Lenalidomide as first line of treatment
Lenalidomide is a derivative of thalidomide and exerts multiple actions including anti-myeloma, anti-inflammatory and anti-angiogenic (inhibiting new blood vessel formation) activities. For transplant-ineligible patients at first line, lenalidomide is accepted for restricted use in combination with dexamethasone for those patients who are intolerant or contraindicated to thalidomide. More recently in 2023, it was also approved in combination with daratumumab (Darzalex ®) and dexamethasone. Lenalidomide is generally preferred to thalidomide for non-transplant eligible patients who are on a non-PI containing regimen.
Efficacy
Evidence for the safety and efficacy of lenalidomide comes from a number of Phase 3 trials, including the FIRST trial (MM-020) which showed that progression free survival (PFS) was significantly longer in patients receiving continuous lenalidomide and dexamethasone (25.5 months) compared to those receiving MPT (21.2 months). Median overall survival (OS) was 59 months versus 49 months respectively and patients in the lenalidomide arm had a 25% reduction in the risk of death compared to patients in the MPT arm.
Administration
Lenalidomide is taken as a single oral dose. Individual treatment plans vary and the dose can be altered if toxicity is significant, for example in cases of renal impairment. Often the starting dose is lower in older, frailer patients. Lenalidomide is normally taken for 21 days followed by a 7-day rest period. This forms one 28-day (4 week) cycle.
Common side effects of lenalidomide containing regimens
| Treatment | Potential side effects |
|---|---|
| Lenalidomide | Gastrointestinal symptoms including diarrhoea, fatigue, increased thrombotic risk, peripheral neuropathy, low blood counts (neutrophils and platelets), skin rashes, birth defects |
| Dexamethasone | Stomach irritation, increased appetite, fluid retention, swelling in feet and hands, changes in blood sugar levels, infections, mood swings, insomnia, muscular problems, eye complications |
Recent research has identified that lenalidomide-induced diarrhoea may be caused by bile acid malabsorption. Where appropriate, patients should be tested for bile acid malabsorption and started on bile acid sequestrant treatment e.g. colosevelam and/or reduce the amount of fat in the diet. This has been shown to improve symptoms and quality of life and allowed patients to continue with lenalidomide long term.
Further information on lenalidomide is described in the “Treatment at second relapse” section.