C014 | EFFICACY AND SAFETY OF IBRUTINIB AS SECOND-LINE TREATMENT IN RELAPSED/REFRACTORY MANTLE CELL LYMPHOMA: INTERIM ANALYSIS OF THE OLIMPUS STUDY

Introduction: Mantle cell lymphoma (MCL) is an incurable disease characterized by an aggressive clinical course. Ibrutinib has been approved for relapsed/refractory (R/R) MCL and rapidly became standard therapy in the second-line setting. Several studies have reported results with ibrutinib in R/R MCL, but real-world data are limited. Materials and methods: We conducted a prospective study, which enrolled 106 patients with first R/R MCL in 34 Italian centers. The primary objective was overall response rate (ORR) according to Lugano criteria. We present data for a pre-planned interim analysis on 51 patients, who had a minimum observation time of 12 months after ibrutinib start. Results: Median age at enrollment was 71 years (range 35-90), and most patients were male (68.6%). At MCL initial diagnosis, sMIPI score was high in 31%, and 28% were refractory to first-line treatment, with median time to first relapse of 12.7 months (range 1.3 – 190.3). Blastoid/pleomorphic histology was observed in 7.8% of the cohort, while a TP53 mutation was identified in 50% of the tested patients (6/12). Ibrutinib was started at a median dose of 512 mg (140-560 mg). At Month 12 (±4 weeks), 44 patients had at least one response evaluation, resulting in an ORR of 73%, with 18 (41%) patients achieving complete response. Stable disease was recorded in 5 patients (11%), and four (9%) experienced progressive disease. After a median follow-up of 11.6 months, the progression-free survival was 73.9% (95% CI: 57.8-84.7) and the overall survival was 90.5% (95% CI: 76.6-96.3). In the safety analysis population, 18 patients (35%) discontinued ibrutinib by month 12 for any reason, resulting in a cumulative 1-year probability of being still on active therapy of 62.7% (95% CI: 47.4-74.8). Adverse events (AE) were reported in 34 patients (67%), being of grade 3-4 in 10 (20%). Most frequent adverse events were infections (14, 28%), followed by cardio-vascular disorders, which occurred in 9 patients (18%). Conclusions: In conclusion, ibrutinib has proven to be an effective and safe treatment option for patients with R/R MCL in a real-world clinical setting. These findings are consistent with those observed in clinical trials and provide additional support for its role as standard of care in second-line treatment. The final analysis will examine the comprehensive results of the study across the entire cohort, assessing the influence of key prognostic factors and drug discontinuation on patient outcomes.