Clinical Lymphoma, Myeloma & Leukemia, Vol.21, Suppl.1 - September 2021

Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2021 S318 CLL-115 First Results of a Head-to-Head Trial of Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia John C. Byrd 1 *, Peter Hillmen 2 , Paolo Ghia 3 , Arnon P. Kater 4 , Asher Chanan-Khan 5 , Richard R. Furman 6 , Susan O’Brien 7 , Mustafa Nuri Yenerel 8 , Arpad Illes 9 , Neil Kay 10 , Jose A. Garcia-Marco 11 , Anthony Mato 12 , Javier Pinilla-Ibarz 13 , John F. Seymour 14 , Stephane Lepretre 15 , Stephan Stilgenbauer 16 , Tadeusz Robak 17 , Priti Patel 18 , Kara Higgins 18 , Sophia Sohoni 18 , Wojciech Jurczak 19 1 The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA, 2 St. James’s University Hospital, Leeds, UK, 3 Università Vita-Salute San Raffaele and IRCCS Ospedale, San Raffaele, Milano, Italy, 4 Amsterdam University Medical Centers, Amsterdam, on behalf of Hovon, Netherlands, 5 Mayo Clinic Jacksonville, Jacksonville, FL, USA, 6 Weill Cornell Medicine, New York Presbyterian Hospital, New York, NY, USA, 7 Chao Family Comprehensive Cancer Center, University of California-Irvine, Irvine, CA, 8 Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey, 9 University of Debrecen, Debrecen, Hungary, 10 Mayo Clinic Rochester, Rochester, MN, USA, 11 Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain, 12 University of Pennsylvania, Philadelphia, PA, USA, 13 Moffitt Cancer Center, Tampa, FL, USA, 14 Peter MacCallum Cancer Centre & Royal Melbourne Hospital, Victoria, Australia, 15 Centre Henri Becquerel and Normandie University UNIROUEN, Rouen, France, 16 University of Ulm, Ulm, Germany, 17 Medican University of Lodz, Lodz, Poland, 18 AstraZeneca, South San Francisco, CA, USA, 19 Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland Co n text: Increased selectivity of the Bruton tyrosine kinase inhibitor (BTKi) acalabrutinib versus ibrutinib may improve tolerability. Objecti v e: To compare acalabrutinib versus ibrutinib in patients with chronic lymphocytic leukemia (CLL). D esig n : Open-label, randomized, noninferiority, phase 3 trial. Patie n ts: Previously treated CLL patients with del(1 7 p) or del(11q) by central lab. I n ter v e n tio n s: Oral acalabrutinib 100 mg twice daily (BID) or ibrutinib 420 mg once daily (QD) (stratified by del(1 7 p) status, Eastern Cooperative Oncology Group performance status [2 vs  1], and number of prior therapies [1–3 vs  4]) until progression or unacceptable toxicity. Mai n Outco m e Measures: Primary endpoint was progression-free survival (PFS), as assessed by independent review committee; secondary endpoints of all-grade atrial fibrillation (AF), grade  3 infection, Richter transformation, and overall survival (OS) were assessed in hierarchical order. Results: 533 patients (acalabrutinib, n=268; ibrutinib, n=265) were randomized (median age 66 years; median 2 prior therapies; del(1 7 p) 45.2%; del(11q) 64.2%). At a median follow-up of 40.9 months (range 0.0–59.1), acalabrutinib was noninferior to ibrutinib with a median PFS of 38.4 months in both arms (HR: 1.00; 95% CI: 0. 7 9–1.2 7 ). Acalabrutinib was statistically superior to ibrutinib in all-grade AF incidence (9.4% vs 16.0%; P=0.023). Among other secondary endpoints, incidences of grade  3 infection (acalabrutinib: 30.8%, ibrutinib: 30.0%) and Richter transformation (acalabrutinib: 3.8%, ibrutinib: 4.9%) were comparable between arms. Median OS was not reached in either arm (HR: 0.82; 95% CI: 0.59–1.15), with 63 (23.5%) deaths in the acalabrutinib arm and 7 3 (2 7 .5%) in the ibrutinib arm. Among any-grade adverse events (AEs) in  20% of patients in either arm, acalabrutinib was associated with lower incidence of hypertension (9.4%, 23.2%), arthralgia (15.8%, 22.8%), and diarrhea (34.6%, 46.0%) but a higher incidence of headache (34.6%, 20.2%) and cough (28.9%, 21.3%). AEs led to treatment discontinuation in 14. 7 % of acalabrutinib- versus 21.3% of ibrutinib-treated patients. Any-grade AEs of clinical interest that were less frequent with acalabrutinib included cardiac (24.1% vs 30.0%), hypertension (above), and bleeding events (38.0% vs 51.3%). Co n clusio n s: In this first head-to-head trial of BTKis in CLL, acalabrutinib demonstrated noninferior PFS with less cardiotoxicity and fewer discontinuations due to AEs versus ibrutinib. Keywords: CLL, acalabrutinib, ibrutinib, chronic lymphocytic leukemia, Bruton tyrosine kinase CLL-139 Acalabrutinib ± Obinutuzumab vs Obinutuzumab + Chlorambucil in Treatment-Naïve Chronic Lymphocytic Leukemia: ELEVATE-TN 4-Year Follow- up Jeff P. Sharman 1 *, Miklos Egyed 2 , Wojciech Jurczak 3 , Alan Skarbnik 4 , John M. Pagel 5 , Ian W. Flinn 6 , Manali Kamdar 7 , Talha Munir 8 , Renata Walewska 9 , Gillian Corbett 10 , Laura Maria Fogliatto 11 , Yair Herishanu 12 , Versha Banerji 13 , Steven Coutre 14 , George Follows 15 , Patricia Walker 16 , Karin Karlsson 17 , Paolo Ghia 18 , Ann Janssens 19 , Florence Cymbalista 20 , Jennifer A. Woyach 21 , Emmanuelle Ferrant 22 , William G. Wierda 23 , Veerendra Munugalavadla 24 , Priti Patel 24 , Min Hui Wang 24 , John C. Byrd 21 1 Willamette Valley Cancer Institute and Research Center, Eugene, Oregon, United States, 2 Somogy County Mór Kaposi General Hospital, Kaposvár, Hungary, 3 Maria Skłodowska-Curie National Research Institute of Oncology, Krakow, Poland, 4 Novant Health Cancer Institute, Charlotte, North Carolina, United States, 5 Swedish Cancer Institute, Center for Blood Disorders and Stem Cell Transplantation, Seattle, Washington, United States, 6 Sarah Cannon Research Institute, Tennessee Oncology Nashville, Nashville, TN, USA, 7 University of Colorado Cancer Center, Aurora, Colorado, United States, 8 Haematology, Haematological Malignancy Diagnostic Service (HMDS), St. James’s Institute of Oncology, Leeds, United Kingdom, 9 Cancer Care, University Hospitals Dorset, Bournemouth, United Kingdom, 10 Tauranga Hospital, Tauranga, New Zealand, 11 Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil, 12 Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, 13 Departments of Internal Medicine, Biochemistry & Medical Genetics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba and CancerCare