First-Line Treatment of Multiple Myeloma in Elderly Patients: the GIMEMA (Gruppo Italiano Malattie EMatologiche dellAdulto) Multiple Myeloma Working Party Perspective

Pellegrino      Musto; Fiorella      D'Auria; Giuseppe      Pietrantuono; Luca      Baldini; Sara      Bringhen; Tommaso      Caravita; Francesco      Di Raimondo; Fortunato      Morabito; Massimo      Offidani; Maria   Teresa   Petrucci; Patrizia      Tosi; Francesca      Gay; Michele      Cavo; Mario      Boccadoro; Antonio      Palumbo

Abstract

Multiple myeloma (MM) is a neoplastic disorder affecting elderly people. The treatment for all patients with MM was, for about 40 years, based on the combination of melphalan plus prednisone, with a very low rate of complete remissions and a survival that remained unacceptably low (about 36 months). Diverse factors, including comorbidity, performance status, decreased physiologic reserve, and potential undertreatment, contribute to these poor outcomes. Recently, however, the reduced treatment-related morbidity and mortality associated with autologous stem-cell transplantation and the availability of effective new drugs with acceptable toxicity, such as thalidomide, lenalidomide and bortezomib, have greatly modified the traditional treatment paradigms in older patients with MM, challenging, in some cases, the definition of elderly and rapidly transforming the traditional palliative treatments to a new global therapeutic strategy, with the final objective of significantly improving the quality and the duration of life for elderly people with this disease. In this review, we report updated data for the front-line treatment of MM in the elderly population, examining the role of new drugs combined with melphalan or their incorporation within more complex combinations, including other so-called conventional drugs such as (pegylated)-doxorubicin, cyclophosphamide, and dexamethasone. We also assess the role of autologous and allogeneic stem-cell transplantation with adjusted conditioning regimens in selected elderly patients.

Keywords: Myeloma, elderly, thalidomide, lenalidomide, bortezomib, doxorubicin, cyclophosphamide, dexamethasone, bendamustine, autologous transplantation