ABSTRACT BTK inhibitors (BTKi) have reshaped the therapeutic algorithm of lymphoproliferative diseases, but class‐specific adverse events (AEs) have emerged. Dose adjustment (DA) is often attempted to mitigate AEs, particularly with ibrutinib, the first BTKi approved for relapsed/refractory (R/R) mantle cell lymphoma (MCL) patients. We described ibrutinib DA in 226 consecutive R/R MCL who started ibrutinib between 2016 and 2023. We assessed DA rate and calculated single patient's relative ibrutinib dose as a percentage of the expected full dose during the entire treatment period, grouping patients into 4 dose levels (DL1a 95%–100%, DL1b 75%–94%, DL2a 50%–74%, DL2b < 50%). We evaluated changes in response, progression free survival (PFS), overall survival (OS) and time to next treatment (TTNT) between groups. Thirty‐four percent of patients started ibrutinib at reduced dose, mainly due to age/comorbidities. Overall, 44% of patients reduced ibrutinib dose, mostly due to AEs. Thirty‐five percent of patients interrupted treatment, predominantly for AEs, and 65% of patients discontinued ibrutinib, most often due to progressive disease (70%). No statistically significant differences in response rates/PFS/OS were observed across DLs. Interestingly, patients on the lowest dose tended to remain on treatment longer. This is the first real‐life report evaluating ibrutinib DA in MCL. We showed that DA is common, particularly in older comorbid patients, and doesn't compromise efficacy, making it a feasible strategy for managing ibrutinib‐related toxicities.
Quaglia et al. (Thu,) studied this question.