BTK inhibitors: safety plus efficacy = outcome

In the current issue of Blood, Seymour et al1 report the adverse event (AE) burden of continuous acalabrutinib versus ibrutinib treatment in the previously reported phase 3 randomized trial ELEVATE-RR for chronic lymphocytic leukemia (CLL).2 Approved covalent Bruton tyrosine kinase (BTK) inhibitors like ibrutinib and acalabrutinib have changed the treatment paradigm for CLL. This article emphasizes that the significant improvement in treatment options for CLL during the last decade raises important questions about the differences in risk-benefit for the different treatment options and for different subgroups of patients. These questions can be generalized and applied to treatment of hematological diseases as follows: (1) can we directly compare efficacy in terms of progression-free survival (PFS) between treatments of different lengths, (2) can we directly compare AEs by frequency and grade for treatments of different lengths, (3) can we assess efficacy as a primary outcome without taking discontinuation rates and safety profiles into account, and (4) can we combine measures such as the AE burden score applied by Seymour et al with efficacy assessment to weigh different good treatment options against each other?

Automated summary

This study compares the adverse event burden of continuous acalabrutinib versus ibrutinib treatment in CLL. The improved treatment options for CLL in recent years have raised important questions about risk-benefit differences between different treatment options and patient subgroups.