Guide for selecting BTKis for the treatment of WM
| . | Preference . | Alternative . |
|---|---|---|
| BTKi options for initial therapy | ||
| Convenience/compliance | Ibrutinib Zanubrutinib∗, Tirabrutinib∗ | Acalabrutinib |
| Deep IgM response needed (ie, IgM demyelinating neuropathy, cryoglobulinemia, and cold agglutinemia) | Zanubrutinib† | Ibrutinib Acalabrutinib Tirabrutinib‡ |
| BNS | Ibrutinib Tirabrutinib‡ | Zanubrutinib |
| History or predisposition to arrythmia | Zanubrutinib§ | |
| History or predisposition to bleeding | Zanubrutinib§ | |
| Neutropenic or pancytopenic | Ibrutinib | |
| MYD88WT | Zanubrutinib | |
| CXCR4Mut | Zanubrutinib | Ibrutinib plus rituximab |
| TP53 alteration | Zanubrutinib | Ibrutinib |
| BTKi options for switchover | ||
| Intolerant to ibrutinib for adverse events other than atrial fibrillation | Dose-reduction of Ibrutinib Zanubrutinib Acalabrutinib‖ | Pirtobrutinib¶ |
| Intolerant to ibrutinib due to atrial fibrillation | Zanubrutinib | Pirtobrutinib¶ |
| Acquired resistance to a cBTKi | Pirtobrutinib |
| . | Preference . | Alternative . |
|---|---|---|
| BTKi options for initial therapy | ||
| Convenience/compliance | Ibrutinib Zanubrutinib∗, Tirabrutinib∗ | Acalabrutinib |
| Deep IgM response needed (ie, IgM demyelinating neuropathy, cryoglobulinemia, and cold agglutinemia) | Zanubrutinib† | Ibrutinib Acalabrutinib Tirabrutinib‡ |
| BNS | Ibrutinib Tirabrutinib‡ | Zanubrutinib |
| History or predisposition to arrythmia | Zanubrutinib§ | |
| History or predisposition to bleeding | Zanubrutinib§ | |
| Neutropenic or pancytopenic | Ibrutinib | |
| MYD88WT | Zanubrutinib | |
| CXCR4Mut | Zanubrutinib | Ibrutinib plus rituximab |
| TP53 alteration | Zanubrutinib | Ibrutinib |
| BTKi options for switchover | ||
| Intolerant to ibrutinib for adverse events other than atrial fibrillation | Dose-reduction of Ibrutinib Zanubrutinib Acalabrutinib‖ | Pirtobrutinib¶ |
| Intolerant to ibrutinib due to atrial fibrillation | Zanubrutinib | Pirtobrutinib¶ |
| Acquired resistance to a cBTKi | Pirtobrutinib |
Preferences are based on availability and weight of clinical data supporting the use of a particular BTKi for a select patient and represent the viewpoint and experience of the authors. Supporting data for these recommendations are presented in the text. Listed BTKis are approved for WM and/or other indications in any jurisdiction. Clinicians should consult local regulatory approvals and guidelines for their status and use in WM.
Zanubrutinib is approved for use as single (320 mg) daily or twice-daily (160 mg) administration.
ASPEN data demonstrating a higher VGPR rate for zanubrutinib vs ibrutinib is based on twice-daily administration of zanubrutinib.
Tirabrutinib is only approved in Japan. No randomized data against any other cBTKi.
ASPEN data demonstrating a lower risk of atrial fibrillation and bleeding diathesis for zanubrutinib vs ibrutinib is based on twice-daily administration of zanubrutinib.
Switchover data supported by a study with patients with chronic lymphocytic leukemia (as previously reported69).
Safety data for use in WM remain limited. Alternatives to BTKis for patients who are intolerant or those with acquired resistance to BTKis are presented in the text.