Evaluating ibrutinib in the treatment of symptomatic Waldenstrom’s macroglobulinemia

Figures & data

Table 1 Overview of clinical studies evaluating ibrutinib-based regimens among patients with WM

Study	Phase	Number of patients	Design	ORR	Major RR	PFS	OS	Toxicities
Advani (2013)	I	4	Prospective Relapsed/refractory patients received PO ibrutinib	3 of 4 patients achieved a response	Not reported	Not reported	Not reported	Grades 3–4: neutropenia 12.5%, thrombocytopenia 7.2%, anemia 7.1%
Treon (2015)	II	63	Prospective Previously treated patients received PO ibrutinib	90.5%	73%	2-year PFS rate: 69.1%	2-year OS rate: 95.2%	Grades 2–4: neutropenia 22%, thrombocytopenia 14%, anemia 6%, AF 5%, pneumonia 8%, hemorrhage 2%
Dimopoulos (2016)	III	31	Open-label Rituximab-refractory patients received per os (PO) ibrutinib	90%	71%	18-month PFS rate: 86%	18-month OS rate: 97%	Grade 3 or worse: neutropenia 13%, thrombocytopenia 6%, anemia 6%, hypertension 10%, infections 16%
Dimopoulos (2018)	III	150	Randomized-controlled trial 1:1 randomized to receive rituximab+ibrutinib OR rituximab+placebo	Significantly higher in the ibrutinib arm compared to the placebo arm (92% vs 47%)	Significantly higher in the ibrutinib arm compared to the placebo arm (72% vs 32%)	30-month PFS rate: 82% (ibrutinib–rituximab) vs 28% (placebo–rituximab)	30-month OS rate: 94% (ibrutinib–rituximab) vs 92% (placebo–rituximab)	Grade 3 or 4 in the ibrutinib vs placebo arm: hypertension 13% vs 4%, AF 12% vs 1%, anemia 11% vs 17%, neutropenia9 % vs 3%, pneumonia 9% vs 3%, IRR 1% vs 16%
Treon (2018)	2	30	Prospective Untreated patients received PO ibrutinib The effect of CXCR4 status on outcome was investigated 47% carried CXCR4 mutation	100% for all patients	83% for all patients/94% in WT CXCR4/71% in CXCR4 mutated	18-month PFS rate: 92%	18-month OS rate: 100%	Grades 2–3 (No grade 4 toxicities): hypertension 13%, AF 10%, neutropenia 7%, upper respiratory tract infection 7%, urinary tract infection 7%

Abbreviations: ORR, overall response rate; Major RR, major response rate; PFS, progression-free survival; OS, overall survival; AF, atrial fibrillation; WM, Waldenstrom’s macroglobulinemia.

Table 2 Major ongoing trials of ibrutinib-based regimens in WM

NCT number	Phase	Design	Status
NCT02604511	II	Single-arm open-label study of ibrutinib in treatment-naïve patients with WM and its impact on tumor genomic evolution	Active, not recruiting
NCT03225716	I/II	Open-label study of ibrutinib+ulocuplumab in CXCR4 mutated WM patients	Recruiting
NCT03620903	II	Single group, open-label study of first line bortezomib, rituximab and ibrutinib in treatment-naïve patients	Not yet recruiting
NCT03053440	III	Randomized, open-label, 1:1 study of BGB-3111 versus ibrutinib in WM	Active, not recruiting
NCT03679624	II	Non-randomized open-label study of ibrutinib+daratumumab in WM	Not yet recruiting
NCT02950220	I/Ib	Open-label, single group study of ibrutinib+pembrolizumab in relapsed/refractory non-Hodgkin lymphoma	Active, not recruiting
NCT02332980	II	Open-label, single group study of pembrolizumab alone or with idelalisib or ibrutinib in relapsed/refractory patients with CLL or low-grade B-cell non-Hodgkin lymphomas	Recruiting
NCT01955499	I	Open-label, single group study of ibrutinib+lenalidomide in relapsed/refractory B-cell non-Hodgkin lymphoma	Active, not recruiting
NCT03479268	I	Open-label, single group study of pevonedistat+ibrutinib in relapsed/refractory CLL or non-Hodgkin lymphoma patients	Recruiting
NCT01479842	I	Open-label, single group,dose-escalation trial of rituximab, bendamustine and ibrutinib in patients with relapsed non-Hodgkin lymphoma	Active, not recruiting

Abbreviations: CLL, chronic lymphocytic leukemia; WM, Waldenstrom’s macroglobulinemia.