Pb1925: naos study: first interim analysis of acalabrutinib use in patients with chronic lymphocytic leukemia in a real-life setting.

Topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical Background: Treatment of Chronic Lymphocytic Leukemia (CLL) is based on the use of chemo-immunotherapies and targeted therapies. The approval of novel therapies in recent years, including acalabrutinib a next generation Bruton Tyrosine Kinase (BTK) inhibitor, has significantly changed the treatment of CLL (1,2). Real-life studies with acalabrutinib are needed to complement the data from the ELEVATE-TN, ASCEND and ELEVATE-RR clinical trials (3-5) and generate real-world evidence for its use in CLL. Aims: The objective of this first interim analysis is to describe baseline characteristics, disease characteristics and treatment patterns in CLL patients treated with acalabrutinib in first line (L1) and beyond (relapsed or refractory ≥L2). Methods: NAOS is a non-interventional, longitudinal study of CLL patients having initiated acalabrutinib in the labelled and reimbursed indications in 2021 and 2022, based on a retrospective data collection from medical records in 70 sites in France. The present analysis describes CLL adult patients who initiated acalabrutinib in 2021, at the first 25 active sites. Patient demographics, clinical characteristics and treatment patterns are described using descriptive statistics at baseline (acalabrutinib initiation), in the overall population and in the L1 and ≥ L2 sub-groups. Results: At data cutoff, 88 patients were enrolled of whom 59 patients initiated acalabrutinib in L1 (67.0%) and 29 (33.0%) in ≥L2 (16 patients in L2 and 13 in ≥L3). At acalabrutinib initiation, 61 patients were male (69.3%), median age was 73 and 78 years in the L1 and ≥L2 sub-groups respectively, [overall median age 74.5 years (IQR 70–80)], with 44 (50.0%) patients aged 75 years or older (table 1). Fourteen (20.3%) patients had an ECOG ≥2. Binet stage (at acalabrutinib initiation) was A, B and C in 25.4%, 33.9% and 40.7% patients, respectively. Forty-one patients (47.7%) had cardiovascular history and 32 patients (37.2%) had hypertension. Hemoglobin rate was ≤ 110 g/L in 45.2% patients, platelet count was ≤ 100 G/L in 25.0% patients and neutrophils count ≤1.5 G/L in 7.6% patients. Creatinine clearance was < 60 mL/min in 32.4% patients. Chromosome del(17p) was present in 20% (13/65) patients, mutated TP53 in 22.7% (15/66) patients, del(17p) and/or TP53 in 23.2% patients with 13.8% in L1 and 45.8% in ≥L2, del(11q) in 31.0% (18/58) patients, unmutated IGVH in 65.3% (32/49) patients and complex karyotype in 35.7% (20/56) patients. Median time from CLL diagnosis to acalabrutinib initiation was 2.7 years (IQR 1.1 – 6.2) in L1 and 8.2 years (IQR 5.2-11.3) in ≥L2. Among the 29 patients in ≥L2, previous therapies included bendamustine and rituximab (36.0%), fludarabine, cyclophosphamide, rituximab (FCR, 32.0%), ibrutinib (20.0%), chlorambucil and rituximab (16.0%) or chlorambucil (20.0%). L1 patients received acalabrutinib monotherapy (61.0%) and as combination (39.0%), mostly with obinutuzumab. Acalabrutinib was used in monotherapy in most ≥L2 patients (93.1%). 89.8% of patients (93.2% in L1 and 82.8% in ≥L2) were on standard 100mg BID dosing regimen. Summary/Conclusion: The NAOS study is one of the first real-life descriptions of patients receiving acalabrutinib in Europe. In this first analysis, most patients received acalabrutinib as first-line therapy. Acalabrutinib was used in patients older than in the published phase III clinical trials, with more frailties (ECOG, creatinine clearance) and cardiovascular risks. High cytogenetic risk (del17p and/or TP53 mutation) was documented in 23.2% patients who initiated acalabrutinib in 2021. Keywords: Chronic lymphocytic leukemia