TORNA ALL’ELENCO

Meta-analysis of 6383 individual patient data: Second primary malignancies (SPM) in newly diagnosed multiple myeloma (MM) patients according to lenalidomide exposure in Haematologica

2013
AOU Città della Salute di Torino

Tipo pubblicazione

Conference Abstract

Autori/Collaboratori (30)Vedi tutti...

Bringhen S

Larocca A

Conticello C


et alii...

Abstract

Background. Three randomized trials recently reported an increased risk of second primary malignancies (SPMs) in newly diagnosed myeloma (MM) patients treated with lenalidomide (Len). The excess risk with lenalidomide compared with non-lenalidomide has not been described. We performed an individual patient data meta-analysis to estimate the incidence of SPM according to Len exposure. Methods. Relevant studies, from PubMed and ASCO/IMW/ASH abstracts (after 2000), that met the following criteria were included: (1) randomized trials of newly diagnosed MM patients; (2) randomization to treatment with Len in at least one arm (Lenalidomide-trials); (3) randomization to treatment to at least one new drug but not Len (no-Lenalidomide-trials); (4) available data of SPMs. The primary end point was the cumulative incidence of hematologic and solid SPMs estimated accounting for competing events. Results. 6383 patients were included in the analysis (median follow-up: 30 mos). Total cases of SPMs were 420 (6.6%), including 188 (2.9%) hematologic and 232 (3.6%) solid cancers. 3218 patients were enrolled in the lenalidomide-trials and were available for a direct comparisons between lenalidomide (Len, N=2620) vs non-lenalidomide (No-Len, N=598) treatments. The cumulative incidence rates of solid SPMs were similar in the two groups (Table) with no difference in different lenalidomide combinations. The cumulative incidence of hematologic SPMs were 1.4% at 3 years and 3.1% at 5 years in the Len group and 0.4% at 3 years and 1.4% at 5 years in the No-Len group. The observed difference was mainly attributed to the increased incidence in patients receiving Len+melphalan (1.8%) as compared with len+cyclophosphamide, (0.3%), len alone (0.3%) and melphalan only (0.4%). In multivariate age-, gender- and cluster-adjusted analysis, the association of len+melphalan increased the SPM risk of about 4-fold (HR 3.8, p<0.001) with no excess in patients receiving len+cyclophosphamide (HR 1.27,

Keywords

lenalidomide; melphalan; cyclophosphamide; new drug; human; meta analysis; multiple myeloma; patient coding; second cancer; hematology; patient; exposure; society; risk; solid; randomization; arm; Medline; myeloma; survival; death; gender; incidence; neoplasm; follow up;