In patients with multiple myeloma, the survival of these patients has improved significantly since the introduction of high-dose Marfalan therapy and autologous stem cell transplantation, as well as bortezomib and immunomodulatory agents such as thalidomide and lenalidomide therapy. However, as survival increased, so did the expected survival time, thus raising the question of the increased risk of second primary malignancies in the above-mentioned patient population. Lenalidomide treatment was associated with an increased risk of second primary malignancy in the above-mentioned patient population. In this paper, Prof. Antonio et al. from Turin City Hospital, Italy, collected and analyzed the available data with the primary aim of comparing the effect of lenalidomide treatment with and without lenalidomide treatment on the risk of second primary malignancy in patients with myeloma. Secondary objectives were to assess the impact of different treatment regimens on the risk of developing second primary malignancies and to compare the risk of patients dying from second primary malignancies, progression of multiple myeloma, or treatment-related adverse events. Their findings are published in the March online issue of Lancet Oncol. The investigators began by searching abstracts of relevant studies in PubMed, the American Society of Clinical Oncology, the American Society of Hematology and the International Myeloma Symposium. The inclusion criteria for the studies were as follows; subjects were newly diagnosed patients with multiple myeloma in randomized controlled phase 3 clinical studies, the studies were conducted from January 1, 2000 to December 15, 2012, and patients in at least one of the treatment groups in these studies were treated with lenalidomide. The investigators obtained personal data on the subjects such as age, sex, time of diagnosis, treatment regimen assigned and received, duration of treatment and reasons for treatment interruption, maintenance regimen, time of first recurrence, time of diagnosis of second primary malignancy, type of second primary malignancy, by directly contacting the principal investigator of the included studies. time to death or loss to follow-up, and cause of death. The primary outcomes of the study were the cumulative risk of occurrence of all types of second primary malignancies, the cumulative risk of occurrence of second primary malignancies as solid tumors, and the cumulative risk of occurrence of second primary malignancies as hematologic tumors, and the investigators analyzed the results using a one-step meta-analysis. The investigators included nine studies that met the inclusion criteria, seven of which were able to provide personal patient information, and these studies included a total of 3,245 subjects. Three thousand two hundred and eighteen subjects were treated, of whom 2,620 were treated with lenalidomide and another 598 were not treated with lenalidomide, and data from these patients were included in the final analysis. The 5-year cumulative incidence of all types of second primary malignancies was 6.9% in patients treated with lenalidomide and 4.8% in those not treated with lenalidomide, with an HR of 1.55, a statistically significant difference between the two groups. In cases where the second primary malignancy was a solid tumor, the 5-year cumulative incidence rate was 3.8% and 3.4% in patients treated with and without lenalidomide, respectively, with an HR of 1.1, with no statistically significant difference between the two groups. In cases where the second primary malignancy was a hematologic tumor, the 5-year cumulative incidence rate was 3.1% and 1.4% in the groups of patients treated with and without lenalidomide, respectively, with an HR of 3.8, with a statistically significant difference between the two groups. Concomitant treatment with lenalidomide and oral marfalan significantly increased the risk of second primary malignancy of the hematological system in patients compared to treatment with marfalan alone, with an HR of 4.86, a statistically significant result. Concomitant treatment with lenalidomide and cyclophosphamide or co-adjuvant and dexamethasone did not significantly increase the risk of second primary hematologic malignancies compared with treatment with malfalan alone, with a HR of 0.86. Cumulative incidence of second primary malignancies as solid tumors and hematologic tumors The results of this meta-analysis indicated that for patients with newly diagnosed multiple myeloma, if the treatment regimen The results of this meta-analysis point to an increased risk of second primary hematologic malignancies in newly diagnosed multiple myeloma patients treated with lenalidomide in combination with oral marfalan. These results suggest that when developing treatment regimens for these patients, if lenalidomide is chosen, other options should be considered to replace oral marfalan therapy, such as lenalidomide in combination with cyclophosphamide or lenalidomide in combination with dexamethasone. And in patients with multiple myeloma, the risk of death comes primarily from myeloma progression or treatment-related adverse events, rather than from the second primary malignancy. Cumulative mortality of subjects dying from myeloma progression, treatment-related adverse events and second primary malignancy