XPOVIO

What it is

XPOVIO contains selinexor 20 mg per film-coated tablet. Selinexor is a reversible covalent selective inhibitor of nuclear export (SINE) compound that specifically blocks exportin 1 (XPO1). XPO1 is a major nuclear export protein that transports cargo proteins and several classes of mRNA from the nucleus to the cytoplasm. XPO1 cargoes include many tumour suppressor proteins, growth regulator proteins and mRNAs of growth promoting proteins. XPO1 inhibition by selinexor leads to marked accumulation of tumour suppressor proteins and growth regulator proteins in the nucleus, and reduced expression of several oncoproteins and translation/chaperon proteins, resulting in cell cycle arrest and apoptosis of cancer cells. This medicinal product is subject to additional monitoring in Australia. This will allow quick identification of new safety information.

Approved indications —

In combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. — In combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least three prior therapies and whose disease is refractory to at least one proteasome inhibitor, at least one immunomodulatory medicinal product (IMiD), and an anti-CD38 monoclonal antibody (mAb).

Dosing overview

The tablet should be swallowed whole with water. It should not be crushed, chewed, broken or divided in order to prevent risk of skin irritation from the active substance. It can be taken with or without food. Treatment must be initiated and monitored under supervision of physicians experienced in the management of multiple myeloma.

Key safety warnings

XPOVIO can cause life-threatening thrombocytopenia or may increase thrombocytopenia induced by concomitant therapy, leading to potentially fatal haemorrhage. Patients should have their complete blood counts assessed at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. XPOVIO can cause life-threatening neutropenia, potentially increasing the risk of infection. XPOVIO can cause serious and fatal infections. Most of these infections were not associated with Grade 3 or higher neutropenia. Atypical infections reported after XPOVIO include, but are not limited to, fungal pneumonia and herpesvirus infection. XPOVIO can cause severe gastrointestinal toxicities. Grade 3 or higher nausea/vomiting events have occurred and there have been events that resulted in permanent discontinuation. Provide prophylactic 5-HT3 antagonists and other anti-nausea agents, prior to and during treatment with XPOVIO. XPOVIO can cause fatigue, weight loss, and anorexia. Grade 3 fatigue, weight loss and anorexia events have occurred and there have been events that resulted in permanent discontinuation. XPOVIO can cause severe or life-threatening hyponatraemia. Monitor sodium level at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first two months of treatment. XPOVIO can cause life-threatening neurological toxicities including confusional state and dizziness. New onset or exacerbation of cataract has occurred during XPOVIO therapy.

Contraindications

Hypersensitivity to the active substance or to any of the excipients.

PBS listing

XPOVIO 20 mg tablets are listed on the PBS with six items. The restriction type is authority required, and the ex-manufacturer price is A$11,700.00.

Regulatory history

XPOVIO selinexor 20 mg tablets were first registered on the ARTG on 8 March 2022. The AusPAR approval date was 3 March 2022, for use in combination with bortezomib and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least one prior therapy, and in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least three prior therapies and are refractory to specific prior treatments. The PBAC initially did not recommend XPOVIO in July 2021 for triple class refractory/penta-refractory multiple myeloma, relapsed and/or refractory diffuse large B-cell lymphoma, and relapsed and/or refractory multiple myeloma. In March 2022, the PBAC recommended XPOVIO for triple class refractory/penta-refractory multiple myeloma in combination with dexamethasone. In March 2022, the PBAC did not recommend XPOVIO for relapsed and/or refractory multiple myeloma in combination with bortezomib and dexamethasone. In November 2022, the PBAC recommended XPOVIO for multiple myeloma (relapsed and/or refractory, in combination with bortezomib and dexamethasone, in patients who have received at least one prior therapy).