Dear {{customText[ |##accTitle##]}} {{customText[##accLname##|##accFname##| ##accFname## ##accLname##]}},

Did you know that XPOVIO (selinexor) was the fastest growing brand in 3L MM in 2021?

*Based on Komodo claims analysis, comparing XPOVIO share in new patients vs. other major brands approved for 3L MM in FY 2021.¹

With increased use of triplets, patients often progress on PIs, IMiDs, and anti–CD38 mABs by 2–3 lines of therapy.² For such patients, including those with prior anti-CD38 mAB exposure, consider a mechanistic switch with XPOVIO — the first and only FDA approved XPO1 inhibitor.³

Reasons to consider prescribing XPOVIO for patients with MM after at least 1 prior therapy:

Different MOA — XPO1 Inhibition:
XPOVIO (selinexor) reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1). XPO1 inhibition by selinexor leads to accumulation of TSPs in the nucleus and reductions in several oncoproteins, such as c‐myc and cyclin D1, cell cycle arrest, and apoptosis of cancer cells.³

NCCN Category 1 recommendation:
Oral, once weekly selinexor (XPOVIO^®) in combination with bortezomib and dexamethasone (XVd) is recommended by the NCCN Guidelines^® as a Category 1 therapeutic option in previously treated MM.⁴

*Category 1=Based upon high-level evidence, there is uniform National Comprehensive Cancer Network® (NCCN®) consensus that the intervention is appropriate. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Multiple Myeloma V.5.2022. ©National Comprehensive Cancer Network, Inc. 2022. All rights reserved. Accessed April 27, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Demonstrated efficacy:
XPOVIO (selinexor) reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and mRNAs of oncogenic proteins by blocking exportin 1 (XPO1). XPO1 inhibition by selinexor leads to accumulation of TSPs in the nucleus and reductions in several oncoproteins, such as c‐myc and cyclin D1, cell cycle arrest, and apoptosis of cancer cells.³

In the XPOVIO + Vd trial, XVd delivered a:

Safety Profile:
Fatal adverse reactions occurred in 6% of patients within 30 days of last treatment, including pneumonia (n=3), and sepsis (n=3).³

Warnings and precautions include: Thrombocytopenia, Neutropenia, Gastrointestinal toxicity, Hyponatremia, Serious infection, Neurological toxicity, Embryo‑fetal toxicity, and Cataract.³

Serious adverse reactions with XVd occurred in 52% of patients. Serious adverse reactions in greater than 3% of patients include pneumonia: 14%, sepsis: 4%, diarrhea: 4%, and vomiting: 4%.³

Most common adverse reactions with XVd greater than or equal to 20% with a difference between the arms of greater than 5% vs Vd were fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infections, weight decrease, cataract, and vomiting. Grade 3-4 laboratory abnormalities (≥10%) were thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia, and neutropenia.³

Permanent discontinuation of XPOVIO was seen in 19% of patients and dosage interruptions of XPOVIO due to an adverse reaction occurred in 83% of patients.³

Dose may be reduced to manage adverse reactions (ARs):
In the XVd arm of the clinical trial, the majority of the patients (126/195) had their XPOVIO dose reduced to manage adverse reactions.³

Efficacy was observed in patients on XVd with dose reduction:
In the Intent-to-treat (ITT) patient population of the XVd trial, the median PFS of XVd arm was 13.9 months (95% CI: 11.7, Not Reached) vs. 9.5 months (95% CI: 7.6, 10.8) in the Vd arm.³

In a post hoc analysis, patients in the XVd arm (N=195) who had their XPOVIO dose reduced (n=126) showed a mPFS of 16.6 months (95% CI: 12.9, NE)¹

Limitations of post hoc analysis, include:

Click below to learn more about XPOVIO + Vd in patients with MM

IMPORTANT SAFETY INFORMATION

Thrombocytopenia: XPOVIO can cause life‑threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma (MM) and developed or worsened in patients with DLBCL.

Thrombocytopenia is the leading cause of dosage modifications. Monitor platelet counts at baseline and throughout treatment. Monitor more frequently during the first 3 months of treatment. Monitor patients for signs and symptoms of bleeding. Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

Neutropenia: XPOVIO can cause life‑threatening neutropenia, potentially increasing the risk of infection.

Monitor more frequently during the first 3 months of treatment. Consider supportive measures, including antimicrobials and growth factors (e.g., G‑CSF). Interrupt, reduce dose, or permanently discontinue based on severity of adverse reaction.

Gastrointestinal Toxicity: XPOVIO can cause severe gastrointestinal toxicities in patients with MM and DLBCL.

Nausea/Vomiting/Diarrhea: Provide prophylactic antiemetics as needed.

Anorexia/Weight Loss: Monitor weight, nutritional status, and volume status at baseline and throughout treatment and provide nutritional support, fluids, and electrolyte repletion as clinically indicated.

Hyponatremia: XPOVIO can cause severe or life‑threatening hyponatremia.

Monitor sodium level at baseline and throughout treatment.

Serious Infection: XPOVIO can cause serious and fatal infections. Atypical infections reported after taking XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection.

Neurological Toxicity: XPOVIO can cause life‑threatening neurological toxicities.

Coadministration of XPOVIO with other products that cause dizziness or mental status changes may increase the risk of neurological toxicity.

Advise patients to refrain from driving and engaging in hazardous occupations or activities, until the neurological toxicity fully resolves. Institute fall precautions as appropriate.

Embryo‑Fetal Toxicity: XPOVIO can cause fetal harm when administered to a pregnant woman.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential and males with a female partner of reproductive potential to use effective contraception during treatment with XPOVIO and for 1 week after the last dose.

Cataracts: New onset or exacerbation of cataract has occurred during treatment with XPOVIO. In patients with MM who received XPOVIO 100mg once weekly, the incidence of new onset or worsening cataract requiring clinical intervention was reported.

ADVERSE REACTIONS

MM: The most common adverse reactions (ARs) (≥20%) in patients with multiple myeloma who received XVd were fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract, and vomiting.

In patients with MM, who received XVd, fatal ARs occurred in 6% of patients within 30 days of last treatment. Serious ARs occurred in 52% of patients. Treatment discontinuation rate due to ARs was 19%. The most frequent ARs requiring permanent discontinuation in >2% of patients included fatigue, nausea, thrombocytopenia, decreased appetite, peripheral neuropathy and vomiting. Adverse reactions led to XPOVIO dose interruption in 83% of patients and dose reduction in 64% of patients.

The most common ARs in ≥20% of patients with MM who received Xd were thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea, and upper respiratory tract infection.

In patients with MM, who received Xd fatal ARs occurred in 9% of patients. Serious ARs occurred in 58% of patients. Treatment discontinuation rate due to ARs was 27%. The most frequent ARs requiring permanent discontinuation in ≥4% of patients included fatigue, nausea, and thrombocytopenia. In patients with MM, adverse reactions led to XPOVIO dose interruption in 65% of patients and dose reduction in 53%.

DLBCL: The most common ARs, excluding laboratory abnormalities, in ≥20% of patients with DLBCL were fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‑4 laboratory abnormalities in ≥15% of patients included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. Grade 4 laboratory abnormalities in ≥5% were thrombocytopenia, lymphopenia, and neutropenia.

In patients with DLBCL, fatal ARs occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal AR was infection (4.5% of patients). Serious ARs occurred in 46% of patients; the most frequent serious AR was infection. Discontinuation due to ARs occurred in 17% of patients. In patients with DLBCL, adverse reactions led to XPOVIO dose interruption in 61% of patients and dose reduction in 49%, with 17% of all patients having 2 or more dose reductions.

USE IN SPECIFIC POPULATIONS

In MM, no overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥75 years old, with MM who received Xd, had a higher incidence of discontinuation due to an AR than younger patients, a higher incidence of serious ARs, and a higher incidence of fatal ARs.

The effect of end‑stage renal disease (CLCR <15 mL/min) or hemodialysis on XPOVIO pharmacokinetics is unknown.

Please see full Prescribing Information.

To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1-888-209-9326 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

© 2022 Karyopharm Therapeutics Inc.

{{customText[Best,|Best regards,|Thanks for your consideration,|Sincerely,|Thanks,|Thank you,|Cheers,]}}

{{userName}}{{User.KPTI_My_Credentials__c}}
Karyopharm Therapeutics, Inc.
{{User.MobilePhone}}
{{userEmailAddress}}

Reference: 1. Data on File, Karyopharm Therapeutics Inc. 2022. 2. Braunlin M et al. Leuk Lymphoma. 2021;62(2):377-386. 3. XPOVIO (selinexor) [prescribing information]. Newton, MA: Karyopharm Therapeutics Inc.; August 2021. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for Multiple Myeloma V.5.2022. © National Comprehensive Cancer Network, Inc. 2022.All rights reserved. Accessed April 29, 2022. To view the most recent and complete version of the guideline, go online to NCCN.org. 5. FDA website. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma. Accessed October 26, 2021. 6. FDA website. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-melphalan-flufenamide-relapsed-or-refractory-multiple-myeloma. Accessed October 26, 2021. 7. FDA website. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cell-based-gene-therapy-adult-patients-multiple-myeloma. Accessed October 26, 2021.

Colorado prescribers click here for Wholesale Acquisition Cost price disclosure pursuant to Colorado House Bill 19‑1131.