Zanubrutinib in the treatment of Waldenström Macroglobulinemia
Zanubrutinib is more selective for BTK than other structurally related kinases and is better tolerated with lower rates of discontinuation compared with ibrutinib.
Waldenström Macroglobulinemia (WM) is a rare B‑cell lymphoma characterized by IgM‑secreting lymphoplasmacytic cells. MYD88 mutations occur in >90% of cases, while CXCR4, KMT2D, ARID1A, TERT, and TP53 mutations are also frequently detected. The Bruton tyrosine kinase inhibitor ibrutinib demonstrated activity in WM but was limited by off‑target toxicity. Second‑generation B‑TKIs, zanubrutinib and acalabrutinib, offer greater selectivity for BTK and a more favorable safety profile. In WM, zanubrutinib has shown superior efficacy to ibrutinib in MYD88‑wild‑type, CXCR4‑mutated, or TP53‑mutated patients, yet CXCR4 and TP53 mutations still predict poorer outcomes compared with mutation‑negative cases. Combining BTK inhibition with other agents and ongoing trials aim to address resistance and improve outcomes for patients with WM.
Because improved selectivity and tolerance of zanubrutinib translate into deeper, longer‑lasting responses and fewer adverse events for patients with Waldenström macroglobulinemia, potentially allowing broader use of BTK inhibitors in this disease.
Bizonyítékszint: Korai humán adat. Kis vagy feltáró emberi adat.
Kapcsolódó jelek
- Waldenström Macroglobulinemia Clinical Trials
- European Consortium for Waldenström's Macroglobulinemia
- Waldenström Macroglobulinemia - A State-of-the-Art Review: Part 2- Focus on Therapy
- The therapeutic perspective of relapsed/refractory Waldenström Macroglobulinemia: what comes next?
- Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström's Macroglobulinemia