Thalidomide is licensed for use across the EU since 2008, in combination with melphalan and prednisone as first-line treatment for patients with untreated multiple myeloma who are aged 65 years or older, or those who are ineligible for high-dose chemotherapy. Thalidomide is an immunomodulatory agent, who has antineoplastic, antiangiogenic and proerythropoietic properties.
Safety results from a phase 3 study1, the results of which were supported by another study2, have highlighted a new important recommendation of a reduced initial dose of thalidomide when combined with melphalan and prednisone in patients >75 years of age with untreated multiple myeloma. The adverse reaction profile reported in patients >75 years of age treated with thalidomide 100mg daily was similar to the adverse reaction profile observed in patients ≤75 years of age treated with thalidomide 200mg once daily. However patients aged >75 years are potentially at risk for a higher frequency of serious adverse reactions. Therefore:
Advice to Healthcare Professionals
- 100mg/day starting dose is now recommended in patients >75 years of age.
- When combined with thalidomide, a reduced starting dose of melphalan should be used in patients >75 years of age.
- Patients aged >75 years are potentially at risk for a higher frequency of serious adverse reactions and should be monitored carefully.
Key message
- There is an increased risk of serious adverse reactions in patients aged over 75 years.
- Therefore a 100mg/day starting dose of thalidomide is now recommended in patients in this age group.
- A reduced starting dose of melphalan should be used in patients concomitantly taking thalidomide aged over 75 years.
- The product information (i.e. Summary of Product Characteristics (SmPC) and package leaflet (PL)) will be updated shortly to include this information. A Direct Healthcare Professional Communication (DHPC) has been circulated by the Marketing Authorisation Holder (MAH) to the relevant healthcare professionals and is available from the HPRA website (www.hpra.ie).
*Further details on Thalidomide Celgene is available on www.hpra.ie and www.ema.europa.eu
References
1. Study MM-020 – Phase 3, multicenter, randomized, open-label, 3-arm study to determine the efficacy and safety of lenalidomide plus low-dose dexamethasone when given until progressive disease or for 18 four-week cycles versus the combination of melphalan, prednisone, and thalidomide given for 12 six-week cycles in newly diagnosed MM subjects either ≥65 years or not candidates for stem cell transplant.
2. Study IFM 01/01 – Comparison of Melphalan-Prednisone (MP) to MP Plus Thalidomide in the Treatment of Newly Diagnosed Very Elderly Patients (>75 Years) With Multiple Myeloma.