LuciSelin Selinexor Teblets XPOVIO

Product Name: LuciSelin

Chinese Name: Selinexor

English Name: Selinexor

[Summary]

Selinexor is an orally available nuclear export inhibitor. In non-clinical studies, Selinexor reversibly inhibits the nuclear export of tumor suppressor proteins (TSPs), growth regulators, and oncogenic protein mRNAs by blocking Exportin 1 (XPO1). Selinexor-mediated inhibition of XPO1 leads to the nuclear accumulation of TSPs, a reduction in several oncoproteins (such as c-Myc and Cyclin D1), cell cycle arrest, and apoptosis in cancer cells. Selinexor has demonstrated in vitro pro-apoptotic activity in multiple myeloma cell lines, patient tumor samples, and murine xenograft models.

[Indications]

Selinexor is indicated for the treatment of multiple myeloma in adults.

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

Selinexor may also be used for the treatment of certain types of diffuse large B-cell lymphoma in adults.

[Specification] 20 mg/tablet; 4 blisters of 8 tablets per box; Total: 32 tablets.

[Storage] Store at 20°C to 25°C (68°F to 77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F).

[Dosage and Administration]

1. Selinexor is typically taken only two days per week, in combination with dexamethasone. Please strictly follow your doctor's instructions regarding dosage and schedule; take the medication at the same time on each scheduled dosing day. Your doctor will determine the duration of your treatment with Selinexor and dexamethasone.

2. Swallow Selinexor tablets whole with a full glass of water; do not crush or chew the tablets.

3. If you vomit shortly after taking Selinexor, do not take an additional dose. Wait until your next scheduled dosing time to take the medication.

4. Usual Adult Dosage for Multiple Myeloma: 80 mg orally on Days 1 and 3 of each week, until disease progression or unacceptable toxicity occurs. 5. The recommended starting dose of dexamethasone is 20 mg, to be taken concurrently with Selinexor.

[Adverse Reactions]

Allergic reactions: Hives, difficulty breathing, swelling of the 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 medication. If any of the following side effects occur, please contact your doctor immediately:

Persistent severe nausea, vomiting, or diarrhea.

Loss of appetite, inability to eat, leading to weight loss.

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

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

Signs of infection: Fever, chills, flu-like symptoms, cough with mucus, sores in the mouth and throat, rapid heart rate, shortness of breath, or a tingling or painful blistering rash on one side of the body.

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

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

Common side effects of Selinexor may include:

Fatigue; anemia, bruising, or bleeding; fever; infection, cold or flu-like symptoms; low sodium levels; nausea, vomiting, loss of appetite; diarrhea, constipation; weight loss; shortness of breath.

[Contraindications]

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

[Precautions]

Thrombocytopenia: Selinexor can cause thrombocytopenia (low platelet count), potentially leading to fatal bleeding. Thrombocytopenia was reported as an adverse reaction in 74% of patients; severe (Grade 3 or 4) thrombocytopenia occurred in 61% of patients treated with Selinexor. The median time to the first occurrence of this adverse event was 22 days. Hemorrhage occurred in 23% of patients with thrombocytopenia, and clinically significant hemorrhage occurred in 5% of patients with thrombocytopenia.

Neutropenia: Selinexor causes neutropenia, potentially increasing the risk of infection. Neutropenia was reported as an adverse reaction in 34% of patients; severe (Grade 3–4) neutropenia occurred in 21% of patients treated with Selinexor. The median time to first onset of this adverse reaction was 25 days. Febrile neutropenia was reported in 3% of patients. Monitor neutrophil counts at baseline, during treatment, and as clinically indicated. Increase the frequency of monitoring 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 antimicrobial agents for signs of infection and growth factors (e.g., G-CSF). Interrupt and/or reduce the dose, or discontinue the drug, 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; Grade 3 nausea occurred in 9% of patients treated with Selinexor. The median time to first onset of nausea was 3 days. Vomiting was reported in 41% of patients; Grade 3 vomiting occurred in 4% of patients treated with Selinexor. The median time to first onset of vomiting was 5 days. Provide prophylactic 5-HT3 antagonists and/or other anti-nausea medications prior to and during treatment with Selinexor. Manage nausea/vomiting through dose interruption, dose reduction, and/or discontinuation of the drug. Administer intravenous fluids and electrolyte replacement to prevent dehydration in patients at risk. Use additional anti-nausea medications as clinically indicated. Diarrhea was reported in 44% of patients; Grade 3 diarrhea occurred in 6% of patients treated with Selinexor. The median time to onset of diarrhea was 15 days. Manage diarrhea through dose adjustment and/or standard antidiarrheal agents; administer intravenous fluids to patients at risk to prevent dehydration. According to reports, 53% of patients experienced anorexia/weight loss reactions; specifically, 5% of patients treated with Selinexor experienced Grade 3 anorexia. The median time to onset of anorexia was 8 days. Weight loss occurred in 47% of patients, with 1% of Selinexor-treated patients experiencing Grade 3 weight loss. 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. Manage anorexia and weight loss through dose adjustments, appetite stimulants, and nutritional support.

Hyponatremia: Selinexor can cause hyponatremia; 39% of patients treated with Selinexor experienced hyponatremia, with 22% experiencing Grade 3 or 4 hyponatremia. The median time to the 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 in the presence of concomitant hyperglycemia (serum glucose >150 mg/dL) and elevated serum paraprotein levels. Treat hyponatremia according to clinical guidelines (intravenous saline and/or salt tablets), including dietary adjustments. Interrupt and/or reduce the dose, or discontinue the drug, based on the severity of the adverse reaction.

Infections: Among patients treated with Selinexor, 52% experienced infections of varying severity. Upper respiratory tract infections of any grade occurred in 21% of patients, pneumonia in 13%, and sepsis in 6%. Grade ≥3 infections were reported in 25% of patients, and 4% of patients died due to infection. The most common Grade ≥3 infection was pneumonia (9% of patients), followed by sepsis (6% of patients). The median time to onset 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 altered mental status (including confusion); 9% of patients experienced severe adverse reactions (Grade 3–4). The median time to the first occurrence of an adverse reaction event was 15 days. Optimize hydration status, hemoglobin levels, and concomitant medications to avoid exacerbating dizziness or changes in mental status.

Embryo-Fetal Toxicity: Based on data from animal studies and its mechanism of action, Selinexor may cause fetal harm when administered to pregnant women. Administration of Xpovio to pregnant animals during organogenesis resulted in malformations, and growth was impaired at exposures below the recommended clinical dose. Pregnant women should be advised of the potential risk to the fetus. Women and men of reproductive potential are advised 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 evaluated 134 patients who had previously received 2 to 5 lines of systemic therapy regimens; these patients received oral Selinexor 60 mg on Days 1 and 3 of each week. The median time from the last systemic therapy to the initiation of Selinexor treatment was 5.4 months, and 3.6 months for patients with refractory disease. Among the 134 patients, the overall response rate was 29%, with a complete response rate of 13% (18 patients). Among the 39 patients who achieved a partial or complete response, 38% maintained their response for at least 6 months, and 15% maintained their response for at least 12 months.

The Phase 2b SADAL trial was an open-label, randomized study in which investigators compared the efficacy of Selinexor monotherapy administered twice weekly at doses of 60 mg versus 100 mg (in 28-day cycles) in this patient population. Initial data, presented at the 2018 ASH Annual Meeting, indicated an ORR of 29.6% and a CR rate of 9.6%. The response rate was 34.0% in patients with the GCB subtype and 21.1% in patients with the non-GCB subtype. The median overall survival (OS) in the modified intent-to-treat (mITT) population was 9.1 months; for patients who achieved a CR or PR, the median survival was improved to 29.7 months. According to Sino-One, a specialized U.S. medical services provider, patients achieved profound and durable remissions regardless of their DLBCL subtype. Among the 59 patients with GCB histology, the ORR was 33.9%; among the 63 patients with the non-GCB subtype, the ORR was 20.6%. Of the remaining 5 patients whose disease subtypes were unclassified, one achieved a CR and two achieved a PR. Remissions were typically achieved rapidly, with a median DOR of 9.2 months. In the overall patient population, the median OS was 9 months. Among those who achieved remission, the median OS has not yet been reached.