Practical Guidance for Managing Selinexor-Associated Adverse Events

Consensus recommendations regarding practical approaches to the management of heavily pretreated patients with multiple myeloma receiving the oral, selective nuclear transport inhibitor selinexor were published in Clinical Lymphoma Myeloma and Leukemia.¹

Based primarily on the results of the phase II STORM trial (ClinicalTrials.gov Identifier: NCT02336815), selinexor was granted accelerated approval by the US Food and Drug Administration (FDA) in 2019 for use in combination with dexamethasone for the treatment of relapsed/refractory multiple myeloma in adult patients who have been treated with at least 4 prior therapies and have disease that is refractory to treatment with at least 2 proteasome inhibitors, at least 2 immunomodulatory agents, and an anti-CD38 monoclonal antibody.²

Selinexor is a first-in-class drug indicated for a typically older, frail population of patients with multiple comorbidities. In the STORM trial, 32% of patients experienced grade 4 thrombocytopenia, with grade 3 thrombocytopenia, neutropenia, anemia, and leukopenia occurring in 27%, 19%, 42%, and 12% of patients, respectively. In addition, grade 3 fatigue was reported in 20%, hyponatremia in 20%, nausea in 10%, diarrhea in 7%, and vomiting in 3% of these patients.³

Furthermore, approximately one-quarter and one-half of patients enrolled in the STORM trial required discontinuation of study drug and selinexor dose reductions, respectively. Hence, careful monitoring and early management of adverse events is critically important to the effective delivery of selinexor in this population of patients.

These consensus recommendations emphasized 5 general strategies for managing these patients: 

• Upfront patient education regarding the high likelihood of nausea, anorexia, and fatigue. Use of patient symptom diaries where weight and other vital signs are recorded was also encouraged
• Close patient monitoring, particularly during the first cycle of selinexor, including frequent clinic visits, and hydration administered at least once weekly.
• Active involvement of nurses skilled in the management of selinexor-associated adverse events.
• Proactive administration of supportive care for mild/moderate cytopenias, anorexia, fatigue, and some gastrointestinal adverse events, as well as mild/moderate nausea.
• Prophylactic treatment for nausea and vomiting, including a 5-HT3 inhibitor, an NK1 receptor inhibitor, and olanzapine.

Additional detailed guidance, including recommendations for withholding or reducing the dose of selinexor, was provided for the management of gastrointestinal toxicity, thrombocytopenia, fatigue, and hyponatremia in patients receiving selinexor based on the grade of the adverse event. For example, monitoring platelet counts at least weekly during cycle 1, and withholding selinexor or administering platelet transfusion was recommended for those experiencing grade 4 thrombocytopenia (platelet counts less than 25,000/µL).

“We urge that patients taking [selinexor] should be monitored carefully to help overcome its unique toxicity profile, which will allow the patients the opportunity to experience the benefit of selinexor-induced prolonged remissions,” the authors of these consensus recommendations concluded.

References

1. Mikhael J, Noonan KR, Faiman B, et al. Consensus recommendations for the clinical management of patients with multiple myeloma treated with selinexor [published online March 7, 2020].  Clin Lymphoma Myeloma Leuk. doi: 10.1016/j.clml.2019.12.026

2. Selinexor [package insert]. Newton, MA: Karyopharm Therapeutics Inc.; 2019.

3. Chari A, Vogl DT, Gavriatopoulou M, et al. Oral selinexor–dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019; 381(8):727-738.