Ibrutinib
First-generation BTK inhibitor
- Response rate
- 90% ORR; 73% MRR (previously treated)
- Onset
- Weeks (median 4 weeks to minor response)
- Route
- Oral 420mg daily
- Line
- 1st
- IgM effect
- Significant reduction
Evidence summary
First BTK inhibitor approved for WM. Directly targets MYD88-BTK-NF-kB axis. Response depends on genotype: MYD88mut/CXCR4wt patients achieve 100% ORR, while CXCR4-mutated and MYD88-WT patients have lower responses. Notable side effects include atrial fibrillation, hypertension, and bleeding. Also uniquely relevant in Schnitzler syndrome where it targets both inflammation and IgM.
Molecular targets (2)
| Molecule | Role | Expression | Evidence |
|---|---|---|---|
| MYD88 | Central oncogenic driver (TLR/IL-1R adaptor) | L265P gain-of-function in >90% | established |
| BTK (Bruton's Tyrosine Kinase) | Key signaling kinase downstream of MYD88 | Constitutively activated | established |