On 22 June 2020, the US Food and Drug Administration (FDA) granted accelerated approval to selinexor (XPOVIO, Karyopharm Therapeutics) for adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least 2 lines of systemic therapy.<\/p>\n
XPOVIO is a nuclear export inhibitor, available in tablets for oral use.<\/p>\n
Approval was based on SADAL (KCP-330-009; NCT02227251), a multicentre, single-arm, open-label trial in patients with DLBCL after 2 to 5 systemic regimens. Patients received selinexor 60 mg orally on days 1 and 3 of each week. <\/p>\n
Efficacy was based on overall response rate (ORR) and response duration, as assessed by an independent review committee using Lugano 2014 criteria. In 134 patients, the ORR was 29% (95% confidence interval 22, 38), with complete response in 13%. Of the 39 patients who achieved a partial or complete response, 38% had response durations of at least 6 months and 15% had response durations of at least 12 months.<\/p>\n
The most common adverse reactions (incidence \u226520%) in patients with DLBCL, excluding laboratory abnormalities, were fatigue, nausea, diarrhoea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3-4 laboratory abnormalities in \u226515% were thrombocytopenia, lymphopenia, neutropenia, anaemia, and hyponatremia. Serious adverse reactions occurred in 46% of patients, most often from infection. Thrombocytopenia was the leading cause of dose modifications. Gastrointestinal toxicity developed in 80% of patients and any grade hyponatremia developed in 61%. Central neurological adverse reactions occurred in 25% of patients, including dizziness and mental status changes.<\/p>\n
The prescribing information provides warnings and precautions for thrombocytopenia, neutropenia, gastrointestinal toxicity, hyponatremia, serious infection, neurological toxicity, and embryo-foetal toxicity.<\/p>\n
The recommended selinexor dosage for patients with DLBCL is 60 mg taken orally on days 1 and 3 of each week with antiemetic prophylaxis.<\/p>\n
Full prescribing information for XPOVIO is available here<\/a>.<\/p>\n This indication was approved under accelerated approval based on response rate. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.<\/p>\n This application was granted priority review and Fast Track designation.<\/p>\n Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA\u2019s MedWatch Reporting System.<\/p>\n For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA\u2019s Oncology Center of Excellence<\/a> Project Facilitate<\/a>.<\/p>\n