Main Research Findings

Selinexor, an oral exportin 1 inhibitor, has shown efficacy in treating various types of cancer, including multiple myeloma, diffuse large B-cell lymphoma, glioblastoma, and dedifferentiated liposarcoma. 5 , 10 , 11 , 12 These studies highlight its potential as a treatment option, particularly for patients who have exhausted other treatment options.

Reason for Side Effects

Selinexor's side effects are attributed to its mechanism of action, which involves inhibiting exportin 1 (XPO1), a protein responsible for exporting proteins from the cell's nucleus. This inhibition leads to an accumulation of proteins within the nucleus, potentially disrupting cellular functions and resulting in side effects.

Common Side Effects

Thrombocytopenia

A common hematologic side effect of both selinexor and belantamab mafodotin is thrombocytopenia. 2 This condition involves a decrease in the number of platelets in the blood, increasing the risk of bleeding.

Cytopenias

Selinexor can lead to cytopenias, a general term for a decrease in the number of blood cells, including white blood cells and red blood cells. 2 This can increase the risk of infections and anemia.

Constitutional Symptoms

Selinexor is associated with constitutional symptoms such as fatigue, decreased appetite, and weight loss. 2 These symptoms can significantly impact a patient's quality of life.

Gastrointestinal Effects

Selinexor can cause gastrointestinal side effects such as nausea, vomiting, and diarrhea. 4 , 2 These effects can be particularly challenging, especially for patients who have already experienced multiple rounds of treatment.

Hyponatremia

Hyponatremia, a decrease in the sodium concentration in the blood, is another potential side effect of selinexor. 2 This condition can lead to various complications if not managed appropriately.

Keratopathy

Belantamab mafodotin, another drug used for treating multiple myeloma, can cause keratopathy, a condition affecting the cornea of the eye. 2 This side effect is specific to belantamab mafodotin and not associated with selinexor.

Anemia

Belantamab mafodotin can also lead to anemia, a decrease in red blood cells, resulting in reduced oxygen-carrying capacity. 2

Measures to Counteract Side Effects

Thrombocytopenia

Thrombocytopenia can be managed through blood transfusions or the administration of thrombopoietin receptor agonists. 4

Cytopenias

Cytopenias can be addressed with medications like granulocyte colony-stimulating factors (G-CSFs) to stimulate white blood cell production. 4

Constitutional Symptoms

Constitutional symptoms like fatigue can be managed with medications such as methylphenidate, while megestrol or cannabinoids can help with decreased appetite. 4

Gastrointestinal Effects

Nausea can be mitigated with 5-HT3 antagonists and other medications like neurokinin 1 receptor antagonists, olanzapine, or cannabinoids. 4 Diarrhea can be addressed with loperamide or bismuth subsalicylate. 4

Hyponatremia

Hyponatremia is typically responsive to sodium replacement. 4

Comparison of Studies

Commonalities of Studies

Across multiple studies, selinexor has been consistently associated with side effects including thrombocytopenia, cytopenias, constitutional symptoms, gastrointestinal effects, and hyponatremia. These side effects are generally considered manageable with appropriate supportive care measures.

Differences in Studies

Studies differ in terms of the specific types and frequencies of side effects observed. This variability could be attributed to factors such as the type of cancer being treated, the patient population, and the study design. For instance, studies focusing on specific cancer types may observe different side effect profiles.

Precautions for Application to Real Life

While selinexor offers potential benefits for patients with cancer, it's crucial to be aware of its associated side effects. Open communication with healthcare providers about these risks and benefits is essential. Self-adjusting dosages or discontinuing treatment without consulting a doctor is strongly discouraged.

Limitations of Current Research

Research on selinexor is ongoing, and further investigation is needed to fully understand long-term side effects and establish its overall safety profile. Long-term follow-up studies are essential to monitor potential delayed side effects.

Future Research Directions

Future research should focus on developing strategies to mitigate or prevent selinexor-related side effects. This could include exploring new drugs or therapies to manage specific side effects, researching the impact of different dosages and treatment schedules, and conducting long-term studies to assess long-term effects and safety.

Conclusion

Selinexor holds promise as a treatment option for various cancers, particularly for patients with limited treatment options. While its effectiveness is notable, understanding its associated side effects is critical for informed decision-making. Regular monitoring and appropriate management strategies can help mitigate these side effects, ensuring patient safety and well-being. Continued research is vital to further refine our understanding of selinexor, its long-term effects, and potential strategies to enhance its safety profile.