Lenalidomide ( Revlimid ) has been linked to second primary malignancies in myeloma. Researchers have aimed to pool and analyse available data to compare the incidence of second primary malignancies in patients with and without Lenalidomide exposure.
Relevant studies were identified. Randomised, controlled, phase 3 trials that recruited patients with newly diagnosed multiple myeloma during the period 2000-2012, and in which at least one group received Lenalidomide were eligible for inclusion.
Primary outcomes of interest were cumulative incidence of all second primary malignancies, solid second primary malignancies, and haematological second primary malignancies, and were analysed by a one-step meta-analysis.
Researchers found nine eligible trials, of which seven had available data for 3254 patients. 3218 of these patients received treatment ( 2620 had received Lenalidomide and 598 had not ), and were included in the analyses.
Cumulative incidences of all second primary malignancies at 5 years were 6.9% in patients who received Lenalidomide and 4.8% in those who did not ( hazard ratio, HR=1.55; p=0.037 ).
Cumulative 5-year incidences of solid second primary malignancies were 3.8% in patients who received Lenalidomide and 3.4% in those that did not ( HR=1.1; p=0.72 ), and of haematological second primary malignancies were 3.1% and 1.4%, respectively ( HR=3.8; p=0.029 ).
Exposure to Lenalidomide plus oral Melphalan ( Alkeran ) significantly increased haematological second primary malignancy risk versus Melphalan alone ( HR=4.86; p less than 0.0001 ).
Exposure to Lenalidomide plus Cyclophosphamide ( Cytoxan ) ( HR=1.26; p=0.75 ) or Lenalidomide plus Dexamethasone ( HR=0.86; p=0.76 ) did not increase haematological second primary malignancy risk versus Melphalan alone.
Patients with newly diagnosed myeloma who received Lenalidomide had an increased risk of developing haematological second primary malignancies, driven mainly by treatment strategies that included a combination of Lenalidomide and oral Melphalan.
These results suggest that alternatives, such as Cyclophosphamide or alkylating-free combinations, should be considered instead of oral Melphalan in combination with Lenalidomide for myeloma. ( Xagena )
Palumbo A et al, The Lancet Oncology 2014; 15: 333-342