Chinese instructions for Selinexor

1. Common name: Seleniso

Product name:XPOVIO, Xivio

All names: Selinexor Tablets,Selinexor, Selinexor, Probio, Selinexor Tablets

2. Indications:

1. Multiple myeloma (MM):

（1) Selinexor in combination with bortezomib and dexamethasone is indicated for the treatment of adult patients with multiple myeloma who have received at least one prior therapy.

(2) Selinisol may be indicated 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 immunomodulators, and an anti-CD38 monoclonal antibody.

2. Diffuse large B-cell lymphoma (DLBCL): Selinisol is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, unless otherwise stated, including diffuse large B-cell lymphoma caused by follicular lymphoma, after at least 2 systemic therapies.

3. Usage and dosage:

1. Recommended safety monitoring: Monitor complete blood count (CBC), including differential, standard blood chemistry, weight, nutritional status, and volume status, at baseline and during treatment as clinically indicated. Monitor more frequently during the first three months of treatment. Patients are advised to maintain adequate fluid and caloric intake throughout treatment. Consider intravenous hydration in patients at risk for dehydration. Provide prophylactic antiemetics. Administer 5-HT3 receptor antagonists and other anti-nausea agents before and during treatment with selinesol.

2. Recommended dosage:

(1) Multiple myeloma (MM): When used in combination with bortezomib and dexamethasone, the recommended dose of selinesol is 100 mg orally administered once weekly on day 1 of each week until disease progression or unacceptable toxicity occurs, concurrently with bortezomib subcutaneously on day 1 of each week 1.3 mg/m2 for 4 weeks followed by 1 week off; or dexamethasone 20 mg orally twice weekly on days 1 and 2 of each week.

The recommended dose of selinesol when combined with dexamethasone is 80 mg orally on days 1 and 3 of each week until disease progression or unacceptable toxicity occurs, and 20 mg of selinesol orally on days 1 and 3 of each week in combination with dexamethasone.

(2) Diffuse large B-cell lymphoma (DLBCL): The recommended dose of selinesol is 60 mg orally on days 1 and 3 per week until disease progression or unacceptable toxicity.

4. Adverse reactions:

In clinical studies of selinesol combination therapy for multiple myeloma, the most common adverse reactions (≥20%) were fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, weight loss, cataracts and vomiting, and grade 3-4 laboratory abnormalities (≥10%) were thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia.

In clinical studies of selinesol combination therapy for diffuse large cell lymphomaThe most common adverse reactions (≥20%) included fatigue, nausea, diarrhea, decreased appetite, weight loss, constipation, vomiting, and pyrexia, and grade 3-4 laboratory abnormalities (≥15%) included thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia.

5. Storage:

Selinesol is normally storedat or below 30°C (86°F).

6. Special groups:

1. Women: Based on the findings of animal studies and its mechanism of action, selinesol can cause fetal damage when administered to pregnant women; it is recommended that women not breastfeed during drug treatment and within 1 week after the last dose; it is recommended that women of reproductive potential use effective contraception during drug treatment and within 1 week after the last dose.

2. Men: It is recommended that men with female partners of reproductive potential use effective contraceptive measures during treatment with selinesol and within 1 week after the last dose.

7. Mechanism of action:

In nonclinical studies, selinesol reversibly inhibited the nuclear export of tumor suppressor protein (tsp), growth regulator, and oncogenic protein mRNAs by blockingexportin 1 (XPO1). Inhibition of XPO1 by selinesol leads to the accumulation of TSP in the nucleus and the reduction of several oncoproteins (such as c-myc and cyclin D1), cell cycle arrest, and apoptosis of cancer cells.

Selinesol exhibits pro-apoptotic activity in multiple myeloma cells in vitro and in multiple myeloma and diffuse macrophageAntitumor activity was demonstrated in a mouse xenograft model of B-cell lymphoma. The combination of selinesol and dexamethasone or bortezomib demonstrated synergistic cytotoxic effects in multiple myeloma in vitro and enhanced antitumor activity in mouse xenograft multiple myeloma models in vivo, including those resistant to proteasome inhibitors.