Frontline treatment in multiple myeloma patients not eligible for stem-cell transplantation

Melphalan–prednisone–thalidomide (MPT) currently appears to be the treatment of choice for a large proportion of elderly patients ineligible for autologous stem-cell transplantation (ASCT). It seems certain that in the near future melphalan–prednisone–Velcade (MPV) and melphalan–prednisone–lenalidomide (MPR) will also be proved superior to melphalan–prednisone (MP), thus providing three therapeutic options (MPT, MPV and MPR) in this patient group with multiple myeloma (MM). These therapeutic options could lead to more personalized treatment approaches, based on patient comorbidities, as the three novel therapies have somewhat different toxicity profiles. MP would be appropriate for only a minority of patients with poor performance status and/or significant comorbidities, such as severe neuropathy or a contraindication to anticoagulants. Questions regarding the relative efficacy of melphalan-based regimens versus dexamethasone-based regimens (preferably with low-dose dexamethasone) will require randomized phase-III trials. More intensive approaches with new drug combinations or with the incorporation of polyethylene glycolated (PEGylated) liposomal doxorubicin will also require additional studies. Additionally, the important issue of maintenance treatment needs to be further investigated, especially in elderly patients.