monitoring is recommended during the first 2 months of therapy.1 Correct sodium concentrations for concurrent hyperglycemia (serum glucose concentrations exceeding 150 mg/dL) and high serum paraprotein concentrations.1 Assess hydration status and treat hyponatremia as clinically appropriate (e.g., IV saline and/or oral sodium supplementation), including dietary review.1 Interrupt, reduce the dosage, or permanently discontinue selinexor therapy based on the severity of hyponatremia.1

Serious Infection

Selinexor can cause serious and fatal infections.1 Most of these infections were not associated with grade 3 or higher neutropenia.1 Reported atypical infections include, but are not limited to, fungal pneumonia and herpes virus infection. 1

Infections of any grade occurred in 52% of patients treated with selinexor 80 mg twice weekly (STORM study) for multiple myeloma.1 Grade 3 or higher infections were reported in 25% of patients, and deaths resulting from an infection occurred in 4% of patients.1 Upper respiratory tract infection of any grade, pneumonia, or sepsis occurred in 21, 13, or 6% of patients, respectively.1 The most commonly reported grade 3 or higher infections in patients receiving selinexor were pneumonia (9%) and sepsis (6%).1 The median time to onset of pneumonia or sepsis was 54 or 42 days, respectively.1

In the BOSTON study, infections of any grade occurred in 69% of patients treated with selinexor 100 mg once weekly for multiple myeloma.1 Grade 3 or higher infections were reported in 32% of patients, and deaths resulting from an infection occurred in 3.1% of patients.1 The most commonly reported grade 3 or higher infections in patients receiving selinexor were pneumonia (14%), sepsis (4.1%), and upper respiratory tract infection (3.6%).1

In patients with DLBCL (SADAL study), infections of any grade occurred in 49% of patients treated with selinexor. 1 Grade 3 or higher infections were reported in 25% of patients, and an infection-related serious adverse reaction occurred in 21% of patients.1 The most commonly reported grade 3 or higher infections in patients receiving selinexor were lower respiratory tract infections (9% including pneumonia in 6%) and sepsis (6%).1 The median time to onset of grade 3 or higher infections was 42 days.1

Monitor for signs and symptoms of infection and promptly treat any infection.1

Neurological Toxicity

Selinexor can cause life-threatening neurological toxicities. 1

Adverse neurologic effects, including dizziness, syncope, depressed level of consciousness, and mental status changes (including delirium and confusional state), occurred in 30% of patients and severe (grade 3 or 4) neurologic adverse effects occurred in 9% of patients treated with selinexor 80 mg twice weekly (STORM study) for multiple myeloma.1 The median time to the first neurologic adverse reaction was 15 days.1

In the BOSTON study, neurological adverse reactions (excluding peripheral neuropathy) including dizziness, syncope, depressed level of consciousness, vertigo, amnesia, and mental status changes (including delirium and confusional state), occurred in 26% of patients and severe (grade 3 or 4) neurologic adverse effects occurred in 3.6% of patients treated with selinexor 100 mg once weekly for multiple myeloma.1 The median time to the first neurologic adverse reaction was 29 days.1 Permanent discontinuation due to neurological adverse reactions occurred in 2.1% of patients. 1

In patients with DLBCL, neurological adverse reactions occurred in 25% of patients and severe (grade 3 or 4) neurologic adverse effects occurred in 6% of patients treated with selinexor.1 The most frequent adverse reactions were dizziness (16%) and mental status changes (11%) which included confusion, cognitive disorders, somnolence, hallucination, delirium, and depressed level of consciousness. Syncope occurred in 2.2% of patients. The median time to the first neurologic adverse reaction was 28 days.1 Of patients with these adverse reactions, 68% recovered with a median time to recovery of 14 days. 1

Optimize hydration status, hemoglobin concentrations, and concomitant drug therapy during selinexor therapy to avoid potential exacerbation of dizziness or mental status changes.1 Advise patients to avoid situations where dizziness or confusional state may be dangerous such as driving or operating heavy machinery until symptoms have resolved.1 When indicated, implement fall precautions.1

Embryofetal Toxicity

Selinexor can cause fetal harm based on its mechanism of action and animal findings.1 Teratogenicity and growth alterations were observed when the drug was administered to pregnant animals during the period of organogenesis at exposures below those achieved in humans at the recommended dosage.1

Assess pregnancy status prior to initiation of selinexor therapy.1 Advise women of reproductive potential and men who are partners of such women to use effective contraception during treatment with selinexor and for 1 week after the last dose.1 Apprise pregnant women of the potential risk to the fetus.1

Cataract

New onset or exacerbation of cataract has occurred during treatment with selinexor. 1

In the BOSTON study, new onset or worsening cataract requiring clinical intervention was reported in 22% of patients treated with selinexor 100 mg once weekly for multiple myeloma. 1 The median time to new onset of cataract was 228 days and 237 days for worsening cataract in patients presenting with cataract at the start of selinexor treatment. 1 Surgical removal of the cataract is usually required for treatment of cataracts.1

Inform patients to report any changes in vision. 1

Specific Populations

Pregnancy

Based on its mechanism of action and animal findings, selinexor can cause fetal harm if administered to pregnant women.1

Lactation

It is not known whether selinexor or its metabolites are distributed into milk.1 The effects of the drug or its metabolites on nursing infants or on milk production also are not known.1

Because of the potential for serious adverse reactions to selinexor in nursing infants, women should be advised to discontinue nursing while receiving selinexor and for 1 week after the last dose of the drug.1

Females and Males of Reproductive Potential

The pregnancy status of females of reproductive potential should be verified before starting selinexor treatment. 1 During treatment, females of reproductive potential or males with a female partner of reproductive potential should use effective contraception during selinexor treatment and for 1 week after the last dose. 1

Selinexor may impair fertility in males and females of reproductive potential. 1

Pediatric Use

Safety and efficacy of selinexor have not been established in pediatric patients.1

Geriatric Use

Of the 202 patients with relapsed or refractory multiple myeloma treated with selinexor in the STORM study, 49% were 65 years of age or older and 11% were 75 years of age or older.1 Although no overall differences in effectiveness were observed between geriatric patients (including patients over 75 years of age) and younger adults, patients 75 years of age or older had a higher incidence of serious adverse reactions (70 versus 58%) and fatal adverse reactions (17 versus 9%) and a higher incidence of discontinuation due to adverse reactions (44 versus 27%) compared with younger adults.1

In the BOSTON study (n=195), 56% of patients who received selinexor were 65 years of age and older and 17% were 75 years of age and older. 1 Although no overall differences in effectiveness were observed between older and younger patients, those who were 65 years of age or older had a higher incidence of serious adverse reactions (56 versus 47%) and a higher incidence of discontinuation due to adverse reactions (28 versus 13%) compared with younger adults.1

In the study evaluating patients with DLBCL who received selinexor (SADAL study; n=134), 61% of patients were 65 years of age and older and 25% were 75 years of age and older. 1 The number of patients 65 years of age and older with DLBCL treated with selinexor in clinical studies is insufficient to determine whether they respond differently from younger patients. 1

Patient age (18-94 years) does not appear to substantially affect selinexor pharmacokinetics.1

Hepatic Impairment

Mild hepatic impairment does not have clinically important effects on the pharmacokinetics of selinexor.1

The effect of moderate or severe hepatic impairment on selinexor pharmacokinetics is not known.1

Renal Impairment

Mild to severe renal impairment (creatinine clearance of 15-89 mL/minute) did not have clinically important effects on the pharmacokinetics of selinexor.1

The effect of end-stage renal disease (creatinine clearance of less than 15 mL/minute) or hemodialysis on selinexor pharmacokinetics is not known.1

Common Adverse Effects

Adverse effects reported in at least 20% of patients receiving selinexor in combination with dexamethasone for relapsed or refractory multiple myeloma include thrombocytopenia, fatigue, nausea, anemia, decreased appetite, weight loss, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.1

Adverse effects reported in at least 20% of patients receiving selinexor in combination with bortezomib and dexamethasone for multiple myeloma include fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, weight loss, cataract, and vomiting. 1 Grade 3 or 4 laboratory abnormalities reported in at least 10% of patients include thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia, and neutropenia. 1

Adverse effects reported in at least 20% of patients receiving selinexor for treatment of DLBCL, include fatigue, nausea, diarrhea, decreased appetite, weight loss, constipation, vomiting, and pyrexia. 1 Grade 3 or 4 laboratory abnormalities reported in at least 15% of patients include thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. 1

Selinexor is a substrate of cytochrome P-450 (CYP) isoenzyme 3A4, uridine diphosphate-glucuronosyltransferases (UGTs), and glutathione S-transferases (GSTs).1

Selinexor does not inhibit CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, or 3A4/5 nor does it induce CYP isoenzymes 3A4, 1A2, or 2B6 in vitro.1 Selinexor inhibits organic anion transporting polypeptide (OATP) 1B3 but does not inhibit other solute carrier (SLC) transporters.1

Selinexor is not a substrate of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), OATP1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2, multidrug and toxin extrusion (MATE) 1, or MATE2-K.1

Acetaminophen

No significant change in selinexor pharmacokinetics was observed with co-administration of up to a daily dose of 1000 mg acetaminophen. 1

Description

Selinexor, a selective inhibitor of nuclear export, is an antineoplastic agent.1,  2,  4,  6,  8 The drug inhibits exportin 1 (XPO1; also known as chromosomal region maintenance 1 [CRM1]), which is a nuclear exporter protein that transports macromolecules such as tumor suppressor proteins (e.g., p53), cell cycle regulators, and messenger RNAs (mRNAs) encoding for oncogenic proteins (e.g., c-myc, cyclin D1) from the nucleus to the cytoplasm.1,  2,  3,  4,  5,  6,  7,  8 XPO1 overexpression is observed in a variety of malignancies, including multiple myeloma, and is associated with poor prognosis in multiple myeloma.2,  4,  5,  6,  7 Selinexor covalently binds to and inhibits XPO1 in a slowly reversible manner, resulting in retention and activation of tumor suppressor proteins in the nucleus, inhibition of oncogenic mRNA translation and oncogenic protein synthesis, cell cycle arrest, and apoptosis of cancer cells.1,  2,  4,  5 In preclinical studies, selinexor demonstrated proapoptotic activity in vitro in multiple myeloma cell lines and patient tumor samples and antitumor activity in murine xenograft models.1,  2,  8

Following oral administration, peak plasma concentrations of selinexor are achieved within 4 hours.1 Peak plasma concentrations and area under the plasma concentration-time curve (AUC) are dose proportional over a dose range of 3-85 mg/m² (0.05-1.44 times the recommended dose based on a body surface area of 1.7 m²).1 Administration with a high-fat meal does not have clinically important effects on the pharmacokinetics of selinexor.1 The drug is 95% bound to plasma proteins.1 Selinexor is metabolized by cytochrome P-450 (CYP) isoenzyme 3A4 and multiple UDP-glucuronosyltransferases (UGTs) and glutathione S-transferases (GSTs).1 The mean elimination half-life of the drug is 6-8 hours.1 Age (18-94 years), sex, body weight (36-168 kg), disease type (hematological non-diffuse large B-cell lymphoma [DLBCL], solid tumor, DLBCL), and race/ethnicity do not have clinically important effects on the pharmacokinetics of selinexor.1

Advice to Patients

• Advise patients to read the manufacturer's medication guide.1
• Instruct patients to take selinexor exactly as prescribed.1 Tablets should be swallowed whole with water and should not be broken, chewed, crushed, or divided.1
• If a dose is missed or delayed or if vomiting occurs after a dose is taken, the next dose should be taken at the next regularly scheduled time and day.1 An extra dose should not be taken to replace a missed or vomited dose.1
• Advise patients of the importance of patients taking concomitant dexamethasone and prophylactic antiemetics exactly as prescribed.1
• Advise patients that blood tests and body weight will be monitored at baseline and during treatment as clinically indicated, and monitoring will be more frequent during the first 3 months of treatment.1
• Risk of hematologic adverse effects, including thrombocytopenia, anemia, and neutropenia.1 Inform patients to contact their clinician if signs or symptoms of thrombocytopenia (e.g., bleeding, easy bruising), anemia (e.g., fatigue, shortness of breath), or neutropenia (e.g., infection) occur.1
• Risk of adverse GI effects such as nausea, vomiting, and diarrhea.1 Inform patients to contact their clinician if any of these adverse reactions occur or persist.1
• Inform patients that fatigue commonly occurs during selinexor therapy.1
• Risk of weight loss and decreased appetite.1 Advise patients to report decreased appetite and weight loss to their clinician.1
• Inform patients to maintain appropriate fluid and caloric intake during selinexor therapy.1
• Risk of confusion and dizziness.1 Advise patients to immediately notify their clinician if symptoms of neurological toxicity occur.1 Inform patients to avoid driving or operating machinery until effects of the drug are known.1
• Risk of hyponatremia.1 Inform patients that hyponatremia may not be associated with specific symptoms.1
• Risk of serious infections.1 Instruct patients to notify their clinician if infection-related signs or symptoms (e.g., chills, fever) occur.1
• Risk of fetal harm.1 Advise women of reproductive potential and men with female partners of reproductive potential to use effective contraception during selinexor therapy and for 1 week after the last dose of the drug.1 Advise patients to inform their clinicians if they are pregnant or think they may be pregnant.1
• Risk of new or worsening cataracts. Advise patients to inform their clinician of any changes in their vision.1
• Advise women to avoid breast-feeding during selinexor therapy and for 1 week after the last dose of the drug.1
• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.1
• Advise patients of other important precautionary information.1

Additional Information

For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web]. The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. Karyopharm Therapeutics Inc. Xpovio^® (selinexor) tablets prescribing information. Newton, MA; 2025 Mar.

2. Chari A, Vogl DT, Gavriatopoulou M et al. Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma. N Engl J Med . 2019; 381:727-738. [PubMed 31433920]

3. Vogl DT, Dingli D, Cornell RF et al. Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma. J Clin Oncol . 2018; 36:859-866. [PubMed 29381435]

4. Gandhi UH, Senapedis W, Baloglu E et al. Clinical Implications of Targeting XPO1-mediated Nuclear Export in Multiple Myeloma. Clin Lymphoma Myeloma Leuk . 2018; 18:335-345. [PubMed 29610030]

5. Sun Q, Chen X, Zhou Q et al. Inhibiting cancer cell hallmark features through nuclear export inhibition. Signal Transduct Target Ther . 2016; 1:16010. [PubMed 29263896]

6. Gravina GL, Senapedis W, McCauley D et al. Nucleo-cytoplasmic transport as a therapeutic target of cancer. J Hematol Oncol . 2014; 7:85. [PubMed 25476752]

7. Das A, Wei G, Parikh K et al. Selective inhibitors of nuclear export (SINE) in hematological malignancies. Exp Hematol Oncol . 2015; 4:7. [PubMed 25745591]

8. Parikh K, Cang S, Sekhri A et al. Selective inhibitors of nuclear export (SINE)--a novel class of anti-cancer agents. J Hematol Oncol . 2014; 7:78. [PubMed 25316614]

9. Karyopharm Therapeutics, Inc. Xpovio^® (selinexor) product information. From Xpovio^® website. [Web]

10. US Food and Drug Administration. Search orphan drug designations and approvals. From FDA website. [Web]

11. Machlus KR, Wu SK, Vijey P et al. Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis. Blood . 2017; 130:1132-1143. [PubMed 28630120]

12. Food and Drug Administration. Center for Drug Evaluation and Research. Application number 212306Orig1s000: Multi-discipline Review. From FDA website. [Web]

13. Tremblay G, Daniele P, Breeze J, et al. Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study. BMC Cancer . 2021;21(1):993.

14. Grosicki S, Simonova M, Spicka I, et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet . 2020;396(10262):1563-1573.

15. Mikhael J, Ismaila N, Cheung MC, et al. Treatment of multiple myeloma: ASCO and CCO joint clinical practice guideline. J Clin Oncol . 2019; 37:1228-63. [PubMed 30932732]

16. 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(7):e511-e522.

17. Shah J, Shacham S, Kauffman M, et al. Health-related quality of life and utility outcomes with selinexor in relapsed/refractory diffuse large B-cell lymphoma. Future Oncol . 2021;17(11):1295-1310.

18. Maerevoet M, Zijlstra JM, Follows G, et al. Survival among patients with relapsed/refractory diffuse large B cell lymphoma treated with single-agent selinexor in the SADAL study. Hematol Oncol . 2021;14(1):111.