Acalabrutinib vs Idelalisib plus Rituximab (IdR) or Bendamustine plus Rituximab (BR) in Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): ASCEND Final Results

November 2020 Vol 11, No 11
Paolo Ghia, MD
Università Vita-Salute San Raffaele and IRCCS Ospedale San Raffaele,
Milano, Italy
Andrzej Pluta, MD
Department of Hematological Oncology, Oncology Specialist Hospital,
Brzozow, Poland
Malgorzata Wach, MD
Department of Hemato-Oncology and Bone Marrow Transplantation, Medical University of Lublin,
Lublin, Poland
Daniel Lysak, MD
Fakultní Nemocnice Plzeň,
Pilsen, Czech Republic
Tomas Kozak, MD
Fakultní Nemocnice Královske Vinohrady,
Prague, Czech Republic
Martin Simkovic, MD
University Hospital Hradec Kralove, Charles University,
Hradec Kralove, Czech Republic
Polina Kaplan, MD
Dnipropetrovsk City Clinical Hospital No. 4,
Dnipropetrovsk, Ukraine
Iryna Kraychok, MD
National Cancer Institute,
Kiev, Ukraine
Arpad Illes, MD
University of Debrecen, Faculty of Medicine, Department of Hematology, Hungary
Javier de la Serna, MD
Hospital Universitario 12 de Octubre,
Madrid, Spain
Sean Dolan, MD
Saint John Regional Hospital, University of New Brunswick,
New Brunswick, Canada
Philip Campbell, MD
Barwon Health, University Hospital Geelong,
Geelosng, Victoria, Australia
Gerardo Musuraca, MD
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori,
Meldola, Italy
Abraham Jacob, MD
The Royal Wolverhampton NHS Trust,
Wolverhampton, United Kingdom
Eric J. Avery, MD
Nebraska Hematology Oncology,
Lincoln, NE
Jae Hoon Lee, MD
Gachon University Gil Medical Center,
Incheon, South Korea
Denise Wang
Acerta Pharma, South San Francisco, CA, USA
Priti Patel, MD
Acerta Pharma,
South San Francisco, CA, USA
Wojciech Jurczak, MD
Department of Hematology, Jagiellonian University Medical College,
Krakow, Poland

Background: Acalabrutinib is a next-generation, highly selective, covalent Bruton tyrosine kinase inhibitor approved for patients with CLL, including those with R/R CLL.

Objectives: The efficacy and safety of acalabrutinib alone versus IdR or BR were shown in patients with R/R CLL in a preplanned interim analysis of ASCEND; final results are reported herein.

Methods: In this randomized, multicenter, phase 3, open-label study (NCT02970318), patients with R/R CLL were randomized 1:1 to receive oral (PO) acalabrutinib 100 mg twice daily (bid) or investigator’s choice of IdR (Id: 150 mg PO bid until progression or toxicity; R: 375 mg/m2 × 1, then 500 mg/m2 IV for 8 total infusions) or BR (B: 70 mg/m2 IV and R: 375 mg/m2 × 1, 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. All patients provided informed consent.

Results: A total of 310 patients (acalabrutinib, n = 155; IdR, n = 119; BR, n = 36) were enrolled (median age: 67 years; del[17p] 16%, del[11q] 27%, Rai stage 3/4 42%). At a median follow-up of 22.0 months, acalabrutinib significantly prolonged investigator-assessed PFS versus IdR/BR (median: not reached vs 16.8 months; hazard ratio: 0.27; P <.0001); 18-month PFS rates were 82% for acalabrutinib and 48% for IdR/BR. The 18-month OS rate was 88% for both treatment regimens. The ORR was 80% with acalabrutinib versus 84% with IdR/BR; ORR including partial response with lymphocytosis was 92% versus 88%, respectively. The most common adverse events (AEs; any grade [grade ≥3]) by treatment group were: acalabrutinib, headache (22% [1%]), neutropenia (21% [17%]), and diarrhea (20% [2%]); IdR, diarrhea (49% [25%]) and neutropenia (46% [40%]); BR, neutropenia (34% [31%]), fatigue (23% [3%]), infusion-related reaction (23% [3%]), and nausea (20% [0%]). AEs led to drug discontinuation in 16% of acalabrutinib, 56% of IdR, and 17% of BR patients. AEs of interest included atrial fibrillation (acalabrutinib 6%, IdR/BR 3%), major hemorrhage (all grade; acalabrutinib 3%, IdR/BR 3%), grade ≥3 infections (acalabrutinib 20%, IdR/BR 25%), and second primary malignancies excluding nonmelanoma skin cancer (acalabrutinib 5%, IdR/BR 2%).

Conclusions: Final ASCEND results with additional follow-up confirm earlier findings and support the favorable efficacy and safety of acalabrutinib compared with standard-of-care regimens in patients with R/R CLL.

Support: This study was sponsored by Acerta Pharma, a member of the AstraZeneca group.

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