Thalidomide: reduced starting dose in patients older than age 75 years

Use a lower starting dose of thalidomide in patients with untreated multiple myeloma who are older than age 75 years.

• From: Medicines and Healthcare products Regulatory Agency
• Published: 14 December 2015
• Last updated: 14 December 2015 — See all updates

• Therapeutic area: Cancer, Haematology

Advice for healthcare professionals:

• In patients older than age 75 years, a 100 mg/day starting dose of thalidomide is now recommended to minimise the risk of adverse drug reactions
• In these patients, the starting dose of melphalan should be 0.1–0.2 mg/kg daily, according to baseline bone-marrow reserve and renal function
• Prescribers should be aware that even with a reduced starting dose of thalidomide, this age-group may be at higher risk of serious adverse reactions compared with younger patients
• Suspected adverse reactions to thalidomide should be reported to us on a Yellow Card

Thalidomide (Thalidomide Celgene) combined with melphalan and prednisone is indicated as first-line treatment of patients with untreated multiple myeloma who are age 65 years or older or who are ineligible for high-dose chemotherapy.

The new recommendation to use a 100 mg/day starting dose of thalidomide in those older than age 75 years of age is based on the results of two randomised phase III studies, one which enrolled patients age 65 years or older, and another which enrolled those age 75 years or older.^{[footnote 1]}

In patients older than age 75 years, the melphalan recommended starting dose is 0.1–0.2 mg/kg daily according to baseline bone-marrow reserve, along with a further 50% dose reduction for moderate (creatinine clearance ≥30 but < 50 mL/minute) or severe (creatinine clearance <30 mL/minute) renal insufficiency.

In the phase III study that enrolled patients age 65 years or older, the frequency of serious or fatal adverse reactions was higher in patients older than age 75 years who received thalidomide 100 mg once daily than in younger patients who received thalidomide 200 mg once daily (56.5% vs 46.5% for serious reactions and 10.3% vs 5.3% for fatal reactions, respectively). However, no clinically relevant differences were observed between these age-groups for specific serious adverse reactions, and there were no notable differences in primary causes of death between groups.

The recommended starting dose of thalidomide remains 200 mg once a day for patients age 75 years or younger.

Further information

Letter sent to healthcare professionals 10 November 2015

Article citation: Drug Safety Update volume 9 issue 5, December 2015: 1.

1. Hulin C et al. Efficacy of melphalan and prednisolone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol 2009; 27: 3664–70. ↩

Published 14 December 2015
Last updated 14 December 2015 + show all updates

1. 14 December 2015

   Thalidomide: reduced starting dose in patients older than age 75 years

2. 14 December 2015

   First published.