Fludarabine in Waldenstrom’s macroglobulinemia

Abstract

Waldenstrom’s macroglobulinemia is a rare chronic lymphoproliferative disorder. Treatment is usually based on nucleoside analogues, alkylators, bortezomib and monoclonal antibodies, alone or in combination. Fludarabine is a fluorinated purine analogue effective in chronic lymphoproliferative disorders. In Waldenstrom’s macroglobulinemia, fludarabine was first studied in patients with relapsed or refractory disease after alkylator therapy, yielding an overall response rate of 30%. In the late 1990s, fludarabine started to be used as a first-line treatment monotherapy yielding response rates between 36 and 94%. A recent Phase III trial showed that fludarabine monotherapy was more effective than chlorambucil in terms of progression-free survival, duration of response and overall survival. Fludarabine has also been studied in combination with rituximab and/or alkylating agents, leading to better-quality and longer lasting responses. Hematological toxicity is a major concern; however, restricting first-line use of fludarabine in patients who do not qualify for autologous stem cell transplantation, require rapid disease control or have factors of poor prognosis.

Keywords::

• fludarabine
• lymphoproliferative disorder
• nucleoside analogue
• Waldenstrom’s macroglobulinemia

Financial & competing interests disclosure

V Leblond has received honoraria from Janssen-Cilag, Mundipharma and Roche, received travel support from Roche and served on the advisory board for Janssen-Cilag, Pharmacyclics and Roche. S Choquet has served on the advisory board for Roche. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.