title: Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials.
abstract: Thalidomide and bortezomib are extensively used to treat elderly myeloma patients. In these patients, treatment-related side effects are frequent and full drug doses difficult to tolerate. We retrospectively analyzed data from 1435 elderly patients enrolled in 4 European phase III trials including thalidomide and/or bortezomib. After a median follow up of 33 months (95%CI: 10-56 months), 513 of 1435 patients (36%) died; median overall survival was 50 months (95%CI: 46-60 months). The risk of death was increased in patients aged 75 years or over (HR 1.44, 95%CI: 1.20-1.72; P<0.001), in patients with renal failure (HR 2.02, 95%CI: 1.51-2.70; P<0.001), in those who experienced grade 3-4 infections, cardiac or gastrointestinal adverse events during treatment (HR 2.53, 95%CI: 1.75-3.64; P<0.001) and in those who required drug discontinuation due to adverse events (HR 1.67, 95%CI; 1.12-2.51; P=0.01). This increased risk was restricted to the first six months after occurrence of adverse events or drug discontinuation and declined over time. More intensive approaches, such as the combination of bortezomib-thalidomide, negatively affected outcome. Bortezomib-based combinations may overcome the negative impact of renal failure. Age 75 years or over or renal failure at presentation, occurrence of infections, cardiac or gastrointestinal adverse events negatively affected survival. A detailed geriatric assessment, organ evaluation and less intense individualized approaches are suggested in elderly unfit subjects.
authors: Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliera Città della Salute e della Scienza di Torino, Torino, Italy.
authors: Sara
authors: S
authors: Bringhen
authors: Maria Victoria
authors: MV
authors: Mateos
authors: Sonja
authors: S
authors: Zweegman
authors: Alessandra
authors: A
authors: Larocca
authors: Antonietta Pia
authors: AP
authors: Falcone
authors: Albert
authors: A
authors: Oriol
authors: Davide
authors: D
authors: Rossi
authors: Maide
authors: M
authors: Cavalli
authors: Pierre
authors: P
authors: Wijermans
authors: Roberto
authors: R
authors: Ria
authors: Massimo
authors: M
authors: Offidani
authors: Juan Jose
authors: JJ
authors: Lahuerta
authors: Anna Marina
authors: AM
authors: Liberati
authors: Roberto
authors: R
authors: Mina
authors: Vincenzo
authors: V
authors: Callea
authors: Martijn
authors: M
authors: Schaafsma
authors: Chiara
authors: C
authors: Cerrato
authors: Roberto
authors: R
authors: Marasca
authors: Luca
authors: L
authors: Franceschini
authors: Andrea
authors: A
authors: Evangelista
authors: Ana-Isabel
authors: AI
authors: Teruel
authors: Bronno
authors: B
authors: van der Holt
authors: Vittorio
authors: V
authors: Montefusco
authors: Giovannino
authors: G
authors: Ciccone
authors: Mario
authors: M
authors: Boccadoro
authors: Jesus
authors: J
authors: San Miguel
authors: Pieter
authors: P
authors: Sonneveld
authors: Antonio
authors: A
authors: Palumbo
mesh_terms: D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D002423:Cause of Death; D005260:Female; D006801:Humans; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome