OBINUTUZUMAB PLUS CHLORAMBUCIL VERSUS IBRUTINIB IN PREVIOUSLY UNTREATED PATIENTS WITH CHRONIC LYM- PHOCYTIC LEUKEMIA WITHOUT TP53 DISRUPTIONS. A CAMPUS CLL STUDY

Introduction:Although, Ibrutinib (IB) and obinutuzumab (G) have sig- nificantly improved the treatment landscape of chronic lymphocytic leukemia (CLL), no head-to-head comparison has been reported for IB vsG-chlorambucil (G-CHL) in CLL patients. Aim:The aim of this study was to compare the clinical efficacy of G- CHL and IB in a real-life retrospective study within the Italian CLL Cam- pus network. Methods: Patients received ibrutinib 420 mg daily until progression or unacceptable toxicity, while G was administrated at 100 mg on day 1, 900 mg on day 2 and 1000 mg on days 8 and 15 of the 1st cycle, then at 1000 mg for cycles 2-6. An IGHV gene sequence homology >98% was considered as unmutated (U-IGHV), as opposed to mutated (M-IGHV). Progression-free survival (PFS), time-to-next treatment (TTNT) and overall survival (OS) were compared with the log-rank test. Minimal residual disease (MRD), assessed by flow cytometry, was considered un- detectable when <10-4(uMRD4). A propensity score matching analysis 1:1 was also done, caliper 0.2. The study was approved by the Ethic Committee. Results:This study included patients without TP53 disruption who re- ceived IB (102 patients) or G-CHL at 16 hematologic centers till De- cember 2020. Clinical features of enrolled patients are summarized in Table 1. Patients in treated with G-CHL had a higher CIRS score (p=0.0015), lower creatinine clearance (p=0.0041) and were enriched in M-IGHV cases (p=0.0004). The best overall response rates in the G-CHL and IB arms were 87%vs77%, including 25%vs6% complete remis- sions (CR, p=0.0029). After a median follow-up of 30 months, the PFS, TTNT and OS was 70%vs93% (p=0.0061), 88%vs97% (p=0.0043) and 91%vs96% (p=0.6642) for the G-CHL and IB arms, respectively. In the G-CHL arm the depth of response in terms of iwCLL responses (No re- sponsevspartial remissionvsCR: 30-month PFS, 38%, 68% and 79%; p<0.0001) and responses with uMRD in the PB influenced PFS (data on 87 patients: 30-month PFS, 78%vs 53% for uMRD4vs MRD+, p=0.0203). PFS and TTNT were better with IB than G-CHL in U-IGHV (p=0.0190 and 0.0137, Figure 1A and 1C), while they were superimpos- able for M-IGHV patients (p=0.1900 and 0.1380, Figure 1B and 1D). Similar results were found after patients matching analysis. Conclusions:Although continuous ibrutinib provides a better disease control in CLL, M-IGHV patients and those achieving an uMRD4 show a marked clinical benefit from a fixed-duration obinutuzumab-based therapy.