Lenalidomide/Melphalan Combo Associated With Increased Risk of Secondary Cancers

Results of a large meta-analysis indicated that treatment with lenalidomide for newly diagnosed multiple myeloma was associated with an increased risk for developing secondary hematologic malignancies. However, the researchers pointed out that the risk of dying from myeloma or adverse events related to its treatment are still higher than the risk of dying from a second primary malignancy.

According to background information in the article, lenalidomide has been previously linked to second primary malignancies in myeloma.

“Furthermore, three phase III trials reported an increased incidence of second primary malignancies in patients with newly diagnosed myeloma given lenalidomide maintenance after melphalan-based induction, compared with patients who did not receive lenalidomide,” wrote study author Antonio Palumbo, MD, of Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, and colleagues. “In one trial, after 3 years, invasive second primary malignancies were noted in 7% of patients who received lenalidomide and 3% of those who did not.”

To explore this link further, Palumbo and colleagues conducted a meta-analysis of all relevant published studies and abstracts presented at the meetings of the American Society of Clinical Oncology, American Society of Hematology, and the International Myeloma Workshop. They identified nine trials for inclusion, of which seven had available patient data. The results were published in Lancet Oncology.

From the included trials, 3,218 patients received treatment (2,620 with lenalidomide). At 5 years, 6.9% of patients who received lenalidomide had a second primary malignancy compared with 3.8% of patients who did not receive lenalidomide (P = .037). Although no significant difference in the cumulative 5-year incidence of solid second primary tumors was found, there was a significantly higher incidence of hematologic second primary malignancies among patients who received lenalidomide compared with those who did not (3.1% vs 1.4%; P = .029).

According to the researchers, the increased risk for hematologic second primary malignancy was driven mostly by exposure to oral melphalan. Those patients who received lenalidomide plus oral melphalan had a more than four times increased risk for hematologic second primary malignancy compared with melphalan alone (HR = 4.86; 95% CI, 2.79-8.46; P < .0001). In contrast, treatment with lenalidomide plus cyclophosphamide or lenalidomide plus dexamethasone did not increase risk.

Guy Pratt, MD, of the University of Birmingham, wrote that the risk for second primary malignancies should be of particular importance given the increased life expectancy that many new treatments have given patients with myeloma.

“The overwhelming message from this meta-analysis is that the risk of developing second primary malignancies after treatment with lenalidomide is low, and far outweighed by the risk of death from myeloma,” Pratt wrote. “Nevertheless, the combination of oral melphalan and lenalidomide might be best avoided, and alternatives used. Whether second primary malignancies will become clinically relevant as survival for patients with myeloma starts to improve beyond 7 to 10 years is uncertain.”