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Preliminary Results of the Filo Phase 2 Trial for Untreated Fit Patients with Intermediate Risk Chronic Lymphocytic Leukemia Comparing Ibrutinib Plus Venetoclax (IV) Versus FCR
Blood ; 138:641, 2021.
Article in English | EMBASE | ID: covidwho-1582424
ABSTRACT
With the emergence of targeted therapies, defining the best strategy for the treatment of previously untreated CLL patients remains challenging. The aim of this phase 2 study was to compare the efficacy of an association with ibrutinib and venetoclax (IV) to the standard FCR regimen in fit patients with intermediate risk CLL defined by either unmutated IGHV status, 11q deletion or complex karyotype in the absence of TP53 abnormality. Patients were randomized 11 between two treatment arms, ie FCR 6 cycles or IV. After a lead-in phase of ibrutinib as a single agent from month (M)1 to M3, the total duration of treatment with IV was based on the response achieved at M9;if bone marrow (BM) MRD was < 0.01% using flow cytometry, the treatment was continued for 6 additional months until M15 and then stopped;if BM MRD at M9 was ≥ 0.01%, the treatment with IV was continued for 18 additional months until M27. The primary endpoint was the percentage of patients with BM MRD < 0.01% at M27 in both arms. We present here the preliminary results on the first evaluation done at M9 including CT-scan, BM biopsy and MRD assessment in PB and BM after the inclusion of all the 120 patients as initially planned. One hundred and twenty patients were enrolled from September 2019 to February 2021. The median age was 59 [34-72] and 61 [34-74] years in the FCR and IV arms, respectively. The characteristics of the patients were well balanced between the 2 arms in terms of gender (male 72% FCR, 74% IV), PS ECOG 0-1 (59% FCR, 68% IV) and Binet stage (A, B and C 15%, 64%, 21% for FCR;8.5%, 59% and 32% for IV). No major difference in terms of cytogenetic features was noted, all patients but one had unmutated IGHV. At the time of data cut-off for this interim analysis, the median follow-up for the all cohort was 11 [2.9 - 19.8] months. The frequency of all grades adverse events (AE) observed so far was 53% (grade 3-4, 24%) in the FCR arm and 47% (grade 3-4, 17%) in the IV arm. The rate of infusion-related reactions (IRR) in the FCR arm was 35% on cycle 1-day 1 (14% grade 3-4);for the IV arm, 6% of patients experienced tumor lysis syndrome (TLS) (grade 4 for 4 patients). ibrutinib doses were reduced for 7 patients (4 permanently stopped and 3 resumed at a lower dose because of toxicities (digestive, hepatic or haematological)). Venetoclax was permanently discontinued before M9 in 4 patients (digestive toxicities and grade 4 neutropenia). Forty serious adverse events were reported of which 15 in the IV arm (1 sudden death, 1 ischemic stroke, 2 atrial fibrillations, 2 clinical TLS, 1 hepatitis, 1 neutropenia, 4 COVID pneumonitis and one osteoporotic fracture) and 25 in the FCR arm (2 neutropenias, 1 anemia, 1 thrombocytopenia, 1 autoimmune haemolytic anemia, 3 IRR, 4 TLS, 2 COVID pneumonitis, 4 fever episodes of undetermined origin, 1 community-acquired pneumonia, 1 gastrointestinal toxicity, 1 confusion, 2 chest pains, 1 acute myeloid leukemia, 1 myelodysplasic syndrome). The patients with COVID pneumonitis had a favorable evolution with the need for intensive care and convalescent plasma for 3 of them. The first 60 patients included in the study have reached M9 and among them, 6 prematurely discontinued the study, 3 in each arm (active hemolysis, ischemic stroke and sudden death in the IV arm;2 grade 4 hematologic toxicities and 1 early progression in the FCR arm). In the evaluated patients (n=54), 71% of patients in the FCR arm and 48% of patients in the IV arm achieved bone BM MRD < 0.01%. The complete (CR, CRi) and partial response rates were 54% and 46% in the FCR arm and 76% and 24% in the IV arm respectively. In conclusion, the preliminary results show a lower BM MRD rate in the IV arm compared to the FCR arm at M9, with a toxicity that remains significant and relatively similar between the two arms. However, BM MRD rate should improve after longer exposure to the IV combination and the analysis of the primary endpoint at M27 will be decisive in determining the best therapeutic strategy. Disclosures Quinquenel Abbvie Honoraria;Jansse Honoraria;AstraZeneca Honoraria. Laribi Le Mans Hospital Research Funding;Novartis Other Personal Fees, Research Funding;Takeda Other Personal Fees, Research Funding;BeiGene Other Personal Fees;IQONE Other Personal Fees;AbbVie Other Personal Fees, Research Funding;Astellas Phama, Inc. Other Personal Fees;AstraZeneca Other Personal Fees;Jansen Research Funding. Cymbalista Lilly-LOXO Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen Honoraria, Membership on an entity's Board of Directors or advisory committees;ASTRA ZENECA Honoraria, Membership on an entity's Board of Directors or advisory committees;Abbvie Honoraria, Membership on an entity's Board of Directors or advisory committees;Roche Honoraria, Membership on an entity's Board of Directors or advisory committees. Leblond AstraZeneca Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees;Lilly Consultancy;AbbVie Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other Travel Support;Roche Honoraria;Amgen Honoraria;Beigene Honoraria, Membership on an entity's Board of Directors or advisory committees;Janssen Honoraria, Membership on an entity's Board of Directors or advisory committees. Dartigeas Astra-Zeneca Membership on an entity's Board of Directors or advisory committees, Other travel grants/Congress;Abbvie Membership on an entity's Board of Directors or advisory committees, Other travel grants/Congress;Janssen Membership on an entity's Board of Directors or advisory committees, Other travel grants/Congress. Ferrant Janssen Other Travel, Accommodations, Expenses;AbbVie Honoraria, Other Travel, Accommodations, Expenses;AstraZeneca Honoraria. de Guibert Janssen Consultancy, Honoraria;AbbVie Consultancy, Honoraria;Gilead Consultancy, Honoraria. Feugier Astrazeneca Consultancy, Honoraria;Gilead Consultancy, Honoraria;Abbvie Consultancy, Honoraria;Amgen Honoraria;Janssen Consultancy, Honoraria. Cartron Roche, Celgene-BMS Consultancy;Danofi, Gilead, Novartis, Jansen, Roche, Celgene-BMS, Abbvie, Takeda Honoraria. Ysebaert Abbvie, AstraZeneca, Janssen, Roche Other Advisory Board, Research Funding.
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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Prognostic study / Randomized controlled trials Language: English Journal: Blood Year: 2021 Document Type: Article

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Full text: Available Collection: Databases of international organizations Database: EMBASE Type of study: Prognostic study / Randomized controlled trials Language: English Journal: Blood Year: 2021 Document Type: Article