Selinexor is a novel, oral, Selective Inhibitor of XPO1-mediated Nuclear Export (SINE) that was recently approved by the US FDA for the treatment of patients with penta-refractory multiple myeloma (MM). While treatment of MM has evolved remarkably over the past two decades due to the incorporation of novel and active anti-MM agents, the vast majority of patients eventually develop refractory disease and succumb to their MM. Selinexor was approved for use for patients refractory to most of these highly active agents and indicated a 25% response rate for this heavily preatreated population. These responses were associated with substantially improved survival. 1 An ongoing randomized trial, BOSTON, is evaluating the combination of selinexor, bortezomib, and dexamethasone in patients with MM who had received 1-3 prior therapies. If this trial leads to regulatory approval, the use of selinexor in everyday clinical practice will increase substantially. Therefore, a thorough insight into the safety profile of selinexor is increasingly important. This manuscript was created to better understand the side effect profile and to share management algorithms that have greatly improved patients’ experience on selinexor.
In a previous report by Kuruvilla et al., selinexor AEs were described as a ‘constellation of symptoms that form an unfamiliar toxicity paradigm’ for most hematologists. 2 This led us to consider the interconnectivity of the common AEs seen with selinexor treatment and explore the timing behind when this constellation emerges. In addition, it was apparent that some our peers in the medical community who were considering selinexor for their patients had continued questions about the management of selinexor-related AEs.
To address these questions and to shed light on side effect profile of selinexor, we analyzed safety data from 437 patients with MM treated in selinexor trials. Our goal was to provide a data-rich resource for the medical community in order to educate on what to expect, when to expect it, and how to effectively prevent and manage selinexor AEs. We show that the main side effects (nausea, vomiting, diarrhea, fatigue, decreased appetite, thrombocytopenia, and hyponatremia) are predictable, preventable, and manageable with standard support care and dose modifications. Importantly, major organ toxicities and clinically significant cumulative toxicities are not observed in the majority of patients. We conclude our report by recommending guidelines for the prevention and management of selinexor-related AEs in an effort to improve physician’s experience and patient’s quality of life. Our hope is that this resource will be an effective tool of which we can build a unified and optimal set of guidelines.
Looking forward, if there are interconnections among the common selinexor-related side effects, could the management of a few, key AEs break the constellation – or reduce the intensity or severity of multiple downstream AEs? For instance, could the aggressive, up-front control of nausea with combinations of 5HT3 antagonists and either olanzapine or NK1 antagonists lead to reduced anorexia – and in turn mitigate hyponatremia and/or weight loss? Could the control of anemia and anorexia limit the incidence of fatigue? Was Leonardo de Vinci right when he said, “fix your course on a star and you’ll navigate any storm?” As selinexor continues to be integrated into the anti-myeloma treatment landscape, we hope that further dialogue on supportive care strategies and emerging data from controlled trials will help us understand how to maximize the patient’s experience.
1 Chari A, Vogl DT, Gavriatopoulou M, Nooka AK, Yee AJ, Huff CA et al. Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma. N Engl J Med 2019; 381: 727–738.
2 Kuruvilla J, Savona M, Baz R, Mau-Sorensen PM, Gabrail N, Garzon R et al. Selective inhibition of nuclear export with selinexor in patients with non-Hodgkin lymphoma. Blood 2017; 129: 3175–3183.