Article date: November 2011
Lenalidomide (Revlimid▼) is authorised in combination with dexamethasone for treatment of multiple myeloma in patients who have received at least one previous treatment. Lenalidomide is an immunomodulatory agent similar to thalidomide, which has antineoplastic, antiangiogenic, and antierythropoietic properties.
In May 2011 we published an article in Drug Safety Update on the preliminary investigation of a signal from clinical trials in which lenalidomide was given as maintenance treatment for patients with newly diagnosed multiple myeloma. Importantly, this treatment population falls outside the currently authorised indication. The data showed an apparent excess of second primary malignancy in patients treated with lenalidomide (including: haematological malignancies such as acute myeloid leukaemia, Hodgkin’s disease, and B-cell lymphocytic leukaemias; myelodysplastic syndrome; solid tumours; and melanomas).
Following this, a Europe-wide review relating to the risk of second primary malignancy in patients treated for the authorised indication of relapsed or refractory multiple myeloma has been conducted, in order to determine the balance of risks and benefits of lenalidomide, taking into consideration the availability of alternative treatment options for these patients (which were not available when the licence was granted for lenalidomide).
Risk of second primary malignancy in patients with relapsed or refractory myeloma
To date, there have been eight case reports (from the pivotal clinical trials of 353 patients assigned lenalidomide and 350 controls that supported the license application for lenalidomide) of invasive second primary malignancy (excluding non-melanoma skin cancer), one of whom had died as a result of the reported second malignancy and four of whom had died from other causes; three remained alive. The incidence of invasive second primary malignancy (excluding non-melanoma skin cancer) for lenalidomide-exposed patients was 1.71 versus 0.91 per 100 patient-years for the control group).
The incidence of second primary malignancy (including non-melanoma skin cancer) in lenalidomide-treated patients was 3.98 per 100 patient-years compared with 1.38 per 100 patient-years for controls. Non-invasive second primary malignancies comprise basal-cell or squamous-cell skin cancers. Most invasive second primary malignancies were solid tumours (incidence rate 1.28 per 100 patient-years).
The available evidence suggests that there may be a small increased risk of development of second primary malignancy. Overall in the trials this was compensated by greater overall survival and progression-free survival in patients treated with lenalidomide for relapsed or refractory myeloma. The balance of benefits and risks for lenalidomide remains favourable in its licensed indication.
Risk of second primary malignancy in patients newly diagnosed myeloma
In clinical trials of newly diagnosed multiple myeloma (unauthorised indication), a four-fold increased incidence of second primary malignancy has been observed in patients receiving lenalidomide (7.0 %) compared with controls (1.8%). The median follow-up for participants with newly diagnosed myeloma in clinical trials ranges from 27.2 months to 36.5 months.
The available data do not allow identification of potential risk factors for the development of second primary malignancy, therefore, the possibility of second malignancy should be considered in all patients treated with lenalidomide.
Advice for healthcare professionals:
- use of lenalidomide in unlicensed indications is not recommended unless it takes place as part of a clinical trial
- patients should be carefully evaluated before and during treatment with lenalidomide using routine cancer screening for occurrence of second primary malignancy and treatment should be instituted as indicated
- healthcare professionals should report all suspected adverse reactions, including second primary malignancy promptly to us via the Yellow Card Scheme
Letter sent to healthcare professionals sent October 2011
European Public Assessment Reports for lenalidomide
BNF section 8.2.4 Other immunomodulating drugs
Article citation: Drug Safety Update Nov 2011, vol 5 issue 4: A1.