Use of Thalidomide, Lenalidomide, Carfilzomib, Bortezomib and Vorinostat in the Initial Treatment of Newly Diagnosed Multiple Myeloma Patients

Days 1 \& 8 - cyclophosphamide 500 mg PO Days 1-21 - lenalidomide 25 mg daily PO Days 1-4 \& 12-15 - dexamethasone 40 mg daily PO This cycle is repeated every 28 days

Days 1,8,15 (i.e. weekly) - cyclophosphamide 500 mg PO Continuously - thalidomide 50 mg hard capsules. Initially 100 mg daily PO for 3 weeks, increasing to 200 mg daily PO Days 1-4 and 12-15 - dexamethasone 40 mg daily PO The cycle is repeated every 21 days

Days 1 \& 8 - cyclophosphamide 500 mg PO Days 1 \& 2, 8 \& 9, 15 \& 16 - carfilzomib 20\*/36 mg/m2\*\* IV (\*carfilzomib 20 mg/m2 is only administered on days 1 and 2 of cycle 1; \*\*carfilzomib will be dose capped at a body surface area of 2.2 m2) Days 1-21 - lenalidomide 25 mg daily PO Days 1-4, 8, 9 \& 15, 16 - dexamethasone 40 mg daily PO This cycle is repeated every 28 days

Days 1 \& 8 - cyclophosphamide 500 mg PO Days 1-21 - lenalidomide 25 mg daily PO Days 1-4 \& 15-18 - dexamethasone 20 mg daily PO This cycle is repeated every 28 days

Days 1, 8, 15, 22 (weekly) - cyclophosphamide 500 mg PO Continuously - thalidomide 50 mg hard capsules; initially 50 mg daily PO for 4 weeks, increasing every 4 weeks by 50 mg increments to 200 mg daily PO Days 1-4 \& 15-18 - dexamethasone 20 mg daily PO This cycle is repeated every 28 days

Days 1, 4, 8 \& 11 - bortezomib 1.3 mg/m2 SC or IV Days 1, 8, 15 - cyclophosphamide 500 mg PO Days 1-2, 4-5, 8-9 \& 11-12 - dexamethasone 20 mg daily PO This cycle is repeated every 21 days

Days 1-21 - lenalidomide 10 mg daily PO This cycle is repeated every 28 days

Days 1-21 - lenalidomide 10 mg daily PO Days 1-7 \& 15-21 - vorinostat 300mg PO This cycle is repeated every 28 days

High dose melphalan therapy and autologous stem cell transplant to be given as per local practice