Adverse reactions and side effect management with XPOVIO + Vd

XPOVIO + Vd adverse reaction profile^1,2

ARs (≥10%) in patients with MM who received XPOVIO + Vd with a difference between arms of ≥5% compared to Vd¹

Weekly XVd (n=195)

Twice-weekly Vd (n=204)

Adverse reaction

All grades (%)

Grade 3 or 4 (%)

All grades (%)

Grade 3 or 4 (%)

Gastrointestinal

Nausea

Diarrhea

Vomiting

4.1

4.4

General Conditions

Fatigue^a

Pyrexia^a

1.5

Metabolism and Nutrition

Appetite decrease

3.6

Weight decrease

2.1

Nervous System

Peripheral neuropathy^b

4.6

Dizziness

3.9

Infections

Upper respiratory tract infections^c

3.6

1.5

Eye Disorders

Cataract

1.5

Vision blurred^d

^aFatigue includes fatigue and asthenia.

^bPeripheral neuropathy includes neuropathy peripheral, peripheral sensory neuropathy, polyneuropathy, peripheral sensorimotor neuropathy, toxic neuropathy, and peripheral motor neuropathy.

^cUpper respiratory tract infection includes upper respiratory infection, nasopharyngitis, pharyngitis, respiratory syncytial virus infection, respiratory tract infection, rhinitis, and viral upper respiratory tract infection.

^dVision blurred includes blurred vision, visual acuity reduced, and visual impairment.

The median treatment duration was 30 weeks (range, 1-120 weeks) in patients who received once-weekly XPOVIO + Vd as compared to 32 weeks (range, 1-122 weeks) in patients who received twice-weekly Vd¹

Adverse reactions

Serious ARs occurred in 52% of patients who received XPOVIO + Vd¹
Fatal ARs occurred in 6% of patients within 30 days of last treatment, including pneumonia (n=3) and sepsis (n=3)¹
Patients receiving XPOVIO + Vd experienced lower levels of grade ≥2 peripheral neuropathy (21% XPOVIO + Vd compared to 34% Vd)¹

Dosage reductions

Dosage reduction due to ARs occurred in 64% of patients¹

ARs requiring dose reductions in >5% of patients included thrombocytopenia (31%); decreased appetite (8%), nausea, fatigue, weight decreased (7% each); and asthenia (6%)¹

Dosage interruptions

Dosage interruptions due to ARs occurred in 83% of patients¹

The most frequent ARs requiring dosage interruption in >5% of patients included thrombocytopenia (33%), fatigue (13%), asthenia (12%), pneumonia (11%), upper respiratory tract infection (10%), decreased appetite (9%), neutropenia (8%), pyrexia (8%), nausea (7%), bronchitis (7%), diarrhea (6%), weight decreased (6%), and anemia (5%)¹

Dosage discontinuation

Permanent discontinuation of XPOVIO due to an AR occurred in 19% of patients¹

The most frequent ARs requiring permanent discontinuation in >2% of patients included fatigue (3.6%); nausea (3.1%); thrombocytopenia, decreased appetite, peripheral neuropathy, and vomiting (2.1% each)¹

In the XVd trial, nausea was transient and reversible²

With 92% of the cases resolved/resolving in the first month

Graph shows the percentage of patients experiencing nausea events in the XVd arm of the XVd trial in multiple myeloma

Before starting therapy and during treatment with XPOVIO, provide 2 prophylactic antiemetics^1,4^†

For grades 1 and 2 nausea: Maintain XPOVIO dose and add additional antiemetics
For grade 3 nausea: Interrupt XPOVIO, monitor nausea, add additional antiemetics, and restart XPOVIO at 1 dose level lower

^†One or both antiemetics may be tapered after 8 weeks of therapy.

For additional information, please see Section 2, “Dosage and Administration,” of the XPOVIO US Prescribing Information.

Select laboratory abnormalities

The following laboratory abnormalities (≥15%) worsened from baseline in patients with MM who received XVd¹

Weekly XVd

Twice-weekly Vd

Laboratory abnormality

All grades (%)

Grade 3 or 4 (%)

All grades (%)

Grade 3 or 4 (%)

Hematologic

Platelet count decrease

Lymphocyte count decrease

Hemoglobin decrease

51^a

Neutrophil count decrease

Chemistry

Glucose increase

3.8

4.1

Phosphate decrease

Sodium decrease

Calcium decrease

2.1

Blood urea nitrogen increase

Creatinine increase

3.6

1.5

Potassium decrease

3.5

Magnesium decrease

1.5

Potassium increase

4.1

2.5

Hepatic

ALT increase

3.1

Albumin decrease

AST increase

1.5

Bilirubin increase

ALP increase

Warnings and precautions include thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurologic toxicity, embryo-fetal toxicity, and cataract.

^aIncludes one fatal anemia.

The denominator used to calculate the rate varied from 91 to 201 based on the number of patients with at least 1 posttreatment value.

XPOVIO + Vd was not associated with serious organ toxicities of the cardiac, pulmonary, renal, or liver systems.³

XPOVIO dosage may be adjusted to help mitigate potential ARs¹*

XPOVIO dose reduction: incidence of duration-adjusted ARs⁵

Adverse reactions (%)

On or before first XPOVIO dose reduction (n=195)

After first XPOVIO dose reduction (n=126)

All grades

Grade ≥3

All grades

Grade ≥3

Thrombocytopenia

62.5

29.6

47.6

19.2

Nausea

31.6

3.9

7.3

2.7

Fatigue

28.1

4.1

9.9

2.7

Decreased appetite

21.5

1.6

6.4

0.4

Anemia

17.9

4.7

10.3

3.2

Diarrhea

12.9

2.0

5.2

0.7

Neutropenia

10.6

4.0

7.7

4.8

Weight decreased

9.0

0.6

5.9

0.7

*Duration-adjusted incidence of ARs is defined as the average number of events per 100 patients during a 4-week cycle.

See efficacy observed with dose reductions.

Next steps

Request a Rep

Ask questions and learn more about treating RRMM with XPOVIO.

Starting XPOVIO

Learn how to start patients on XPOVIO + Vd and how to adjust the dose for ARs if necessary.

Abbreviations: ALP, alkaline phosphatase; ALT, alanine transaminase; AR, adverse reaction; AST, aspartate aminotransferase; adverse reaction; MM, multiple myeloma; RRMM, relapsed or refractory multiple myeloma; Vd, bortezomib and dexamethasone; XVd, selinexor, bortezomib, and dexamethasone.

References: 1. XPOVIO (selinexor) [prescribing information]. Newton, MA. Karyopharm Therapeutics, Inc. 2. Data on file [1]. Karyopharm Therapeutics Inc. 2023. 3. Data on file [2]. Karyopharm Therapeutics Inc. 2023. 4. Gavriatopoulou M, Chari A, Chen C, et al. Integrated safety profile of selinexor in multiple myeloma: experience from 437 patients enrolled in clinical trials. Leukemia. 2020;34(9):2430-2440. doi:10.1038/s41375-020-0756-6 5. Jagannath S, Facon T, Badros AZ, et al. Clinical outcomes in patients with dose reduction of selinexor in combination with bortezomib, and dexamethasone (XVd) in previously treated multiple myeloma from the BOSTON study. Poster presented at: 63rd ASH Annual Meeting and Exposition; December 13, 2021; Atlanta, GA.

INDICATION

XPOVIO^® (selinexor) is a prescription medicine approved in combination with bortezomib and dexamethasone (XVd) to treat adult patients with multiple myeloma who have received at least one prior therapy.

IMPORTANT SAFETY INFORMATION

Thrombocytopenia: XPOVIO can cause life-threatening thrombocytopenia, potentially leading to hemorrhage. Thrombocytopenia was reported in patients with multiple myeloma.

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.

Nausea/Vomiting/Diarrhea: Provide prophylactic antiemetics or treatment 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. The incidence of new onset or worsening cataract requiring clinical intervention was reported.

ADVERSE REACTIONS

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.

Grade 3-4 laboratory abnormalities (≥10%) were thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia.

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.

USE IN SPECIFIC POPULATIONS

No overall difference in effectiveness of XPOVIO was observed in patients >65 years old when compared with younger patients. Patients ≥65 years old had a higher incidence of discontinuation due to an adverse reaction (AR) and a higher incidence of serious ARs than younger patients.

The effect of end-stage renal disease (CL_CR <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.

Adverse reactions and side effect management with XPOVIO + Vd

XPOVIO + Vd adverse reaction profile1,2

ARs (≥10%) in patients with MM who received XPOVIO + Vd with a difference between arms of ≥5% compared to Vd1

In the XVd trial, nausea was transient and reversible2

With 92% of the cases resolved/resolving in the first month

Select laboratory abnormalities

The following laboratory abnormalities (≥15%) worsened from baseline in patients with MM who received XVd1

XPOVIO dosage may be adjusted to help mitigate potential ARs1*

XPOVIO dose reduction: incidence of duration-adjusted ARs5

Request a Rep

Starting XPOVIO

INDICATION

IMPORTANT SAFETY INFORMATION

ADVERSE REACTIONS

USE IN SPECIFIC POPULATIONS

XPOVIO + Vd adverse reaction profile^1,2

ARs (≥10%) in patients with MM who received XPOVIO + Vd with a difference between arms of ≥5% compared to Vd¹

In the XVd trial, nausea was transient and reversible²

The following laboratory abnormalities (≥15%) worsened from baseline in patients with MM who received XVd¹

XPOVIO dosage may be adjusted to help mitigate potential ARs¹*

XPOVIO dose reduction: incidence of duration-adjusted ARs⁵