REVLIMID

What it is

REVLIMID is lenalidomide supplied as capsules. The medicine is available in seven strengths: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg, and 25 mg. REVLIMID (lenalidomide) is structurally related to thalidomide. REVLIMID capsules should be administered orally at about the same time each day, swallowed whole (not opened, broken or chewed), preferably with water and either one hour before or two hours after food.

Approved indications

— Treatment of multiple myeloma. — Treatment of patients with transfusion-dependent anaemia due to low- or intermediate-1 risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality with or without additional cytogenetic abnormalities. — Treatment of patients with relapsed and/or refractory mantle cell lymphoma.

Dosing overview

Treatment must be initiated and monitored under the supervision of a registered Specialist Physician experienced in the management of haematological and oncological malignancies. Dosing varies substantially by indication and patient factors. For newly diagnosed multiple myeloma in patients ineligible for transplant receiving REVLIMID in combination with bortezomib and dexamethasone, the recommended starting dose is 25 mg once daily on Days 1–14 of 21-day cycles for up to eight cycles, followed by continuation with dexamethasone at 25 mg once daily on Days 1–21 of repeated 28-day cycles. For newly diagnosed transplant-ineligible patients aged 75 years or younger, the starting dose is 25 mg once daily on Days 1–21 of repeated 28-day cycles with dexamethasone 40 mg once daily on Days 1, 8, 15 and 22; for those over 75 years, dexamethasone is reduced to 20 mg on the same days. For newly diagnosed patients post-transplant receiving maintenance monotherapy, the starting dose is 10 mg once daily continuously on Days 1–28 of repeated 28-day cycles, with potential increase to 15 mg daily after 3 months if tolerated. For myelodysplastic syndromes, the starting dose is 10 mg once daily on Days 1–21 of repeated 28-day cycles. For previously treated mantle cell lymphoma, the starting dose is 25 mg once daily on Days 1–21 of repeated 28-day cycles. Lenalidomide is substantially excreted by the kidney, and dose adjustments are recommended for patients with renal impairment based on creatinine clearance.

Key safety warnings

REVLIMID must not be used during pregnancy as it may cause birth defects or death to an unborn baby; women should avoid pregnancy whilst taking REVLIMID, during dose interruptions, and for 4 weeks after stopping the medication. REVLIMID is only available through the i-access Pregnancy Prevention Program, under which only registered physicians and pharmacists can prescribe and dispense the product, and it must only be dispensed to registered patients who meet all program conditions. Neutropenia and thrombocytopenia are major dose-limiting toxicities; patients with neutropenia should be monitored for signs of infection and advised to promptly report febrile episodes, and patients and physicians should be observant for signs and symptoms of bleeding including petechiae and epistaxis, especially with concomitant medications that may increase bleeding risk. In patients with multiple myeloma, the combination of REVLIMID with dexamethasone is associated with an increased risk of venous thromboembolism (predominantly deep vein thrombosis and pulmonary embolism) and arterial thromboembolism (predominantly myocardial infarction and cerebrovascular events); the risk of both is lower with REVLIMID monotherapy. Patients and physicians are advised to be observant for signs and symptoms of thromboembolism; patients should seek medical care if they develop shortness of breath, chest pain, or arm or leg swelling, and prophylactic antithrombotic medicines such as low molecular weight heparins or warfarin should be considered, especially in patients with additional thrombotic risk factors. Rare cases of angioedema, anaphylaxis and serious dermatological reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported; REVLIMID must be discontinued for these reactions and should not be resumed. Hepatic failure, including fatal cases, has been reported in patients treated with REVLIMID in combination with dexamethasone; abnormal liver function tests have been commonly reported and were generally asymptomatic and reversible upon dosing interruption, and monitoring of liver function is recommended particularly when there is a history of or concurrent viral liver infection.

Contraindications

REVLIMID is contraindicated in women who are pregnant. REVLIMID is contraindicated in women of childbearing potential unless all conditions of the i-access Program are met. REVLIMID is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients.

PBS listing

REVLIMID capsules 5 mg, 10 mg, 15 mg and 25 mg are listed on the PBS with authority required restriction; ex-manufacturer prices are A$248.50 (5 mg), A$651.10 (10 mg), A$784.18 (15 mg) and A$512.99 (25 mg) respectively. The 20 mg capsule was recommended for listing in November 2023 under the same circumstances as the 25 mg capsule, cost-minimised on a per mg basis.

Regulatory history

REVLIMID was first registered on the ARTG on 20 December 2007 in strengths of 5 mg, 10 mg, 15 mg and 25 mg. Additional strengths of 2.5 mg, 7.5 mg and 20 mg were registered on 11 November 2015. In November 2014, the PBAC recommended extending the listing of lenalidomide for multiple myeloma to include patients who have received at least one prior therapy. In March 2016, the PBAC recommended listing of lenalidomide in combination with dexamethasone as first line therapy for newly diagnosed multiple myeloma patients ineligible for stem cell transplant under the Highly Specialised Drugs Program. In March 2016, the TGA approved an application to extend the registration of REVLIMID for the treatment of patients with relapsed and/or refractory mantle cell lymphoma. In July 2019, the PBAC recommended listing for maintenance treatment of patients with newly diagnosed multiple myeloma who have undergone autologous stem cell transplant under the Highly Specialised Drugs Program with authority required restriction. In August 2019, the PBAC recommended listing in combination with bortezomib and dexamethasone for newly diagnosed multiple myeloma patients ineligible for primary stem cell transplant under the Highly Specialised Drugs Program.