P676: LOW-DOSE FCR COMPARED TO BR IN PREVIOUSLY UNTREATED PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA WITHOUT TP53 ABERRATIONS: A REAL – WORLD RETROSPECTIVE ANALYSIS BY THE CZECH CLL STUDY GROUP.

Abstract

Background: Low – dose fludarabine, cyclophosphamide, and rituximab (LDFCR) regimen showed promising activity in treatment-naïve elderly / comorbid patients (pts) with chronic lymphocytic leukemia (CLL) (Smolej et al., Br J Haematol. 2021). However, no data are available regarding comparison to bendamustine and rituximab (BR), which has been one of the predominant first - line options for CLL patients ineligible for full – dose FCR. Aims: To perform a historical comparison of the efficacy and safety of LDFCR and BR regimens used as the first - line therapy of CLL within routine practice. Patients with 17p deletion and/or TP53 mutation were not included in this analysis because chemoimmunotherapy is no longer indicated in this extremely unfavourable subgroup due to very low activity. Methods: The analysis included 237 pts treated with LDFCR and 320 pts treated with BR (median age, 69 vs 70 years; males, 70 vs 61%; median CIRS score, 6 vs 7; Rai stage III/IV, 57 vs 59%; bulky lymphadenopathy > 5cm, 35 vs 35%; unmutated IGHV, 74 vs 70%, deletion 11q, 28 vs 26%) treated between March 2009 and December 2019 at 17 centers cooperating within the Czech CLL Study Group. LDFCR consisted of fludarabine 20 mg/m2 orally or 12 mg/m2 on days 1-3, cyclophosphamide 150mg/m2 orally or iv on days 1-3, and rituximab 500 mg/m2 D1 (375 mg/m2 in Cycle 1). BR included bendamustine 90 mg/m2 iv on days 1-2 and rituximab 500 mg/m2 D1 (375 mg/m2 in Cycle 1). Median follow – up was 98 months for LDFCR and 57 months for BR. Results: Distribution of demographic data and prognostic factors was comparable between LDFCR and BR groups. The overall response rate / complete remissions were similar for LDFCR vs BR (84/46% vs. 88/51%, p=n.s.). The median progression – free survival (PFS) was 30 vs 34 months (hazard radio [HR] 0.90; p=n.s.); PFS was markedly longer in pts with mutated IGHV and absence of del 11q (LDFCR vs BR, median 58 vs 59 months, HR 0.84; p=n.s.; Fig. 1a). Median overall survival (OS) was 73 vs 77 months for LDFCR vs BR (HR 1.09; p=n.s.) but markedly longer (median 116 months vs not reached) in patients with mutated IGHV without del 11q (HR 0.90; p=n.s.; Fig. 1b). Grade ≥ 3 neutropenia occurred in 55% (LDFCR) vs 51% (BR) pts but serious infections developed in 15% vs 20% pts only. Image:Summary/Conclusion: Our data indicate that both low-dose FCR and BR are well – tolerated regimens with similar efficacy and safety and represent a suitable first - line treatment alternative for elderly / comorbid CLL patients with favourable biological prognosis. Detailed results including multivariate analysis will be presented.