DP047 | A SINGLE CENTER EXPERIENCE OF FIXED DURATION THERAPY IN 108 PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA

Background. The current treatment strategies for patients (pts) with chronic lymphocytic leukemia (CLL) include a continuous BTK inhibitor (BTKi) or a fixed-duration therapy (FDT) with combinations of target agents (BTKi and/or venetoclax [VEN] and/or antiCD20 monoclonal antibodies [mAb]). However, there are few data about the outcome of pts managed with FDT out of clinical trial. Aim. In this study we focused on the time to next treatment (TTNT) in treatment naive (TN) and relapsed/refractory (RR) pts with CLL who completed FDT. Methods. Electronic medical charts of pts followed at the Padua university hospital were reviewed to identify cases with CLL treated with FDT till Apr 15th, 2025. TTNT was calculated from the end of FDT to the beginning of the next line (event) or last known follow-up (censured). Survival curves were compared with the Logrank test. Results. 108 pts received a FDT (TN 69, RR 39), 58% were males (TN 57%, RR 67%), the median age at treatment was 65±12 yr (TN 62±12yr, RR 69±10yr), 67% showed IGHV unmutated (TN 64%, RR 82%), 19% TP53 abnormalities (TP53 abn [del17p and/or TP53 mutation], TN 14%, RR 25%) and 32% a complex karyotype (CK, TN 16%, RR 49%). The median line of previous therapy of RR pts was 1, range 1-7. 26% of TN pts received a BTKi+antiCD20 mAb, 35% VEN+antiCD20 mAb and 39% ibrutinib+VEN (I+V). While all RR pts received VEN+antiCD20 mAb. At data cut, 23 pts were still on treatment (TN 22, RR 1) and 18 discontinue FD therapy, 8 progressive disease (TN 1, RR 7) and 7 adverse events (TN 4 RR 3). Among pts available for response the ORR was 95% and 92%, including 53% and 58% of complete remissions, in TN and RR cases, respectively. 70 pts completed the FD therapy (TN 42, RR 28) and after a median follow-up of 30 months 14 pts (7 TN and 7 RR; 6 with TP53 abn and 9 with a CK) started a new therapy: 5 covalent BTKi, 3 no-covalent BTKi, 3 VEN+antiCD20 mAb and 3 investigational drugs. The median TTNT was not reached neither by TN nor RR pts. The estimated 3-yr TTNT was 91% and 75% of TN and RR pts. Although at subgroup analysis TP53 abn (HR 8.7, p=0.04) and CK (HR 9.1, p=0.002) impacted on TTNT only in TN but not in RR pts, their median TTNT was 37 months. Discussion. In this single center study, we pointed that FDT is feasible in most pts with CLL with only a few toxicity-related discontinuations, offering durable drug holiday periods. In the next future, MRD-driven treatment duration will likely further improve the management of our pts, in particular those with high-risk features.