P112 | REAL-WORLD OUTCOME OF PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA TREATED WITH BTK INHIBITORS WHO DISCONTINUED TREATMENT FOR REASONS OTHER THAN DISEASE PROGRESSION: EXPERIENCE FROM PIEDMONT CENTERS

Background: The advent of Bruton's tyrosine kinase inhibitors (BTKi) has revolutionized the treatment of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). BTKi are administered continuously until progression or unacceptable toxicity. Failure of BTKi treatment is primarily due to toxicity and selection of resistance mutations. Recently, fixed-duration regimens (I+V and VO) have been developed and approved, offering a strategy to limit drug exposure and prevent resistance. Outcomes of patients discontinuing therapy for reasons other than progression may provide insights into what happens with fixed-duration BTKi. Patients/Methods: To assess the outcome of patients who discontinued BTKi therapy for reasons other than progression, we collected data from 18 patients treated with BTKi between January 2014 and January 2025 (17 Ibrutinib, 2 Acalabrutinib) across 4 centers. We included patients treated with BTKi for at least one year and then discontinued therapy for at least 6 months. Primary objective was Time to Next Treatment (TTNT), secondary objectives were median PFS e OS. Results: Median age was 78 (62-87) years. Molecular data were available for 15 patients: 7 had unmutated IGHV and 8 had TP53 aberrations. Median number of prior lines of therapies was 1 (0-5). Median treatment duration prior to discontinuation was 28.4 months. Cumulative incidence of restarting treatment, with death as a competing risk, was 6.25% (1/16) at 12 months, 25% (2/8) at 24 months, 66.6% (4/6) at 36 months, and 83.3% (5/6) at 48 months. Median TTNT was 28.5 months. Notably, in most cases the duration of the treatment with BTKi matched the TTNT, suggesting that long-term BTKi exposure may allow for sustained treatment-free intervals. Moreover, among 6 patients who underwent retreatment, 5 received BTKi therapy, achieving a partial response or better. Of the 5 patients with available molecular data, all had high-risk characteristics (U-IGHV or TP53 aberrations). PFS and OS were not reached. Conclusion: These findings suggest that continuous therapy with BTKi may not be always necessary and that in selected cases, intermittent treatment could ensure durable disease control. Fixed-duration BTKi therapy could provide several advantages, such as minimizing long-term side effects and costs, while potentially preventing the development of resistance mechanisms. Certainly, prospective studies are warranted to further explore this approach.