Session: 642. CLL: Therapy, excluding Transplantation: Poster III
Hematology Disease Topics & Pathways:
Biological, Adult, survivorship, Diseases, Therapies, Combinations, enzyme inhibitors, white blood cells, Cell Lineage, Lymphoid Malignancies, Study Population, Clinically relevant, Quality Improvement , TKI
Methods: In this randomized, multicenter, phase 3, open-label study (NCT02970318), patients with R/R CLL were randomized 1:1 to receive oral (PO) acala 100 mg twice daily (BID) or investigator’s (INV) choice of IdR (Id: 150 mg PO BID until progression or toxicity; R: 375 x1 then 500 mg/m2 intravenously [IV] for 8 total infusions) or BR (B: 70 mg/m2 IV and R: 375 x1 then 500 mg/m2 IV for 6 total cycles) until progression or toxicity. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed.
Results: 310 patients (acala, n=155; IdR, n=119; BR, n=36) were enrolled (median age: 67 y; del(17p) 16%, del(11q) 27%, Rai stage 3/4 42%). At a median follow-up of 22.0 m, acala significantly prolonged INV-assessed PFS vs IdR/BR (median: not reached vs 16.8 m; hazard ratio: 0.27, P<0.0001); 18-m PFS rates were 82% for acala and 48% for IdR/BR. 18-m OS rate was 88% for both treatment regimens. ORR was 80% with acala vs 84% with IdR/BR (ORR + partial response with lymphocytosis: 92% vs 88%, respectively). Common adverse events (AEs) are listed in the Table. AEs led to drug discontinuation in 16% of acala, 56% of IdR, and 17% of BR patients. AEs of interest included atrial fibrillation (acala 6%, IdR/BR 3%), major hemorrhage (all grade; acala 3%, IdR/BR 3%), grade ≥3 infections (acala 20%, IdR/BR 25%), and second primary malignancies excluding non-melanoma skin cancer (acala 5%, IdR/BR 2%).
Conclusions: Final ASCEND results with additional follow-up confirm earlier findings and support the favorable efficacy and safety of acala compared with standard-of-care regimens in patients with R/R CLL.
Disclosures: Ghia: Novartis: Research Funding; ArQule: Consultancy, Honoraria; Acerta/AstraZeneca: Consultancy, Honoraria; Adaptive, Dynamo: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Research Funding; BeiGene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Celgene/Juno: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; MEI: Consultancy, Honoraria; Sunesis: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding. Pluta: Janssen-Cilag, Kartos Therapeutics, Iqvia, Roche, Acerta Pharma, Pharmacyclics, BeiGene, Takeda: Research Funding; Celgene, Servier, Takeda, Novartis: Honoraria; Celgene: Other: Travel, Accommodations, Expenses. Lysak: Abbvie, Novartis, Roche, Janssen-Cilag: Consultancy. Kozak: Amgen, Novartis, Abbvie, Gilead Sciences: Consultancy; Abbvie, Tak: Other: Travel, Accommodations, Expenses. Šimkovič: Acerta Pharma: Consultancy; Gilead Sciences: Consultancy, Other: Travel, Accommodations, Expenses; Janssen-Cilag: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau; University Hospital Hradec Kralove: Current Employment; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Speakers Bureau. Kryachok: Takeda, Roche, Abbvie, MSD Oncology: Other: Travel, Accommodations, Expenses; Janssen Oncology, Bayer, Karyopharm Therapeutics, MSD Oncology, Acerta Pharma, Abbvie, Debiopharm Group: Research Funding; Takeda, Janssen Oncology: Consultancy. Illés: Takeda, Seattle Genetics: Research Funding; Novartis, Janssen, Pfizer, Roche;: Other: Travel, Accommodations, Expenses; Celgene, Janssen, Novartis,Roche, Takeda: Consultancy; Janssen, Celgene, Takeda, Novartis Pharma SAS, Pfizer Pharmaceuticals Israel, Roche;: Consultancy, Honoraria. de la Serna: Abbvie, Janssen: Speakers Bureau; Abbvie, AstraZeneca: Other: Travel, Accommodations, Expenses; Gilead, AstraZeneca, Abbvie, Janssen, Sandoz, F. Hoffmann-La Roche: Consultancy; Abbvie, Pharmacyclics, Novartis, Janssen, Acerta, AstraZeneca, BioGene, UCB, Sandoz: Honoraria; F. Hoffmann-La Roche, Abbvie, Pharmacyclics, Gilead, GlaxoSmithKline, Novartis, Janssen, Roche, Acerta, AstraZeneca, BioGene, UCB: Research Funding. Campbell: Amgen, Novartis, Roche, Janssen, Celgene (BMS): Research Funding; AstraZeneca, Janssen, Roche, Amgen, CSL Behring, Novartis: Consultancy. Musuraca: AstraZeneca, Debiopharm Group, Janssen, Gilead Sciences: Consultancy; TG Therapeutics, Acerta Pharma, AstraZeneca, Janssen, Bayer, Debiopharm Group, Epizyme, Merck, MorphoSys, MEI Pharma, Celerion, Roche, Servier, BeiGene: Research Funding. Jacob: AstraZeneca: Consultancy, Honoraria, Research Funding; AstraZeneca, GlaxoSmithKline, Horizon Discovery, Oxford Biomedica, Midlands Haematology Services: Current equity holder in publicly-traded company. Avery: AstraZeneca: Consultancy, Other: Travel, Accommodations, Expenses; Lilly: Research Funding. Wang: Acerta Pharma LLC: Current Employment; Global Blood Therapeutics.: Consultancy. Patel: AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Jurczak: Jagiellonian University: Ended employment in the past 24 months, Research Funding; Janssen, MeiPharma, Merck, Pharmacyclics, Roche, Tekeda, TG Therapeutics: Research Funding; Maria Sklodowska-Curie National Research Institute of Oncology: Consultancy, Current Employment.
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