Ibrutinib Dose Adjustment Does Not Impair Treatment Outcome in Mantle Cell Lymphoma: An Italian Real-Life Multicenter...

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.