P001 | IBRUTINIB DOSE MODIFICATION IN MANTLE CELL LYMPHOMA: AN ITALIAN REAL-LIFE MULTICENTER EXPERIENCE. RESULTS FROM THE REDOT_MCL STUDY.

BTK inhibitors (BTKi) have reshaped the therapeutic algorithm of lymphoproliferative diseases, but class-specific adverse events (AEs) such as bleeding, atrial fibrillation and cytopenia emerged. Dose modification (DM) is often attempted to mitigate AEs, particularly with ibrutinib, the first BTKi approved for relapsed/refractory (R/R) mantle cell lymphoma (MCL). The REDOT study described ibrutinib DM in R/R MCL from 14 Italian centers, evaluating DM impact on outcomes. We assessed DM rate in a real-life series of MCL patients who started ibrutinib between 2016 and 2023. We calculated single patient’s relative cumulative ibrutinib dose as a percentage of expected full dose during the entire treatment period. Patients were grouped into 4 dose levels (DL1a 95-100%, DL1b 75-94%, DL2a 50-74%, DL2b <50%). We evaluated ibrutinib-related AEs, changes in response and PFS/OS/TTNT between groups. We included 226 consecutive patients with median age 73 years at ibrutinib start. Overall, 34% of patients started ibrutinib at reduced dose, in most cases (67%) due to age or comorbidities, concomitant therapies (16%), cytopenia (9%) or unknown reason (9%). Forty-four percent of patients reduced ibrutinib either at start or during treatment. Median time to first reduction was 5 months. In 73% of cases reductions were caused by AEs. Thirty-five percent of patients interrupted ibrutinib, due to AEs (65% of interruptions), surgical procedures or patient choice (35%). Sixty-five percent of patients permanently discontinued ibrutinib due to progressive disease (70%), AEs or other reasons (15% each) including allo-SCT. Overall, 54% and 15% of patients were grouped into DL1a and 1b, 22% and 9% into DL2a and 2b, respectively. No statistically significant difference in response rates emerged between the 4 DLs (p=0.516; Fig1A). We showed similar 3y-PFS (DL1a 25%, 1b 40%, 2a 30%, 2b 36%, p=0.426; Fig1B). Accordingly, there was no statistically significant difference in 3y-OS (DL1a 42%, 1b 45%, 2a 37%, 2b 51%, p=0.657). Contrarily regarding TTNT, DL2b patients tended to stay in treatment longer than those who took higher doses (p=0.058). This is the first report evaluating ibrutinib DM in a real-life MCL setting. We showed higher DM rates than in clinical trials, probably due to advanced age and comorbidities. Since ibrutinib dose did not significantly impact responses and outcomes, DM is a viable strategy especially for elderly MCL patients with comorbidities or drug-related AEs.