Review of clinical trials conducted in Waldenstrom macroglobulinemia and recommendations for reporting clinical trial responses in these patients.

Many novel therapeutic agents are being tested in clinical trials for Waldenstrom macroglobulinemia (WM). However, given the paucity of large clinical trials in WM, the establishment of a standard treatment regimen that can be used for comparison of response has become challenging. We therefore performed a review of published clinical trials in WM. Systematic searches of the PubMed and Medline databases, including The Cochrane Library, were performed for the search terms: clinical trials, Waldenstrom, macroglobulinemia, and lymphoplasmacytic lymphoma. Studies of transplant in WM are beyond the scope of this review and were excluded. A total of 44 clinical trials were found in this search (38 full articles, six abstracts). Of these, 11 were performed in patients with untreated WM, 14 in patients with relapsed or refractory WM, 17 in both upfront and relapsed or refractory WM, and two studies did not provide this information. Based on this review, we recommend new response criteria and definitions of time to event analysis to be used in future clinical trials of WM. This review of the published literature would serve as a reference for comparison of response and survival analysis in current clinical trials.