ASPEN (Waldenström macroglobulinaemia)

ASPEN randomised 201 patients with MYD88-mutated Waldenström macroglobulinaemia to zanubrutinib or ibrutinib, the first head-to-head comparison of BTK inhibitors in any disease. The primary endpoint was the rate of complete or very good partial response. A third, non-randomised cohort treated MYD88 wild-type patients with zanubrutinib.

The rate of complete or very good partial response was numerically higher with zanubrutinib but the difference was not statistically significant, so the primary endpoint was not met. Zanubrutinib caused substantially less atrial fibrillation, bleeding, diarrhoea and hypertension, and fewer patients stopped it for toxicity. On the strength of efficacy and tolerability it was approved in the United States for Waldenström macroglobulinaemia in 2021. Not to be confused with the ASPEN trial of everolimus versus sunitinib in non-clear-cell kidney cancer.