Selinexor for the treatment of multiple myeloma in adults

Selinexor Instructions

Product Name: LuciSelin

Manufacturer: Lucius Pharmaceuticals

Chinese name: Selinexor

English name: Selinexor

Drug approval number: 10 L 1027/23

 

【Summary】

Selinexor is an oral nuclear export inhibitor. In nonclinical studies, Selinexor reversibly inhibits nuclear export of tumor suppressor proteins (TSPs), growth regulators, and oncoprotein mRNAs by blocking Exportin 1 (XPO1). Selinexor inhibition of XPO1 leads to nuclear accumulation of TSPs, reduction of several oncoproteins such as c-myc and cyclinD1, cell cycle arrest, and apoptosis in cancer cells. Selinexor has shown pro-apoptotic activity in vitro in multiple myeloma cell lines and patient tumor samples, as well as in mouse xenograft models.

 

【Indications】

Selinexor is used to treat multiple myeloma in adults.

Selinexor in combination with low-dose dexamethasone for the treatment of refractory relapsed multiple myeloma (RRMM).

Selinexor may also be used in adults to treat certain types of diffuse large B-cell lymphoma.

 

【Specification】

20 mg/tablet, 4*8 tablets/box.

 

【Storage】

Store at 20°C to 25°C (68°C to 77°F); short-distance transport is permitted at a temperature range of 15 to 30°C (59–86°F).

 

【Usage and Dosage】

1. Selinexor is usually used only 2 days a week and is taken with dexamethasone. Please strictly follow your doctor's instructions and take the medicine at the same time on each medication day. Your doctor will decide when to take Selinexor and dexamethasone for treatment.

2. Take Selinexor with a full glass of water and swallow the medicine whole without crushing or chewing.

3. If you vomit soon after taking Selinexor, do not take another dose. Wait until the next dose time before taking the medicine.

4. Common adult dose for multiple myeloma: 80 mg orally on the 1st and 3rd day of each week until disease progression or unacceptable toxic effects occur.

5. The recommended starting dose of dexamethasone is 20 mg, taken together with Selinexor. 

【Adverse Reactions】

Allergic reaction: hives, difficulty breathing, swelling of your face, lips, tongue, or throat.

Selinexor may cause serious or fatal side effects. Some side effects may not occur until days or weeks after you start taking this medicine. Contact your doctor right away if you experience any of the following side effects:

Persistent severe nausea, vomiting, or diarrhea.

Loss of appetite, inability to eat and resulting in weight loss.

Confusion, dizziness, fainting, or changes in mental status.

Easy bruising, unusual bleeding, purple or red spots under the skin.

Signs of infection: Fever, chills, flu symptoms, cough with mucus, mouth and throat sores, fast heart rate, feeling short of breath, tingling or painful blistering rash on one side of the body.

Low red blood cell count (anemia): Pale skin, unusual tiredness, feeling dizzy, and cold hands and feet.

Low sodium levels: Headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady.

Common side effects of Selinexor may include:

Tiredness, anemia, bruising or bleeding, fever, infection, cold or flu symptoms, low sodium, nausea, vomiting, loss of appetite, diarrhea, constipation, weight loss, shortness of breath

【Taboo】

Contraindicated in patients with known severe hypersensitivity to Selinexor or its components.

 

【Notes】

Thrombocytopenia: Selinexor can cause thrombocytopenia, which can lead to potentially fatal bleeding. Thrombocytopenia was reported as an adverse reaction in 74% of patients, and severe (grade 3-4) thrombocytopenia was reported in 61% of patients treated with Selinexor. The median time to first adverse event was 22 days. Bleeding occurred in 23% of patients with thrombocytopenia, and clinically significant bleeding occurred in 5% of patients with thrombocytopenia.

Neutropenia: Selinexor can cause neutropenia, potentially increasing the risk of infection. Neutropenia was reported as an adverse reaction in 34% of patients, with severe (grade 3-4) neutropenia occurring in 21% of patients treated with selinexor. The median time to first occurrence of this adverse event was 25 days. Febrile neutropenia was reported in 3% of patients. Monitor neutrophil counts at baseline, during treatment, and as clinically indicated. Increase monitoring frequency during the first two months of treatment. Monitor patients for signs and symptoms of concurrent infection and evaluate promptly. Consider supportive measures, including the use of antimicrobials and growth factors (e.g., G-CSF) for signs of infection. Interrupt and/or reduce dose, or discontinue treatment based on the severity of the adverse reaction.

Gastrointestinal Toxicity: Patients treated with selinexor may experience gastrointestinal toxicity. Nausea/vomiting was reported in 72% of patients, with Grade 3 nausea in 9% of patients treated with selinexor. The median time to first nausea event was 3 days. Vomiting was reported in 41% of patients, with Grade 3 nausea in 4% of patients treated with selinexor. The median time to first vomiting event was 5 days. Provide prophylactic 5-HT3 antagonists and/or other anti-nausea medications prior to and during treatment with selinexor. Manage nausea/vomiting by withholding, reducing, and/or discontinuing medication. Administer IV fluids and replace electrolytes to prevent dehydration in at-risk patients. Administer additional anti-nausea medications as clinically indicated. Diarrhea was reported in 44% of patients, with Grade 3 nausea in 6% of patients treated with selinexor. The median time to first nausea event was 15 days. Manage diarrhea with dose adjustments and/or standard antidiarrheal medications; administer IV fluids to prevent dehydration in at-risk patients. Anorexia/weight loss reactions were reported in 53% of patients, with Grade 3 anorexia occurring in 5% of patients treated with selinexor. The median time to onset of anorexia was 8 days. Weight loss reactions occurred in 47% of patients, with Grade 3 weight loss occurring in 1% of patients treated with selinexor. The median time to onset of this adverse reaction was 15 days. Monitor patient weight at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Ameliorate anorexia and weight loss with dose adjustments, appetite stimulation, and nutritional support.

Hyponatremia: Selinexor can cause hyponatremia, which occurred in 39% of patients treated with selinexor and Grade 3 or 4 hyponatremia in 22%. The median time to first adverse event was 8 days. Monitor sodium levels at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. Correct sodium levels concurrent with hyperglycemia (serum glucose >150 mg/dL) and high serum paraprotein levels. Treat hyponatremia according to clinical guidelines (intravenous saline and/or salt tablets), including dietary modifications. Interrupt and/or reduce dose, or discontinue based on severity of adverse reaction.

Infection: Among patients treated with Selinexor, 52% experienced infections of varying severity. Upper respiratory tract infections of varying grades occurred in 21%, pneumonia in 13%, and sepsis in 6%. Grade ≥3 infections were reported in 25% of patients, and 4% of patients died from infection. The most common grade ≥3 infection was pneumonia in 9% of patients, followed by sepsis in 6%. The median onset time for pneumonia and sepsis was 54 days and 42 days, respectively. Most infections were not associated with neutropenia.

Neurotoxicity: 30% of patients treated with Selinexor experienced neurological adverse reactions, including dizziness, syncope, decreased level of consciousness, and mental status changes (including confusion), and 9% of patients experienced serious adverse reactions (grade 3-4). The median time to the first adverse event was 15 days. Optimize hydration status, hemoglobin levels, and supporting medications to avoid exacerbating dizziness or mental status changes.

Embryo-Fetal Toxicity: Based on data from animal studies and its mechanism of action, Selinexor may cause fetal harm when administered to a pregnant woman. Administration of Xpovio to pregnant animals during organ development has caused malformations and growth effects at exposures below the recommended clinical dose. Advise pregnant women of the potential risk to the fetus. Advise females and males of reproductive potential to use effective contraception during treatment with Selinexor and for one week after the last dose.

 

Safety and efficacy

The multicenter, single-arm SADAL trial studied 134 patients who had previously received 2 to 5 systemic treatment regimens and took selinexor 60 mg orally on days 1 and 3 of each week. The median time from the last systemic treatment to the start of selinexor treatment was 5.4 months, and the median time for patients with refractory disease was 3.6 months. Among the 134 patients, the overall response was 29%, and the complete response was 13% (18 patients). Among the 39 patients with partial or complete response, 38% had a response of at least 6 months, and 15% had a response of at least 12 months.

The Phase 2b SADAL trial was an open-label, randomized study comparing 60-mg and 100-mg levels of selinexor monotherapy twice weekly in 28-day cycles in this patient population. Initial data were presented at the 2018 ASH Annual Meeting and showed an ORR of 29.6% and a CR rate of 9.6%. The response rate was 34.0% for patients with the GCB subtype and 21.1% for patients with the non-GCB subtype. The median overall survival (OS) in the modified intention-to-treat (mITT) group was 9.1 months, with an improved median survival of 29.7 months for patients who achieved a CR or PR.

According to Shengnuoyijia, a professional medical service organization in the United States, patients will experience profound and lasting remission regardless of DLBCL subtype. Among 59 patients with GCB histology, the ORR was 33.9%, and among 63 patients with non-GCB subtypes, the ORR was 20.6%. Among the remaining 5 patients whose disease subtypes were not classified, 1 achieved CR and 2 achieved PR. Remission is usually achieved quickly, with a median DOR of 9.2 months. In the overall population, the median OS is 9 months. Among responders, the median OS has not yet been reached.