Clinical Approaches in Switching Between BTKi’s in R/R CLL & Practical Considerations for Drug Holidays

Cross-Class BTK Inhibitor Switching and Clinical Evidence

Phase 2 clinical trials have demonstrated the feasibility and efficacy of switching between different covalent BTK inhibitors in patients with drug-specific intolerances. Studies switching from ibrutinib to acalabrutinib showed that 60-70% of patients did not experience recurrence of their original intolerance while maintaining therapeutic responses. Similar results were observed with zanubrutinib switches, where the majority of patients with ibrutinib or acalabrutinib intolerances successfully transitioned without experiencing their previous toxicities. These studies confirm that drug-specific intolerances often don't recur with alternative covalent BTK inhibitors, though new side effects may develop. Clinical experience supports the off-label practice of cycling through different BTK inhibitors to manage intolerances while maintaining patients on effective targeted therapy. This approach extends treatment duration and delays the need for alternative drug classes, which is particularly important for long-term disease control in a chronic condition like CLL.