Patients with multiple myeloma had an increased risk of second hematologic malignancies when treated with the combination of lenalidomide (Revlimid) and melphalan, authors of a meta-analysis concluded.
Overall, lenalidomide-treated patients had a 6.9% incidence of second malignancies versus 4.8% for patients who did not receive lenalidomide (P=0.037). The difference was driven by an increased incidence of second hematologic malignancies (3.1% with lenalidomide-containing regimens versus 1.4% for other therapies, P=0.029).
Further analysis showed that lenalidomide combined with oral melphalan conferred almost a five-fold increased risk of second hematologic malignancies as compared with other lenalidomide regimens.
“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,” Antonio Palumbo, MD, of the University of Torino in Italy, and co-authors concluded in the March issue of The Lancet Oncology.
Patients with myeloma have a recognized heightened risk of second malignancies, including a twofold greater risk of hematologic malignancies, primarily myelodysplastic syndrome and acute myeloid leukemia. Multiple factors contribute to the excess risk of malignancy, including certain treatments use in myeloma.
The cytotoxic agent melphalan has one of the best characterised treatment-related malignancy risks. Recent studies suggested a heightened risk of second malignancy in myeloma patients who received lenalidomide maintenance therapy after induction with oral melphalan. The combination of lenalidomide and dexamethasone was not associated with an increased risk of second cancers.
To quantify and characterize the malignancy risk associated with lenalidomide, Palumbo and colleagues performed a meta-analysis of seven phase III trials involving a total of 3,254 patients with myeloma. The initial analysis showed a significant association between lenalidomide and any second malignancy.
Additional analyses showed no significant impact of lenalidomide on the risk of solid tumors, but the risk of second hematologic malignancies was almost four times greater in lenalidomide-treated patients (HR 3.8, 95% CI 1.15-12.62).
Examination of various lenalidomide-containing combinations identified oral melphalan as the primary culprit in the increased risk of second hematologic malignancies (HR 4.86,P<0.0001 versus melphalan alone). Hazards associated with lenalidomide and cyclophosphamide (HR 1.26, P=0.75) and dexamethasone (HR 0.86, P=0.76) reflected no increased risk of second hematologic malignancies.
Source: Med Page Today and The Lancet