Lenalidomide: a review of its use in the treatment of relapsed or refractory multiple myeloma.

In several countries, including the US and in Europe, oral lenalidomide in combination with oral dexamethasone is approved for the treatment of multiple myeloma patients (aged ≥ 18 years) who have received at least one prior antimyeloma therapy. The key therapeutic mechanisms of action of lenalidomide (a thalidomide analogue) reside in its immunomodulatory, antiproliferative and anti-angiogenic properties. In patients with multiple myeloma, lenalidomide has dual effects, exerting a direct antitumour response by inhibiting proliferation and by inducing apoptosis of tumour cells. Lenalidomide also acts to enhance the immune system by inducing the activation of immune effector cells, such as T cells and natural killer cells, and inducing cytokine production. In the pivotal MM-009 and MM-010 phase III registration trials, treatment with lenalidomide plus dexamethasone was effective and had a manageable safety and tolerability profile in relapsed or refractory patients with multiple myeloma. In robust pharmacoeconomic analyses based on these trials, relative to dexamethasone, lenalidomide plus dexamethasone treatment met the assumed willingness-to-pay threshold for cost effectiveness from the UK and Scottish healthcare payer perspective in this patient population. The UK National Institute for Health and Clinical Excellence and the Scottish Medicines Consortium considered that the health economic case for lenalidomide plus dexamethasone treatment was demonstrated for patients who had received at least two prior antimyeloma therapies. In addition, in pharmacoeconomic analyses based on indirect comparisons of clinical efficacy, regulatory agencies in Norway and Sweden considered that lenalidomide plus dexamethasone treatment was cost effective relative to bortezomib in patients who have received at least one prior antimyeloma therapy. Furthermore, compared with placebo plus dexamethasone, treatment with lenalidomide plus dexamethasone significantly prolonged the median time to progression, increased overall response rates and prolonged overall survival, with significantly longer median time to progression and overall response rates observed for all subgroups of patients. Thus, combination therapy with lenalidomide plus dexamethasone provides a valuable option for the treatment of relapsed or refractory adult patients with multiple myeloma.