Early mortality in myeloma patients treated with first-generation novel agents thalidomide, lenalidomide, bortezomib at diagnosis: A pooled analysis

Valerio De Stefano, Sergio Storti, Sara Bringhen, Massimo Offidani, Salvatore Palmieri, Francesco Pisani, Rita Rizzi, Stefano Spada, Andrea Evangelista, Nicola Di Renzo, Pellegrino Musto, Magda Marcatti, Roberto Vallone, Annalisa Bernardini, Riccardo Centurioni, Enrico Aitini, Angelo Palmas, Ombretta Annibali, Emanuele Angelucci, Paola FerrandoAnna Baraldi, Stefano Rocco, Alessandro Andriani, Agostina Siniscalchi, Vittorio Meneghini, Antonio Palumbo, Sara Grammatico, Mario Boccadoro, Alessandra Larocca

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Introduction: Early toxic death (≤60 days of diagnosis) in elderly multiple myeloma (MM) patients is attributable to active disease, age and co-morbidities. Rate of early toxic deaths is 10% with conventional chemotherapy mainly due to infection and renal failure. Novel agents have improved MM outcome at the expense of newer toxicity. Methods: We analyzed 1146 individual patient data to assess toxic deaths during induction treatment with first-generation novel agents thalidomide, lenalidomide, bortezomib. Results: During first-line therapy, 119/1146 patients (10%) died for any cause, and 47/1146 (4%) due to toxicity, including 12/1146 (1%) early deaths. The 24-month cumulative incidence was 4.1% without any difference between bortezomib (18/503 patients, 4%) and lenalidomide (29/643patients, 5%; p = 0.31). Toxic deaths occurred in 34/1039 (3%) patients <80 years and 13/107 (12%) patients ≥80 years. Causes were cardiac events (28%), infections (26%) and vascular complications (15%). In a multivariate analysis, older age and unfavorable ISS stage increased the risk of death. Conclusion: First-generation novel agents significantly reduced toxic deaths compared to conventional chemotherapy. One third of deaths during first-line therapy were due to cumulative drug-related toxicities, thus supportive approaches and prevention strategies should be optimized. The higher mortality rate for toxicity in octogenarians confirms the need for a careful frailty assessment.
Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalCRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
Volume130
DOIs
Publication statusPublished - 2018

Keywords

  • Bortezomib
  • Early mortality
  • Lenalidomide
  • Multiple myeloma
  • New drugs
  • Newly diagnosed
  • Thalidomide
  • Toxic death
  • Transplant-Ineligible

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