Risk for infections with selinexor in patients with relapsed/refractory multiple myeloma: a systematic review of clinical trials

The outcomes of patients with relapsed/refractory multiple myeloma (RRMM) remain poor despite recent therapeutic advances. One of the newest treatments for RRMM is selinexor (Xpovio; KPT-330), a first-in-class selective inhibitor of nuclear export (SINE) that blocks the nuclear export protein exportin 1 (XPO1) [ 1 Chen C. Siegel D. Gutierrez M. et al. Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia. Blood. 2018; 131: 855-863 Crossref PubMed Scopus (81) Google Scholar , 2 Vogl D.T. Dingli D. Cornell R.F. et al. Selective inhibition of nuclear export with oral selinexor for treatment of relapsed or refractory multiple myeloma. J Clin Oncol. 2018; 36: 859-866 Crossref PubMed Scopus (95) Google Scholar , 3 Chari A. Vogl D.T. Gavriatopoulou M. et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019; 381: 727-738 Crossref PubMed Scopus (230) Google Scholar , 4 Bahlis N.J. Sutherland H. White D. et al. Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. Blood. 2018; 132: 2546-2554 Crossref PubMed Scopus (80) Google Scholar , 5 Gasparetto C. Lentzsch S. Schiller G. et al. Selinexor, daratumumab, and dexamethasone in patients with relapsed or refractory multiple myeloma. eJHaem. June 2021; 193 (e43-e47): 1019-1287https://onlinelibrary.wiley.com/doi/10.1002/jha2.122 Google Scholar , 6 Jakubowiak A.J. Jasielec J.K. Rosenbaum C.A. et al. Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma. Br J Haematol. 2019; 186: 549-560 Crossref PubMed Scopus (39) Google Scholar , 7 Grosicki S. Simonova M. Spicka I. et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020; 396: 1563-1573 Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar ]. In 2019, the US Food and Drug Administration (FDA) granted accelerated approval to selinexor, in combination with dexamethasone, for patients with RRMM who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors (PIs), at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody [ [3] Chari A. Vogl D.T. Gavriatopoulou M. et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019; 381: 727-738 Crossref PubMed Scopus (230) Google Scholar ]. In late 2020, the FDA approved selinexor in combination with bortezomib and dexamethasone (SVd) for the treatment of patients with MM who have received at least one prior therapy [ [7] Grosicki S. Simonova M. Spicka I. et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020; 396: 1563-1573 Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar ]. While haematological adverse events (AEs) are the most common grade III–IV AEs associated with selinexor [ 1 Chen C. Siegel D. Gutierrez M. et al. Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia. Blood. 2018; 131: 855-863 Crossref PubMed Scopus (81) Google Scholar , 2 Vogl D.T. Dingli D. Cornell R.F. et al. Selective inhibition of nuclear export with oral selinexor for treatment of relapsed or refractory multiple myeloma. J Clin Oncol. 2018; 36: 859-866 Crossref PubMed Scopus (95) Google Scholar , 3 Chari A. Vogl D.T. Gavriatopoulou M. et al. Oral selinexor-dexamethasone for triple-class refractory multiple myeloma. N Engl J Med. 2019; 381: 727-738 Crossref PubMed Scopus (230) Google Scholar , 4 Bahlis N.J. Sutherland H. White D. et al. Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. Blood. 2018; 132: 2546-2554 Crossref PubMed Scopus (80) Google Scholar , 5 Gasparetto C. Lentzsch S. Schiller G. et al. Selinexor, daratumumab, and dexamethasone in patients with relapsed or refractory multiple myeloma. eJHaem. June 2021; 193 (e43-e47): 1019-1287https://onlinelibrary.wiley.com/doi/10.1002/jha2.122 Google Scholar , 6 Jakubowiak A.J. Jasielec J.K. Rosenbaum C.A. et al. Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma. Br J Haematol. 2019; 186: 549-560 Crossref PubMed Scopus (39) Google Scholar , 7 Grosicki S. Simonova M. Spicka I. et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet. 2020; 396: 1563-1573 Abstract Full Text Full Text PDF PubMed Scopus (73) Google Scholar ], infections are a major cause of poor outcomes in these patients. Hence, an antineoplastic agent with potential adjunctive anti-viral properties holds potential for improved outcomes. Selinexor has also been shown to reduce the risk of viral infections by blocking virion export from the nucleus, an effect also mediated through SINE inhibition [ [8] Uddin M.H. Zonder J.A. Azmi A.S. Exportin 1 inhibition as antiviral therapy. Drug Discov Today. 2020; 25: 1775-1781 Crossref Scopus (22) Google Scholar ]. While infections are frequently reported with all anti-myeloma agents, the incidence and risk of infections with selinexor are unknown. Therefore, we conducted a systematic review of clinical trials to determine the incidence of severe infections associated with selinexor in patients with RRMM.