Detailed explanation of the Chinese instruction manual of Seleniso

Selinexor is a new type of selective nuclear export inhibitor (SINE). By targeting and inhibiting the XPO1 (exportin 1) protein, it prevents tumor suppressor factors (TSGs), growth regulators and other key proteins from being transported from the nucleus to the cytoplasm, thereby inducing cancer cell apoptosis. It is the first XPO1 inhibitor approved by the FDA for multiple myeloma (MM) and relapsed or refractory diffuse large B-cell lymphoma (DLBCL), with the trade name XPOVIO. The drug is indicated for patients with a variety of relapsed or refractory hematological malignancies, particularly those that are resistant to conventional therapies.

1. Indications

Selinesol is mainly used to treat two types of hematological malignancies, namely multiple myeloma and diffuse largeB-cell lymphoma. Its indications specifically include:

1. Combination of bortezomib and dexamethasone: suitable for adult patients with multiple myeloma who have received at least one treatment. The program is designed to improve patient response rates to treatment and prolong progression-free survival (PFS).

2. Combined with dexamethasone: It is suitable for patients who have received at least four previous treatments (including at least two proteasome inhibitors, two immunomodulators and an antiCD38 monoclonal antibody) and whose disease has developed into refractory or relapsed multiple myeloma. This regimen is mainly used to treat patients with highly drug-resistant myeloma to delay disease progression.

3. MonotherapyDLBCL: Applicable to patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL transformed from follicular lymphoma (FL), and who have failed at least two systemic treatments. Selinisol could provide a new treatment option for DLBCL, an aggressive lymphoma in which many patients may relapse despite standard treatments.

2. Mechanism of action

Selinesol inhibitsXPO1 protein, preventing the nuclear export of various tumor suppressor proteins including p53, Rb, FOXO3A, IκB, etc., causing them to accumulate in the nucleus and continue to exert anti-cancer effects. In addition, the drug can reduce the expression levels of cancer-promoting proteins (such as c-Myc and Bcl-2), thereby inducing tumor cell apoptosis. Since XPO1 is overexpressed in a variety of cancer cells, its inhibitory effect can be widely used in different types of tumors.

3. Usage and dosage

The specific dosing regimen of selinesol varies depending on the indications:

1. Combined with bortezomib and dexamethasone: Take orally once a week, 100mg each time

2. Combined with dexamethasone: Take 80 mg orally on the 1st and 3rd day of each week to treat patients with refractory multiple myeloma.

3. MonotherapyDLBCL: 60 mg orally on the 1st and 3rd day of each week.

Patients should swallow the tablet whole after eating, and take it with enough water to reduce gastrointestinal discomfort such as nausea and vomiting. For elderly patients or patients with hepatic and renal insufficiency, dose adjustment may be necessary based on individual tolerance.

4. Adverse reactions

The most common adverse reactions of selinesol include:

Hematological toxicity: can cause thrombocytopenia (common in more than 50% of patients), neutropenia and anemia. In severe cases, medication may need to be suspended or dosage adjusted.

Gastrointestinal reactions: Nausea, vomiting, loss of appetite, diarrhea, etc. are relatively common and can be relieved by antiemetics or antidiarrhea drugs.

Fatigue and weight loss: Some patients may experience severe fatigue and weight loss, and may need dietary adjustments or nutritional supplements.

Hyponatremia: Since this drug may affect body fluid and electrolyte balance, some patients may develop hyponatremia, and serum electrolyte levels need to be measured regularly and supplemented appropriately.

Nervous system adverse reactions: Some patients may experience dizziness, cognitive dysfunction, decreased attention, etc., which require close monitoring and appropriate intervention measures.

5. Efficacy evaluation

Clinical studies have shown that selinesol has certain efficacy in patients with relapsed or refractory multiple myeloma andDLBCL. For example, in the STORM trial, more than a quarter of patients who were given the drug in combination with dexamethasone had a partial response (PR) or better to the treatment. In addition, in the SADAL study, the objective response rate (ORR) of monotherapy for DLBCL patients reached 28%, and some patients could obtain long-term remission. This suggests that selinesol offers a new treatment option for patients with certain refractory hematologic malignancies.

Reference materials:https://www.selincro.com/