Table 2.
Clinical trials of novel BTK inhibitors in WM patients.
| Patients (n) | Design/disease setting | Treatment | Outcomes | Comments | |
|---|---|---|---|---|---|
| Trotman et al.102, 2020103; Tam et al.101 | 77 (24 TN; 53 RR) | Phase I/II prospective | PO zanubrutinib | ORR: 96% VGPR/CR: 45.2% 3-year PFS: 80.5% 3-year OS: 84.8% |
VGPR/CR rate increased over time: 20.5% at 6 months, 32.9% at 12 months, and 43.8% at 24 months AEs of interest: contusion (32.5%, grade 1), neutropenia (18.2%), major hemorrhage (3.9%), atrial fibrillation/flutter (5.2%), grade 3 diarrhea (2.6%) |
| Tam et al.104; Garcia-Sanz et al.105 | 201 MYD88L265P (cohort 1) 26 MYD88WT (cohort 2) |
Phase III prospective, randomized (cohort 1) | PO zanubrutinib versus ibrutinib (cohort 1), PO zanubrutinib (cohort 2) | Cohort 1 VGPR/CR: 28.4% versus 19.2% ORR: 78% versus 78% MRR: 77.5% versus 77.8% 18-month PFS: 85% versus 84% Cohort 2 VGPR:26.9% ORR: 80.8% MRR: 50% 12-month PFS: 72.4% |
Incidence of atrial fibrillation, contusion, diarrhea, peripheral edema, hemorrhage, muscle spasms, and pneumonia, as well as adverse events leading to treatment discontinuation, were all lower among zanubrutinib recipients; incidence of neutropenia was higher with zanubrutinib, although grade 3 or higher infection rates were similar in both groups |
| Owen et al.106 | 106 (14 TN, 92 RR) | Phase II, prospective | PO acalabrutinib | ORR: 93% MRR: 78% 24-month PFS: 90% TN, 82% RR |
Common AEs: headache, diarrhoea, bruising, fatigue, nausea, arthralgia Most common grade 3 (or higher) AEs: neutropenia and lower respiratory tract infections Atrial fibrillation: 5% MYD88 wild type (n = 14): PR rate = 64% |
| Sekiguchi et al.107 | 27 (18 TN, 9 RR) | Phase II, prospective | PO tirabrutinib | TN: ORR, 94.4%, MRR, 88.9% RR: ORR, 100%, MRR, 88.9% Median PFS and OS not reached |
96.2% MYD88L265P mutated Most common AEs: rash (44.4%), neutropenia (25.9%), leukopenia (22.2%) Grade ⩾3 AEs: neutropenia (11.1%), lymphopenia (11.1%), leukopenia (7.4%) |
AEs, adverse events; BTK, Bruton’s tyrosine kinase; CR, complete remission; MRR, major response rate; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PO, per os (orally); RR, relapsed/refractory; TN, treatment naïve; VGPR, very good partial response; WM, Waldenström’s macroglobulinemia.