Thalidomide in combination with melphalan and prednisone is indicated as first line treatment of patients with untreated multiple myeloma, aged ≥65 years or ineligible for high dose chemotherapy.
For this indication, competent medicine agencies globally authorize below treatments:
Oral
100 - 200 mg
From 100 To 200 mg once every day
The recommended dose of thalidomide is 200 mg orally per day.
A maximum number of 12 cycles of 6 weeks (42 days) should be used.
Starting doses for thalidomide in combination with melphalan and prednisone:
| Age (years) | ANC* (/µL) | Platelet Count (/µL) | Thalidomidea,b | Melphalanc,d,e | Prednisonef | |
|---|---|---|---|---|---|---|
| ≤75 | ≥1,500 | AND | ≥100,000 | 200 mg daily | 0.25 mg/kg daily | 2 mg/kg daily |
| ≤75 | <1,500 but ≥1,000 | OR | <100,000 but ≥50,000 | 200 mg daily | 0.125 mg/kg daily | 2 mg/kg daily |
| >75 | ≥1,500 | AND | ≥100,000 | 100 mg daily | 0.20 mg/kg daily | 2 mg/kg daily |
| >75 | <1,500 but ≥1,000 | OR | <100,000 but ≥50,000 | 100 mg daily | 0.10 mg/kg daily | 2 mg/kg daily |
* ANC: Absolute Neutrophil Count
a Thalidomide dosed once daily at bedtime on Days 1 to 42 of each 42-day cycle.
b Due to the sedative effect associated with thalidomide, administration at bedtime is known to generally improve tolerability.
c Melphalan dosed once daily on Days 1 to 4 of each 42-day cycle.
d Melphalan dosing: reduce by 50% for moderate (creatinine clearance: ≥30 but <50 mL/min) or severe (CrCl: <30mL/min) renal insufficiency
e Maximum daily melphalan dose: 24 mg (subjects ≤75 years old) or 20 mg (subjects >75 years old).
f Prednisone dosed once daily on Days 1 to 4 of each 42-day cycle.
Patients should be monitored for: thromboembolic events, peripheral neuropathy, severe skin reactions, bradycardia, syncope, somnolence, neutropenia and thrombocytopenia. Dose delay, reduction or discontinuation, dependent upon the NCI CTC (National Cancer Institute Common Toxicity Criteria) grade, may be necessary.
If less than 12 hours has elapsed since missing a dose, the patient can take the dose. If more than 12 hours has elapsed since missing a dose at the normal time, the patient should not take the dose, but take the next dose at the normal time on the following day.
No specific dose adjustments are recommended for the elderly ≤75 years of age. For patients >75 years of age, the thalidomide recommended starting dose is 100 mg per day. The initial dose of melphalan is reduced for elderly >75 years of age considering baseline bone marrow reserve and renal function. The melphalan recommended starting dose is 0.1 to 0.2 mg/kg daily according to bone marrow reserve along with a further 50% dose reduction for moderate (creatinine clearance: ≥30 but <50 mL/minute) or severe (CrCl: <30 mL/minute) renal insufficiency. The maximum daily melphalan dose is 20 mg in patients >75 years of age.
Thalidomide should be taken as a single dose at bedtime, to reduce the impact of somnolence.