C073 | PIRTOBRUTINIB IN RELAPSED OR REFRACTORY MANTLE CELL LYMPHOMA PATIENTS: OUTCOMES FROM THE COMPASSIONATE USE PROGRAM IN ITALY

Mantle cell lymphoma (MCL) presents a heterogeneous course with poor prognosis in relapsed/refractory (R/R) cases, particularly when therapy with covalent BTK-inhibitors (cBTK-i) fails. Pirtobrutinib, a reversible non-covalent BTK-i (ncBTK-i), has shown good tolerability and good efficacy in cBTK-i pre-treated patients with R/R MCL in a clinical trial, but real-world data are very limited. We retrospectively analyzed 40 patients with R/R MCL patients treated in 25 italian centers, within a compassionate use program between december 2022 and march 2024. Median time from MCL diagnosis to pirtobrutinib start was 4.7 years (1-23), and median number of prior lines was 3 (2-7). All patients had received prior cBTKi, with the majority of patients (87%) that had discontinued cBTKi because of progressive disease (PD). At the time of pirtobrutinib start median age of treated patients was 70 years (44-86), 88% were males, and 87% had high or intermediate Mantle Cell International Prognostic Index (MIPI). Twelve patients (30%) had blastoid or pleomorphic morphology, Ki67 was >30% in 74%, and 11 of 20 (55%) had TP53 mutation. After a median follow-up of 7 months (1-23), eight patients are still on active treatment. Overall response rate (ORR) to pirtobrutinib was 48%, with 25% of patients experiencing complete remission (CR), 23% that had partial response, 10% who had stable disease, and remaining 42% that had PD. Median progression-free survival (PFS) was 4.6 months, with seven patients that stopped the drug because of subsequent Car-T cell therapy and were censored at the time of infusion. For the 19 patients who achieved at least a PR, median duration of response (DOR) was not reached, with 65% of patients still in remission at one year (Figure 1). Duration of CR (DOCR) was even higher (78% at one year). Significant predictive factors for inferior DOR were elevated Ki67 (p=0.02), TP53 mutations (p=0.01), and POD24 since initial diagnosis to first relapse (p=0.03). Adverse events were rare and mild, with no patients that discontinued the drug due to toxicity. Conclusions: Our findings align with BRUIN trial results despite a population of very high risk R/R MCL patients, thus supporting the use of pirtobrutinib in this setting. Figure 1.