Selinexor is a nuclear export inhibitor. It is indicated in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma in adult patients who have received at least 4 prior therapies and have refractory disease to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody. Selinexor is indicated in combination with bortezomib and dexamethasone in adult patients who have received at least 1 prior therapy. Selinexor is also approved for the treatment of relapsed or refractory diffuse large B-cell lymphoma in adult patients who have had at least 2 lines of prior systemic therapy. Myelosuppression and hyponatremia have been reported with selinexor therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Emetic Risk
-Moderate/High
-Administer routine antiemetic prophylaxis prior to treatment.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
-Take selinexor with or without food at approximately the same time each day.
-Swallow tablets whole with water; do not break, chew, crush, or divide the tablets.
-If a dose is missed or delayed, take the next dose at the next regularly scheduled time.
-If vomiting occurs, do not repeat the dose; take the next dose at the next regularly scheduled time.
Severe hematologic toxicity including thrombocytopenia/decreased platelet count (74% to 92%), anemia/decreased hematocrit level (59% to 82%), lymphopenia/decreased lymphocyte count (15% to 77%), neutropenia/decreased neutrophil count (34% to 58%), and febrile neutropenia (3% or less) was reported with selinexor therapy in clinical studies. Obtain complete blood counts (CBC) with differential at baseline and throughout treatment; monitor CBCs more frequently during the first 3 months of treatment. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop severe myelosuppression. Administer blood or platelet transfusions, granulocyte-colony stimulating factors, or other medical treatment as clinically indicated. Thrombocytopenia (74%; grade 3 or 4, 61%), anemia (59%; grade 3 or 4, 40%), neutropenia (34%; grade 3 or 4, 21%), leukopenia (28%; grade 3 or 4, 11%), and lymphopenia (15%; grade 3 or 4, 10%) occurred in patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202). The median times to onset for thrombocytopenia and neutropenia were 22 and 25 days, respectively. Thrombocytopenia (92%; grade 3 or 4, 43%), anemia (71%; grade 3 or 4, 17%), neutropenia (48%; grade 3 or 4, 12%), lymphopenia (77%; grade 3 or 4, 38%), and febrile neutropenia (less than 1%) were reported in patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial. The median times to onset for thrombocytopenia and neutropenia were 28 and 23 days, respectively. Worsened thrombocytopenia (86%; grade 3 or 4, 49%), anemia (82%; grade 3 or 4, 25%), lymphopenia (63%; grade 3 or 4, 37%), and neutropenia (58%; grade 3 or 4, 31%) were reported in patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134). The median times to onset for thrombocytopenia and grade 3 or higher neutropenia were 28 and 33 days, respectively.
Bleeding was reported in patients who received selinexor in clinical studies, some cases were associated with thrombocytopenia. Monitor patients for signs and symptoms of bleeding. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop bleeding. Bleeding associated with thrombocytopenia (23%) and epistaxis (12%; grade 3 or 4, 0.5%) occurred in patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202); fatal bleeding occurred in less than 1% of patients. Bleeding associated with thrombocytopenia occurred in 16% (grade 3 or 4, 2%; grade 5, 2%) of patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial. Bleeding was reported in 10% (grade 3 or 4, 0.7%) of patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134). The term bleeding included injection-site hematoma, subdural hematoma, hematuria, epistaxis, rectal hemorrhage, upper GI bleeding, and corneal/ocular hemorrhage.
Infection was reported in 49% to 69% of patients who received selinexor therapy in clinical studies; some cases were fatal. Most infections were not associated with severe neutropenia. Monitor patients for signs and symptoms of infection; evaluate and treat promptly. Infection (52%; grade 3 or 4, 21%; grade 5, 4%) including upper respiratory tract infection (21%; grade 3 or 4, 3%), pneumonia including atypical pneumonia (13%; grade 3 or higher, 9%), and sepsis (6%) occurred in patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202). The median times to onset of pneumonia and sepsis were 54 and 42 days, respectively. Infection (69%; grade 3 or 4, 28.9%; grade 5, 3.1%) including upper respiratory infection (29%; grade 3 or 4, 3.6%), pneumonia (grade 3 or 4, 14%), and sepsis (grade 3 or 4, 4.1%) occurred in patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial. Infection (49%; grade 3 or 4, 20.5%; grade 5, 4.5%) including upper respiratory tract infection (17%; grade 3 or 4, 1.5%), pneumonia (10%; grade 3 or 4, 6%), urinary tract infection (10%; grade 3 or 4, 3%), sepsis (6%), and herpes virus infection (3%) were reported in patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134). The median time to onset of grade 3 or higher infection was 42 days. In these studies, the term upper respiratory tract infection includes pharyngitis, nasopharyngitis, bronchitis, bronchiolitis, respiratory syncytial virus infection, influenza/parainfluenza virus infection, rhinitis, rhinovirus infection, and adenovirus infection.
Fatigue was reported in 59% to 73% of patients who received selinexor therapy in clinical studies. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop fatigue. Fatigue occurred in 73% (grade 3 or 4, 22%) of patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202). Fatigue occurred in 59% (grade 3 or 4, 21%) of patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial. Fatigue were reported in 63% (grade 3 or 4, 15%) of patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134). The term fatigue included asthenia.
Gastrointestinal (GI) toxicity including nausea (50% to 72%), vomiting (21% to 41%), diarrhea (27% to 44%), constipation (29% or less), and dehydration (14% or less) were reported in patients who received selinexor therapy in clinical studies. Evaluate serum electrolyte levels at baseline and throughout treatment; monitor more frequently during the first 3 months of treatment. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop GI toxicity. Administer a 5-HT3 antagonist and/or other antiemetic agents prior to and during selinexor therapy; additional antiemetic medications may be required. Standard antidiarrheal agents may be given in patients who develop diarrhea. Administer IV fluids to prevent dehydration and replace electrolytes as clinically indicated. Nausea (72%; grade 3 or 4, 9%), diarrhea (44%; grade 3 or 4, 6%), vomiting (41%; grade 3 or 4, 3.5%), constipation (25%; grade 3 or 4, 1.5%), and dehydration (14%; grade 3 or 4, 3.5%) were reported in patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202). The median times to onset of nausea, vomiting, and diarrhea were 3, 5, and 15 days, respectively. Nausea (50%; grade 3, 8%), diarrhea (32%; grade 3, 6%), and vomiting (21%; grade 3, 4.1%) were reported in patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial. The median time to first onset of nausea, vomiting, and diarrhea was 6, 8, and 50 days, respectively. GI toxicity (80%; grade 3 or 4, 13%) including nausea (57%; grade 3 or 4, 6%), diarrhea (37%; grade 3 or 4, 3%), constipation (29%), vomiting (28%; grade 3 or 4, 1.5%), and abdominal pain (10%) occurred in patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134); dehydration was reported in 7% of patients. The term diarrhea included gastroenteritis. The median time to first onset of nausea, vomiting, and diarrhea was 3, 7, and 12 days, respectively.
Decreased appetite/anorexia (35% to 53%) and weight loss (26% to 47%) were reported in patients who received selinexor therapy in clinical studies. Evaluate body weight, nutritional status, and volume status levels at baseline and throughout treatment; monitor more frequently during the first 3 months of treatment. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop anorexia or weight loss. Provide nutritional support as clinically indicated. Anorexia (53%; grade 3 or 4, 4.5%) and weight loss (47%; grade 3 or 4, 0.5%) occurred in patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202). The median times to onset of anorexia and weight loss were 8 and 15 days, respectively. Anorexia (35%; grade 3, 3.6%) and weight loss (26%; grade 3 or 4, 2.1%) were reported in patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial. The median time to first onset of anorexia and weight loss was 35 and 58 days, respectively. Anorexia (37%; grade 3 or 4, 3.7%) and weight loss (30%) were reported in patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134). The term decreased appetite include hypophagia.
Hyponatremia/decreased sodium level was reported in 39% to 62% of patients who received selinexor therapy in clinical studies. Obtain serum electrolytes including sodium levels at baseline and throughout treatment; monitor electrolytes more frequently during the first 3 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose greater than 150 mg/dL) and high serum paraprotein levels. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop hyponatremia (sodium level of 130 mmol/L or less). Assess hydration status and manage hyponatremia per clinical guidelines (e.g., IV saline and/or salt tablets) including a dietary review. Hyponatremia (39%; grade 3 or 4, 22%) and hypokalemia (12%; grade 3 or 4, 3.5%) occurred in patients with relapsed or refractory multiple myeloma who received selinexor plus dexamethasone in clinical trials (n = 202). The median time to onset of hyponatremia was 8 days. Electrolyte abnormalities including worsening hyponatremia (58%; grade 3 or 4, 14%), hypophosphatemia/decreased phosphate level (61%; grade 3 or 4, 23%), hypomagnesemia/decreased magnesium level (27%; grade 3 or 4, less than 1%), hypocalcemia/decreased calcium level (55%; grade 3 or 4, 2.1%), hyperkalemia/increased potassium level (18%; grade 3 or 4, 4.1%), and hypokalemia/decreased potassium level (27%; grade 3 or 4, 6%) occurred in patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial. Electrolyte abnormalities including worsening hyponatremia (62%; grade 3 or 4, 16%), hypophosphatemia (34%; grade 3 or 4, 11%), hypomagnesemia (30%; grade 3 or 4, 2.6%), hypocalcemia (30%; grade 3 or 4, 0.9%), hyperkalemia (26%; grade 3 or 4, 3.9%), and hypokalemia (23%; grade 3 or 4, 7%) were reported in patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134). In approximately 63% of cases, hyponatremia occurred in the context of gastrointestinal toxicity such as nausea, vomiting, diarrhea, dehydration, and anorexia.
Hyperglycemia/decreased glucose level was reported in 15% and 62% of patients who received selinexor therapy in clinical studies. Hyperglycemia occurred in 15% (grade 3 or 4, 7%) of patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202). Hyperglycemia occurred in 62% (grade 3 or 4, 3.8%) of patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial. Hyperglycemia was reported in 57% (grade 3 or 4, 5%) of patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134).
Respiratory adverse events including dyspnea (10% and 24%) and cough (16% and 18%) were reported in patients who received selinexor therapy in 2 clinical studies. Dyspnea (24%; grade 3 or higher, 3.5%) and cough (16%) occurred in patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202). Dyspnea (10%; grade 3 or higher, 1.5%) and cough (18%) were reported in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134).
Neurotoxicity was reported in 25% to 30% of patients who received selinexor therapy in clinical studies. Institute fall precautions as appropriate. Ensure patients have adequate hydration and hemoglobin levels during therapy. Review patient medication and history lists to identify other factors that may also cause dizziness or mental status changes; concomitant use may increase the risk of neurotoxicity. Neurotoxicity (30%; grade 3 or 4, 9%) including mental status changes (16%; grade 3 or 4, 7%), dizziness (15%), and headache (10%) occurred in patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202). The median time to onset of neurotoxicity was 15 days. Neurotoxicity (26%; grade 3 or 4, 3.6%) including dizziness (12%; grade 3 or 4, less than 1%), syncope (3.6%), mental status changes (9%), depressed level of consciousness, vertigo, and amnesia occurred in patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial; peripheral neuropathy was reported in 32% (grade 3 or 4, 4.6%) of patients who received selinexor, bortezomib, and dexamethasone. The median time to the first neurotoxic event was 29 days. Neurotoxicity (25%; grade 3 or 4, 6%) including dizziness (16%; grade 3 or 4, 0.7%), mental status changes (11%; grade 3 or 4, 3.7%), and sensory peripheral neuropathy (10%), headache (4.5%), and syncope (2.2%) were reported in patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134); falls were reported in 8% of patients. The median time to the first neurotoxic event was 28 days. The term mental status changes included confusion, delirium, amnesia, cognitive disorder/impaired cognition, hallucinations, somnolence/drowsiness, depressed level of consciousness, and memory impairment. The term dizziness included vertigo. The term peripheral neuropathy included sensory disturbance, paresthesias, polyneuropathy, toxic neuropathy, and neuralgia.
Insomnia occurred in 15% (grade 3 or 4, 2%) of patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202).
Fever was reported in 15% and 22% of patients who received selinexor therapy in clinical studies. Fever occurred in 16% (grade 3 or 4, 0.5%) of patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202). Fever occurred in 15% (grade 3 or 4, 1.5%) of patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial. Fever was reported in 22% (grade 3 or 4, 4.5%) of patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134).
Nephrotoxicity, specifically increased creatinine level, has been reported in 14% to 47% patients who received selinexor therapy in clinical studies. Obtain renal function tests (e.g., serum creatinine/BUN levels) at baseline and throughout treatment as clinically indicated; monitor renal function tests more frequently during the first 3 months of treatment. Increased creatinine level occurred in 14% (grade 3 or 4, 2%) of patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202). Increased serum creatinine level (28%; grade 3 or 4, 3.6%) and increased BUN level (41%; grade 3 or 4, 5%) occurred in patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial. Increased creatinine level was reported in 47% (grade 3 or 4, 3.9%) of patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134).
Dysgeusia occurred in 11% of patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202). Taste disorder were reported in 13% of patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134). The term taste disorder included dysgeusia and ageusia.
Blurred vision was reported in 10% to 13% of patients who received selinexor therapy in clinical studies. Perform an ophthalmologic evaluation in patients who develop grade 2 or higher ocular toxicity, excluding cataracts; provide supportive care as applicable. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop ocular toxicity. The treatment of cataracts usually requires surgical removal of the cataract. Blurred vision occurred in 10% (grade 3 or 4 0.5%) of patients with relapsed or refractory multiple myeloma who received selinexor 80 mg PO twice weekly plus dexamethasone in a nonrandomized trial (n = 202). Blurred vision (13%; grade 3 or 4, less than 1%) and cataracts (22%; grade 3 or 4, 9%) were reported in patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial. The median time to new onset of or worsening of cataract was 228 and 237 days, respectively. Blurred vision (11%; grade 3 or 4, 0.7%) and cataracts (3.7%) were reported in patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134). The term blurred vision included reduced visual acuity and visual impairment.
Edema was reported in 17% (grade 3 or 4, 2.2%) of patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134).The term edema include swelling, face swelling, peripheral edema, peripheral swelling, and acute pulmonary edema.
Musculoskeletal pain (15%; grade 3 or 4, 2.2%) and worsening increased creatine kinase (CK) level (3.7%) were reported in patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134). However, increased CK level was not associated with reports of myopathy or myalgia. The term musculoskeletal pain included back pain, musculoskeletal chest pain, neck pain, extremity pain, and bone pain.
Hypotension (13%; grade 3 or 4, 3%) and heart failure (3%) were reported in patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134).
Hepatotoxicity has been reported with selinexor therapy. Obtain liver function tests (LFTs) at baseline and throughout treatment as clinically indicated; monitor LFTs more frequently during the first 3 months of treatment. Elevated hepatic enzymes including increased AST (24%; grade 3 or 4, 1.5%), ALT (33%; grade 3 or 4, 3.1%), and alkaline phosphatase (12%) levels, hypoalbuminemia (27%; grade 3 or 4, less than 1%), and hyperbilirubinemia/increased bilirubin level (16%; grade 3 or 4, 1%) occurred in patients with relapsed or refractory multiple myeloma who received selinexor 100 mg PO once weekly plus bortezomib and dexamethasone (n = 195) in a randomized trial. Increased AST (24%; grade 3 or 4, 3.1%) and ALT (29%; grade 3 or 4, 0.8%) levels, hypoalbuminemia (25%), and hyperbilirubinemia (16%; grade 3 or 4, 1.6%) were reported in patients with relapsed or refractory diffuse large B-cell lymphoma who received selinexor 60 mg PO twice weekly in a nonrandomized trial (n = 134).
Severe hematologic toxicity (e.g., anemia, thrombocytopenia, neutropenia) and bleeding have been reported with selinexor therapy. Obtain complete blood counts (CBC) with differential at baseline and throughout treatment; monitor CBCs more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of bleeding; evaluate promptly. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop severe myelosuppression or bleeding. Administer blood or platelet transfusions, granulocyte-colony stimulating factors, or other medical treatment as clinically indicated.
Severe gastrointestinal (GI) toxicity (e.g., nausea/vomiting, diarrhea, and anorexia) and weight loss have been reported with selinexor therapy. Evaluate body weight, nutritional status, volume status, and serum electrolyte levels at baseline and throughout treatment; monitor more frequently during the first 3 months of treatment. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop GI toxicity or weight loss. Administer a 5-HT3 antagonist and/or other antiemetic agents prior to and during selinexor therapy; additional antiemetic medications may be required. Standard antidiarrheal agents may be given in patients who develop diarrhea. Administer IV fluids to prevent dehydration, replace electrolytes, and nutritional support as clinically indicated.
Severe hyponatremia has been reported with selinexor therapy. Obtain serum sodium levels at baseline and throughout treatment; monitor sodium levels more frequently during the first 2 months of treatment. Correct sodium levels for concurrent hyperglycemia (serum glucose greater than 150 mg/dL) and high serum paraprotein levels. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop hyponatremia (sodium level of 130 mmol/L or less). Assess hydration status and manage hyponatremia per clinical guidelines (e.g., IV saline and/or salt tablets) including a dietary review.
Infection (e.g., pneumonia and sepsis) has been reported with selinexor therapy; some cases were fatal. Most infections are not associated with severe neutropenia; some are atypical infections (e.g., fungal infection, herpes infection). Monitor patients for signs and symptoms of infection; evaluate and treat promptly.
Severe neurotoxicity (e.g., dizziness, syncope, and mental status changes) has been reported with selinexor therapy. Institute fall precautions as appropriate. Ensure patients have adequate hydration and hemoglobin levels during therapy. Review patient medication and history lists to identify other factors that may also cause dizziness or mental status changes; concomitant use may increase the risk of neurotoxicity. Patients should avoid driving or operating machinery until the neurotoxicity resolves.
Geriatric patients aged 75 years and older with multiple myeloma who received selinexor and dexamethasone experienced a higher incidence of serious (70% vs. 58%) and fatal (17% vs. 9%) adverse reactions compared with younger patients. Geriatric patients aged 65 years and older with multiple myeloma who received selinexor, bortezomib, and dexamethasone experienced a higher incidence of serious adverse reactions (56% vs. 47%) compared with younger patients.
Ocular toxicity has been reported with selinexor therapy, including new onset or exacerbation of cataracts. Perform an ophthalmologic evaluation in patients who develop grade 2 or higher ocular toxicity, excluding cataracts; provide supportive care as applicable. Therapy interruption, a dosage reduction, or discontinuation may be necessary in patients who develop ocular toxicity. The treatment of cataracts usually requires ocular surgery to remove the cataract.
Hepatotoxicity has been reported with selinexor therapy. Obtain liver function tests (LFTs) at baseline and throughout treatment as clinically indicated; monitor LFTs more frequently during the first 3 months of treatment.
Nephrotoxicity has been reported in patients who received selinexor therapy. Obtain renal function tests (e.g., serum creatinine/BUN levels) at baseline and throughout treatment as clinically indicated; monitor renal function tests more frequently during the first 3 months of treatment.
Selinexor may cause fetal harm if administered during pregnancy based on its mechanism of action and data from animal studies. Females of reproductive potential should be advised to avoid becoming pregnant while receiving selinexor. If a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus. In a study in pregnant rats, embryo-fetal toxicities including incomplete or delayed ossification, skeletal variations, reduced fetal weight, microphthalmia, fetal edema, malpositioned kidney, and persistent truncus arteriosus were observed at selinexor doses that resulted in maternal exposures that were less than the human exposure at the recommended dose.
Counsel patients about the reproductive risk and contraception requirements during selinexor treatment. Pregnancy testing should be performed prior to starting selinexor in female patients of reproductive potential. These patients should use effective contraception and avoid pregnancy during and for 1 week after selinexor therapy. Women who become pregnant while receiving selinexor should be apprised of the potential hazard to the fetus. Additionally, male patients with a female partner of reproductive potential should use effective contraception during therapy and for 1 week after therapy due to the risk of male-mediated teratogenicity. Based on animal studies, selinexor may cause infertility in males and females.
No information is available regarding the presence of selinexor or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Due to the potential for serious adverse reactions in the nursing child, breast-feeding is not recommended during therapy or for 1 week after the last selinexor dose.
For the treatment of multiple myeloma:
NOTE: The FDA has designated selinexor as an orphan drug for the treatment of multiple myeloma.
-for the treatment of multiple myeloma in patients who have received at least 4 prior therapies and who are refractory to at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody, in combination with dexamethasone:
Oral dosage:
Adults: 80 mg orally in combination with dexamethasone 20 mg orally on days 1 and 3 of each week. Repeat weekly until disease progression. Maintain adequate fluid and caloric intake throughout treatment. Consider intravenous hydration for patients at risk of dehydration. Administer a 5-HT3 antagonist and other anti-nausea agents prior to and during treatment. Therapy interruption, dose reduction, or discontinuation may be necessary for treatment-related toxicity. Treatment with selinexor plus dexamethasone (median duration of therapy, 9 weeks; range 1 to 60 weeks) resulted in an overall response rate of 26% in a multicenter, phase 2b trial (n = 122; the STORM trial). Of note, a partial response was achieved in 2 patients who had relapsed disease following CART-T therapy. In this trial, the median duration of response was 4.4 months, the median progression-free survival time was 3.7 months, and the median overall survival time was 8.6 months. Patients (median age, 65.2 years; range, 40 to 86 years) had received a median of 7 prior regimens (range, 3 to 18 regimens) and were refractory to at least 1 proteasome inhibitor, 1 immunomodulatory drug, and daratumumab; 84% of patients had previously received a transplant.
-for the treatment of multiple myeloma in patients who have received at least 1 prior therapy, in combination with bortezomib and dexamethasone:
Oral dosage:
Adults: 100 mg orally on day 1 once weekly in combination with bortezomib 1.3 mg/m2 subcutaneously on day 1 once weekly for 4 weeks followed by 1 week off and dexamethasone 20 mg orally on days 1 and 2 of each week; repeat cycles until disease progression. Maintain adequate fluid and caloric intake throughout treatment. Consider intravenous hydration for patients at risk of dehydration. Administer a 5-HT3 antagonist and other anti-nausea agents prior to and during treatment. Therapy interruption, dose reduction, or discontinuation may be necessary for treatment-related toxicity. Treatment with a once-weekly regimen of selinexor plus bortezomib, and dexamethasone (XVd regimen) led to a significantly improved median progression-free survival time compared with bortezomib and dexamethasone (13.93 months vs. 9.46 months; hazard ratio (HR) = 0.7; 95% CI, 0.53 to 0.93) in a randomized, phase 3 trial (n = 402; the Boston trial). At a median follow-up of 17.3 months, the median overall survival (OS) time was not significantly improved in the XVd arm (HR = 0.84; 95% CI, 0.57 to 1.23); however, OS data was not mature at the time of this analysis. Patients (median age, 67 years) in this trial had received a median of 2 prior regimens (range, 1 to 2 regimens) and approximately 70% of patients had received prior bortezomib therapy; 35% of patients had previously received a stem-cell transplant.
For the treatment of non-Hodgkin's lymphoma (NHL):
NOTE: The FDA has designated selinexor as an orphan drug for the treatment of diffuse large B-cell lymphoma.
-for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 prior lines of systemic therapy:
Oral dosage:
Adults: 60 mg orally on days 1 and 3 of each week. Repeat weekly until disease progression. Maintain adequate fluid and caloric intake throughout treatment. Consider intravenous hydration for patients at risk of dehydration. Administer a 5-HT3 antagonist and other anti-nausea agents prior to and during treatment. Therapy interruption, dose reduction, or discontinuation may be necessary for treatment-related toxicity. Treatment with selinexor (median duration of therapy, 2.1 months; range 1 week to 3.7 years) resulted in an overall response rate of 29% (complete response rate, 13%) in patients with relapsed or refractory DLBCL in a multicenter, phase 2b trial (n = 134; the SADAL trial). The response rates maintained at 3, 6, and 12 months were 56%, 38%, and 15%, respectively. Patients (median age, 67 years; range, 35 to 91 years) had received a median of 2 prior regimens (range, 1 to 5 regimens); 30% of patients had previously received an autologous stem-cell transplant.
Therapeutic Drug Monitoring:
Dosage Guidance for Treatment-Related Toxicity:
Multiple Myeloma
For starting dose of 80 mg twice weekly:
First reduction: 100 mg PO once weekly.
Second reduction: 80 mg PO once weekly.
Third reduction: 60 mg PO once weekly.
Fourth reduction: Permanently discontinue treatment.
For starting dose of 100 mg once weekly:
First reduction: 80mg PO once weekly.
Second reduction: 60 mg PO once weekly.
Third reduction: 40 mg PO once weekly.
Fourth reduction: Permanently discontinue treatment.
Diffuse Large B-cell Lymphoma (DLBCL)
First reduction: 40 mg PO on days 1 and 3 weekly.
Second reduction: 60 mg PO once weekly.
Third reduction: 40 mg PO once weekly.
Fourth reduction: Permanently discontinue treatment.
Hematologic Toxicity
Multiple Myeloma
Thrombocytopenia
Platelet count of 25,000 to less than 75,000 cells/microliter (mcL): Reduce the selinexor dose by 1 dose level.
Platelet count of 25,000 to less than 75,000 cells/mcL with concurrent bleeding: Interrupt selinexor therapy. After bleeding has resolved, restart selinexor therapy at 1 dose level lower and administer platelet transfusions per clinical guidelines.
Platelet count of less than 25,000 cells/mcL: Interrupt selinexor therapy. Monitor until platelet count returns to at least 50,000 cells/mcL. Restart selinexor therapy at 1 dose level lower.
Neutropenia
Absolute neutrophil count (ANC) of 500 to 1,000 cells/mcL without fever: Reduce the selinexor dose by 1 dose level.
ANC less than 500 cells/mcL OR febrile neutropenia: Interrupt selinexor therapy. Monitor until neutrophil counts return to 1,000 cells/mcL or higher. Restart selinexor therapy at 1 dose level lower.
Anemia
Hemoglobin level less than 8 g/dL: Reduce the selinexor dose by 1 dose level. Administer blood transfusions per clinical guidelines.
Life-threatening consequences: Interrupt selinexor therapy. Monitor until hemoglobin levels return to 8 g/dL or higher. Restart selinexor therapy at 1 dose level lower. Administer blood transfusions per clinical guidelines.
DLBCL
Thrombocytopenia
Platelet count of 50,000 to less than 75,000 cells/microliter (mcL): Skip 1 dose of selinexor. Resume selinexor therapy at the same dose level.
First occurrence of platelet count of 25,000 to less than 50,000 cells/mcL WITHOUT bleeding: Interrupt selinexor therapy. Monitor until platelet count returns to at least 50,000 cells/mcL. Restart selinexor therapy at 1 dose level lower.
Platelet count of 25,000 to less than 50,000 cells/mcL WITH concurrent bleeding: Interrupt selinexor therapy. Monitor until platelet count returns to at least 50,000 cells/mcL. After bleeding has resolved, restart selinexor therapy at 1 dose level lower and administer platelet transfusions per clinical guidelines.
Platelet count of less than 25,000 cells/mcL: Interrupt selinexor therapy. Monitor until platelet count returns to at least 50,000 cells/mcL. Restart selinexor therapy at 1 dose level lower and administer platelet transfusions per clinical guidelines.
Neutropenia
First occurrence of ANC of 500 to 1,000 cells/mcL without fever: Interrupt selinexor therapy. Monitor until neutrophil counts return to 1,000 cells/mcL or higher. Resume selinexor therapy at the same dose level.
Second and subsequent occurrences of ANC of 500 to 1,000 cells/mcL without fever: Interrupt selinexor therapy. Monitor until neutrophil counts return to 1,000 cells/mcL or higher. Reduce the selinexor dose by 1 dose level and administer growth factors per clinical guidelines.
ANC less than 500 cells/mcL OR febrile neutropenia: Interrupt selinexor therapy. Monitor until neutrophil counts return to 1,000 cells/mcL or higher. Restart selinexor therapy at 1 dose level lower and administer growth factors per clinical guidelines.
Anemia
Hemoglobin level less than 8 g/dL: Reduce the selinexor dose by 1 dose level. Administer blood transfusions per clinical guidelines.
Life-threatening consequences (urgent intervention indicated): Interrupt selinexor therapy. Monitor until hemoglobin levels return to 8 g/dL or higher. Restart selinexor therapy at 1 dose level lower. Administer blood transfusions per clinical guidelines.
Non-Hematologic Toxicity (for Multiple Myeloma and DLBCL)
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): Maintain current selinexor dosage and initiate additional anti-nausea medications.
Grade 3 nausea (inadequate oral caloric or fluid intake) OR grade 3 or higher vomiting (6 or more episodes per day): Interrupt selinexor therapy. Monitor until nausea or vomiting has resolved to Grade 2 or lower or baseline. Initiate additional anti-nausea medications. Restart selinexor therapy at 1 dose level lower.
Diarrhea
First occurrence of grade 2 diarrhea (increase of 4 to 6 stools per day over baseline): Maintain selinexor dosage and institute supportive care.
Second and subsequent occurrences of grade 2 diarrhea (increase of 4 to 6 stools per day over baseline): Reduce the selinexor dose by 1 dose level and institute supportive care.
Grade 3 or higher diarrhea (increase of 7 stools or more per day over baseline; hospitalization indicated): Interrupt selinexor therapy and institute supportive care. Monitor until diarrhea resolves to grade 2 or lower. Restart selinexor therapy at 1 dose level lower.
Weight loss and anorexia
Weight loss of 10% to less than 20% OR anorexia associated with significant weight loss or malnutrition: Interrupt selinexor therapy and institute supportive care. Monitor until weight returns to more than 90% of baseline weight. Restart selinexor therapy at 1 dose level lower.
Hyponatremia
Sodium level of 130 mmol/L or less: Interrupt selinexor therapy, evaluate, and provide supportive care. Monitor until sodium levels return to greater than 130 mmol/L. Restart selinexor therapy at 1 dose level lower.
Fatigue
Grade 2 fatigue lasting greater than 7 days OR grade 3 fatigue: Interrupt selinexor therapy. Monitor until fatigue resolves to grade 1 or baseline. Restart selinexor therapy at 1 dose level lower.
Ocular Toxicity
Grade 2 toxicity, excluding cataracts: Interrupt selinexor therapy and provide supportive care. Perform an ophthalmologic evaluation. Monitor until ocular symptoms resolve to grade 1 or baseline. Restart selinexor therapy at 1 dose level lower.
Grade 3 or 4 toxicity, excluding cataracts: Permanently discontinue treatment. Perform an ophthalmologic evaluation.
Other non-hematologic adverse reactions
Grade 3 or 4 toxicity: Interrupt selinexor therapy. Monitor toxicity until resolved to grade 2 or lower. Restart selinexor therapy at 1 dose level lower.
Maximum Dosage Limits:
-Adults
Diffuse large B-cell lymphoma: 60 mg PO twice weekly on days 1 and 3.
Multiple myeloma: 80 mg PO twice weekly on days 1 and 3 OR 100 mg PO once weekly on day 1.
-Geriatric
Diffuse large B-cell lymphoma: 60 mg PO twice weekly on days 1 and 3.
Multiple myeloma: 80 mg PO twice weekly on days 1 and 3 OR 100 mg PO once weekly on day 1.
-Adolescents
Safety and efficacy not established.
-Children
Safety and efficacy not established.
-Infants
Safety and efficacy not established.
-Neonates
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Selinexor is a reversible nuclear export inhibitor that works by blocking tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins resulting in the accumulation of TSPs in the nucleus, reductions in several oncoproteins, such as c-myc and cyclin D1, cell cycle arrest, and apoptosis of cancer cells. It has shown activity in multiple myeloma cell lines in vitro and anti-tumor activity in murine xenograft models of multiple myeloma and diffuse large B-cell lymphoma. Exportin-1 (XPO1) is a protein transport receptor that allows for the nucleus to cytoplasm translocation of regulatory proteins, including TSPs and oncoproteins. Dysregulation (e.g., upregulation of XPO1) in this transport process may lead to tumor cell proliferation. Overexpression of XPO1 has been observed in solid tumors and hematologic malignancies including multiple myeloma and is associated with poor prognosis and drug resistance. In multiple myeloma cells, XPO1 inhibition results in apoptosis via p53 and caspases activation, nuclear localization of TSPs, downregulation of c-myc and cell cycle regulatory genes, and promotion of G1/S cell cycle arrest.
Selinexor is administered orally. It is 95% bound to plasma proteins and the apparent volume of distribution is 133 L. Following a single dose of selinexor in cancer patients, the mean half-life was 6 to 8 hours and the apparent total clearance was 18.6 L/hour. Selinexor is metabolized in the liver via CYP3A4, multiple UDP-glucuronosyltransferases (UGTs), and glutathione S transferases (GSTs).
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4
Selinexor is a substrate of CYP3A4. In vitro, it is a substrate of multiple UGTs and GSTs and an inhibitor of OATP1B. The pharmacokinetic parameters of selinexor were not significantly impacted when selinexor was coadministered with up to 1,000 mg/day of clarithromycin (a strong CYP3A4 inhibitor) or acetaminophen.
-Route-Specific Pharmacokinetics
Oral Route
The selinexor AUC and Cmax values increased proportionately over the dose range of 3 to 85 mg/m2 and no significant accumulation occurred. Following a single 60-mg dose of selinexor, the mean AUC and Cmax values were 4,096 (+/- 1,185) nanograms (ng)/mL x hour and 442 (+/- 188) ng/mL, respectively. Following a single 80-mg dose of selinexor, the mean AUC and Cmax values were 5,386 (+/- 1,116) ng/mL x hour and 680 (+/- 124) ng/mL, respectively. Following a single 100-mg dose of selinexor, the mean AUC and Cmax values were 6,998 (+/- 818) ng/mL x hour and 693 (+/- 201) ng/mL, respectively. The time to maximum plasma concentration (Tmax) is 4 hours post-dose.
Effects of food: Compared with the fasted state, the pharmacokinetic values were not clinically significantly affected when selinexor was administered with a high-fat meal (800 to 1,000 calories with about 50% of the total caloric content consisting of fat).
-Special Populations
Hepatic Impairment
Mild hepatic impairment had no clinically significant impact on the pharmacokinetic parameters of selinexor. It is not known if moderate or severe hepatic impairment has a clinically significant impact on the pharmacokinetic parameters of selinexor.
Renal Impairment
Mild to severe renal impairment (creatinine clearance (CrCl) of 15 to 89 mL/min) had no clinically significant impact on the pharmacokinetic parameters of selinexor. It is not known if end-stage renal disease (CrCl of less than 15 mL/min) or hemodialysis has a clinically significant impact on the pharmacokinetic parameters of selinexor.
Geriatric
Age (range, 18 to 94 years) had no clinically significant impact on the pharmacokinetic parameters of selinexor.
Gender Differences
Gender had no clinically significant impact on the pharmacokinetic parameters of selinexor.
Ethnic Differences
Ethnicity had no clinically significant impact on the pharmacokinetic parameters of selinexor.
Obesity
Weight (range, 36 to 168 kg) had no clinically significant impact on the pharmacokinetic parameters of selinexor.
Other
Tumor Type
Tumor type had no clinically significant impact on the pharmacokinetic parameters of selinexor.