Zanubrutinib in Waldenström Macroglobulinemia

The unblinded multicenter phase III ASPEN study (ClinicalTrials.govidentifier: NCT03053440) compared the safety and efficacy of zanubrutinib with that of ibrutinib in advanced Waldenstr öm macroglobulinemia. 1 We raise some concerns regarding the recently published 44-month ASPEN follow-up, which we hope the authors might address.The first concern is the changing ibrutinib response rates in consecutive studies.2][3] We admit it is inappropriate to compare results from different studies when one cannot adjust for latent and unknowable predictive covariates or for chance.However, we note that the median number of prior therapies of patients receiving ibrutinib in the PCYC-1118 study was 2 (1-9), and 43% received ≥3, whereas the median number of prior therapies of patients receiving ibrutinib in the ASPEN study was 1 (0-6), and only 25% received ≥3.In patients in the MYD88 mut /CXCR4 WT cohort in the PCYC-1118E study, the ≥VGPR rate was 44% (28%-62%) compared with 31% (20%-42%) in seemingly similar patients receiving ibrutinib in the ASPEN study.