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{{customText[Dear|Hello|Hi]}} {{customText[ |##accTitle##]}} {{customText[##accLname##|##accFname##| ##accFname## ##accLname##]}},
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Thank you for your inquiry regarding XPOVIO® (selinexor). In response to your request, the following publication is enclosed:
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Guidance for Use and dosing of Selinexor in Multiple Myeloma in 2021: Consensus from International Myeloma Foundation Expert Roundtable
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XPOVIO is a nuclear export inhibitor indicated:
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In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.
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In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.
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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. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
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Information contained in this letter is being provided in response to an unsolicited request. Karyopharm Therapeutics, Inc. does not endorse the use of its products in any manner other than as described in the FDA‑approved prescribing information. The information provided herein is for your medical information purposes only and should not be regarded as a recommendation by Karyopharm Therapeutics, Inc. Any reference to data on file is confidential.
Please be advised that due to developments in the Federal reporting requirements, any costs associated with requests for reprints of scientific publications may be reported via the Open Payments (Physician Payments Sunshine Act) program.
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Please note the following corrections in the manuscript:
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In Table 1:
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- Data shown represents most frequent treatment emergent adverse events (TEAEs), not treatment related adverse events (TRAEs).
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- The correct sub column headers for the BOSTON TEAE column should be as follows (in order of appearance): SVd All Grades, SVd Grade 3/4, Vd All Grade, and Vd Grade 3/4.
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The investigational phase 2 dose for selinexor, pomalidomide, and dexamethasone (SPd) is selinexor 60mg weekly 4 out of 4 weeks, not 3 out of 4 weeks.
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In Table 2 of the manuscript, the supportive care and dose holding/reduction recommendations are different from those provided in the US FDA approved prescribing information for selinexor (XPOVIO®) as shown below:
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Table 1: |
XPOVIO Dosage Reduction Steps for Adverse Reactions |
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Multiple Myeloma
In Combination with Bortezomib and Dexamethasone (XVd) |
Multiple Myeloma
In Combination with Dexamethasone (Xd) |
Diffuse Large B‑Cell Lymphoma |
Recommended Starting Dosage |
100 mg once weekly |
80 mg Days 1 and 3 of each week (160 mg total per week) |
60 mg Days 1 and 3 of each week (120 mg total per week) |
First Reduction |
80 mg once weekly |
100 mg once weekly |
40 mg Days 1 and 3 of each week (80 mg total per week) |
Second Reduction |
60 mg once weekly |
80 mg once weekly |
60 mg once weekly |
Third Reduction |
40 mg once weekly |
60 mg once weekly |
40 mg once weekly |
Fourth Reduction |
Permanently discontinue |
Permanently discontinue |
Permanently discontinue |
Table 2: |
XPOVIO Dosage Modification Guidelines for Hematologic Adverse Reactions in Patients with Multiple Myeloma |
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Adverse Reaction |
Occurrence |
Action |
Thrombocytopenia [see Warning and Precautions (5.1)] |
Platelet count 25,000 to less than 75,000/mcL |
Any |
• Reduce XPOVIO by 1 dose level (see Table 1). |
Platelet count 25,000 to less than 75,000/mcL with concurrent bleeding |
Any |
• Interrupt XPOVIO.
• Restart XPOVIO at 1 dose level lower (see Table 1) after bleeding has resolved.
• Administer platelet transfusions per clinical guidelines. |
Platelet count less than 25,000/mcL |
Any |
• Interrupt XPOVIO.
• Monitor until platelet count returns to at least 50,000/mcL.
• Restart XPOVIO at 1 dose level lower (see Table 1). |
Neutropenia [see Warning and Precautions (5.2)] |
Absolute neutrophil count of 0.5 to 1 x 109/L without fever |
Any |
• Reduce XPOVIO by 1 dose level (see Table 1). |
Absolute neutrophil count less than 0.5 x 109/L OR febrile neutropenia |
Any |
• Interrupt XPOVIO.
• Monitor until neutrophil counts return to 1 x 109/L or higher.
• Restart XPOVIO at 1 dose level lower (see Table 1). |
Anemia |
Hemoglobin less than 8 g/dL |
Any |
• Reduce XPOVIO by 1 dose level (see Table 1).
• Administer blood transfusions per clinical guidelines. |
Life‑threatening consequences |
Any |
• Interrupt XPOVIO.
• Monitor hemoglobin until levels return to 8 g/dL or higher.
• Restart XPOVIO at 1 dose level lower (see Table 1).
• Administer blood transfusions per clinical guidelines. |
Table 4: |
XPOVIO Dosage Modification Guidelines for Non-Hematologic Adverse Reactions |
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Adverse Reaction |
Occurrence |
Action |
Nausea and Vomiting [see Warning and Precautions (5.3)] |
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 XPOVIO 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) |
Any |
• Interrupt XPOVIO.
• Monitor until nausea or vomiting has resolved to Grade 2 or lower or baseline.
• Initiate additional anti‑nausea medications.
• Restart XPOVIO at 1 dose level lower (see Table 1). |
Diarrhea [see Warning and Precautions (5.3)] |
Grade 2 (increase of 4 to 6 stools per day over baseline |
1st |
• Maintain XPOVIO and institute supportive care. |
2nd and subsequent |
• Reduce XPOVIO by 1 dose level (see Table 1).
• Institute supportive care. |
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Grade 3 or higher (increase of 7 stools or more per day over baseline; hospitalization indicated) |
Any |
• Interrupt XPOVIO and institute supportive care.
• Monitor until diarrhea resolves to Grade 2 or lower.
• Restart XPOVIO at 1 dose level lower (see Table 1). |
Weight Loss and Anorexia [see Warning and Precautions (5.3)] |
Weight loss of 10% to less than 20% OR Anorexia associated with significant weight loss or malnutrition |
Any |
• Interrupt XPOVIO and institute supportive care.
• Monitor until weight returns to more than 90% of baseline weight.
• Restart XPOVIO at 1 dose level lower (see Table 1). |
Hyponatremia [see Warning and Precautions (5.4)] |
Sodium level 130 mmol/L or less |
Any |
•Interrupt XPOVIO, evaluate, and provide supportive care.
• Monitor until sodium levels return to greater than 130 mmol/L.
• Restart XPOVIO at 1 dose level lower (see Table 1). |
Fatigue |
Grade 2 lasting greater than 7 days OR Grade 3 |
Any |
• Interrupt XPOVIO.
• Monitor until fatigue resolves to Grade 1 or baseline.
• Restart XPOVIO at 1 dose level lower (see Table 1). |
Ocular Toxicity [see Warning and Precautions (5.8)] |
Grade 2, excluding cataract |
Any |
• Perform ophthalmologic evaluation.
• Interrupt XPOVIO and provide supportive care.
• Monitor until ocular symptoms resolve to Grade 1 or baseline.
• Restart XPOVIO at 1 dose level lower (see Table 1). |
Grade ≥3, excluding cataract |
Any |
• Permanently discontinue XPOVIO.
• Perform ophthalmologic evaluation. |
Other Non‑Hematologic Adverse Reactions [see Warning and Precautions (5.6)] |
Grade 3 or 4 |
Any |
• Interrupt XPOVIO.
• Monitor until resolved to Grade 2 or lower; restart XPOVIO at 1 dose level lower (see Table 1). |
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For any further questions, please contact Karyopharm Medical Information at 888‑209‑9326 between the hours of 8:00 AM and 6:00 PM CT or via email at medicalinformation@karyopharm.com.
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Enclosure(s): Nooka AK, Costa LJ, Gasparetto CJ, et al. Guidance for Use and dosing of Selinexor in Multiple Myeloma in 2021: Consensus From International Myeloma Foundation Expert Roundtable. Clin Lymphoma Myeloma Leuk. 2022;22(7):e526-e531. doi:10.1016/j.clml.2022.01.014
Please see full XPOVIO Prescribing Information.
Karyopharm Therapeutics, Inc; 7/2022.
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