Ibrutinib for patients with rituximab-refractory Waldenström's macroglobulinaemia (iNNOVATE): an open-label substudy of an international, multicentre, phase 3 trial

Acquired mutations associated with ibrutinib resistance in Waldenström macroglobulinemia

“…High response rates with durable activity were also observed in a multicenter study that administered ibrutinib to heavily pre-treated, rituximab refractory WM patients. 11 Patients with CXCR4 mutations also showed delayed responses, and the 1 patient with WT MYD88 included in this study showed no response to ibrutinib. Despite the highly active nature of ibrutinib in WM, clinical progression occurs and mechanistic insights are lacking in WM.…”

Ibrutinib withdrawal symptoms in patients with Waldenström macroglobulinemia

“…The approval was based on results of a study in WM patients that showed overall response rate (ORR) of 91% and median time to response of 4 weeks [1]. Similar results were reported in another multicenter study in rituximabrefractory WM patients [2], and in a study evaluating ibrutinib as primary therapy for WM patients [3]. Temporary interruption of ibrutinib is sometimes needed to manage toxicities or perioperatively to minimize bleeding [4].…”

Cost-effectiveness analysis of ibrutinib in patients with Waldenström macroglobulinemia in Italy

“…However, not one of these options is curative and standard of care has not been established [33]. Ibrutinib, a first in-class inhibitor of BTK, displays a unique targeted mechanism of action by inhibiting downstream signalling after the interaction between the mutated MYD88 (Leu265pro) protein, present in more than 90% of patients with WM, and BTK [33][34][35].…”

“…However, not one of these options is curative and standard of care has not been established [33]. Ibrutinib, a first in-class inhibitor of BTK, displays a unique targeted mechanism of action by inhibiting downstream signalling after the interaction between the mutated MYD88 (Leu265pro) protein, present in more than 90% of patients with WM, and BTK [33][34][35]. Agents such as rituximab (alone or in combination with bortezomib or bendamustine or fludarabine), do not target disease-specific abnormalities in WM, lack efficacy in WM, and can be associated with serious AEs, particularly in older adults [36].…”

“…Moreover, the chronic utilization of non-specific developed pharmacological treatment could lead to serious AEs in WM patients with a huge economic impact on healthcare expenditure. The pivotal, single-arm, phase II trial in previously treated patients with WM who were given ibrutinib had an overall response of 91%, defining ibrutinib as the most active single agent for relapsed or refractory WM to date [16,33].…”