Proteasome Inhibitor-Based Regimens in the Frontline Management of Waldenström Macroglobulinemia.

Proteasome inhibitors (PIs) have long been used in myeloma therapy but also for Waldenström macroglobulinemia. Their use has been successful and has also been investigated for the frontline management of the disease. Bortezomib was effective either as a single agent or in combination with other regimens with high response rates observed in most studies, despite its adverse effects, especially neurotoxicity, which remains a major concern. Clinical trials with second-generation PIs such as carfilzomib and ixazomib have also been conducted, always in combination with immunotherapy in previously untreated patients. They have been shown to be active and neuropathy-sparing treatment options.