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The Contribution of Pets to Human and Veterinary Medicine
Published in Rebecca A. Krimins, Learning from Disease in Pets, 2020
Selinexor (Xpovio®) was approved in July 2019 for use in combination with Dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.
A drug profile on selinexor for the treatment of refractory diffuse large B-cell lymphoma
Published in Expert Review of Hematology, 2022
Selinexor has been studied in 3 phase I trials including study KCP-330-001 (NCT01607892) which involved hematologic malignancies. Selinexor has been tested at several dosages (3 to 80 mg/m2) and several schedules (1 to 3 times per week). The trial included various blood diseases: myeloma, B and T NHL, chronic lymphoid leukemia, Waldenström’s disease, acute leukemia, and chronic myeloid leukemia. Of the 79 NHLs included with a median of 4 previous lines, 43 were DLBCL [19]. In the expansion phase, patients were treated at 35 or 60 mg/m2. The dose of 35 mg/m2 (60 mg) twice a week was adopted for the phase 2 trial. Molecularly, biopsies confirmed decreased expression of Bcl-2, Bcl-6 and c-Myc, decreased Ki67 proliferation index, and nuclear localization of p53 and PTEN proteins. Of the 40 DLBCL evaluable for response, 28 were de novo DLBCL and 12 were follicular lymphoma transformations. The ORR was 25% and CR was 10% (Table 1).
Novel synthetic drugs for the treatment of non-Hodgkin lymphoma
Published in Expert Opinion on Pharmacotherapy, 2021
Farheen Manji, Robert Puckrin, Douglas A. Stewart
Selinexor is a novel selective inhibitor of nuclear export (SINE) which restores the effect of tumor suppressor genes by blocking their export from the nucleus through inhibition of the shuttling protein exportin 1 (XPO1) [104]. In a phase II study of 167 patients with relapsed/refractory DLBCL after a median 2 prior lines of systemic therapy, selinexor was administered orally at a dose of 60 mg twice weekly until disease progression or unacceptable toxicity. The ORR was 28% with 12% CR rate, mDOR 9.3mo, and mPFS 2.6mo [104]. The most common serious adverse effects of selinexor are cytopenias, anorexia, nausea, vomiting, diarrhea, fatigue, hyponatremia, infections, and neurological toxicity [105,106]. Selinexor received accelerated U.S. FDA approval for the treatment of relapsed/refractory DLBCL in June 2020. Ongoing trials are assessing the efficacy of selinexor in combination with standard R-CHOP chemoimmunotherapy for the initial treatment of DLBCL (NCT03147885), and in combination with venetoclax (NCT03955783) or salvage chemoimmunotherapy (NCT02471911, NCT04442022, NCT02741388) in the relapsed setting.
Selective inhibitors of nuclear export (SINEs) in myeloma: breakthrough or bust?
Published in Expert Opinion on Drug Safety, 2020
In summary, selinexor is an important addition to the therapeutic armamentarium of relapsed and refractory multiple myeloma. Careful attention to the management of expected side effects (particularly GI toxicities) could improve the risk/benefit ratio in these patients. Although it is currently approved in combination with dexamethasone, triplet combination therapy with additional anti-myeloma agents has a favorable outlook in unlocking the true potential for this agent for patients with advanced myeloma: overcoming refractoriness to existing class of agents and leveraging a weekly administration schedule which is likely to be better tolerated. In this context, results of the phase III BOSTON study randomizing myeloma patients with earlier disease (1–3 prior lines) to bortezomib, dexamethasone with or without selinexor are eagerly awaited (NCT03110562).