1 Section of Surgery and Internal Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet2 unknown3 Section of Surgery and Internal Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
an individual patient data meta-analysis of six randomized trials
Background. Melphalan-prednisone-thalidomide (MPT) improves outcome in multiple myeloma (MM) patients, and it is now considered a standard of care for patients not eligible for transplantation. However, this treatment is a major source of morbidity. Design and Methods. An individual patient data meta-analysis (N=1680) of all the six randomized trials comparing MPT vs melphalan-prednisone (MP) was performed. The main objective was to estimate the risk of serious adverse events (AEs) and their impact on outcome. The primary endpoints were the 2-year cumulative incidence of grade 3-4 hematologic and non-hematologic AEs. Results. At least 75% of the grade 3-4 AEs occurred during the first six months of treatment in both MPT and MP groups. A higher cumulative incidence of grade 3-4 hematologic (28% vs 22%, HR 1.32, 95%CI 1.05-1.66) and non-hematologic (39% vs 17%, HR 2.78, 95%CI 2.21-3.50) AEs was documented in patients treated with MPT vs MP. Grade 3-4 non-hematologic AEs were significantly increased in patients with poor performance status. Occurrence of grade 3-4 non-hematologic AEs negatively impacted on progression-free survival (PFS) (HR 1.24, 95%CI 1.07-1.45) and overall survival (OS), (HR 1.23, 95%CI 1.03-1.47). In addition to the occurrence of AEs, PFS and OS were also negatively affected by advanced ISS stage, high creatinine levels and poor performance status. Age had a negative impact on OS as well. Conclusions. Although MPT improved outcome, it increased the incidence of toxicities, especially non-hematologic. Serious non-hematologic AEs, older age, poor performance status, and high creatinine levels have a negative impact on survival.
Acta Haematologica Polonica, 2013, Vol 98, Issue 1, p. 87-94