Ibrutinib Plus Rituximab Data Surprising in Waldenstrom’s Macroglobulinemia

Christian Buske, MD, director, Institute of Experimental Cancer Research, attending physician, professor of medicine, Medical Department for Internal Medicine III, Hematology/Oncology, University Hospital Ulm, Ulm, Germany, discusses surprising findings from the 5-Year follow-up of a randomized phase 3 trial in patients with Waldenström’s macroglobulinemia receiving of ibrutinib (Imbruvica) plus rituximab (Rituxan) or placebo plus rituximab.

The largest surprise from the results of this trial was that efficacy was seen independent of patient’s mutational status, according to Buske. With ibrutinib monotherapy, there was a drop in efficacy relating to which mutation a patient had. When investigators look at major responses of partial response or better, there was a drop in major responses with single-agent therapy in patients with MYD88 mutations, who were double-mutated, or non-mutated. The drop in response reached 0% in patients without mutations.

There was no drop in major responses in those treated with the combination of ibrutinib and rituximab, according to Buske. This was for responses rates and progression-free survival with the study regimen, as compared with a significant shortening of progression-free survival with monotherapy in patients who were double-mutated and non-mutated. There were no major differences between genotypes in terms of efficacy, which Buske says was a surprise, as well as an important observation.