We report final analysis outcomes from the phase 3 HELIOS study (NCT01611090). Patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma without deletion 17p (n = 578) were randomized 1:1 to 420 mg daily ibrutinib or placebo plus ≤6 cycles of bendamustine plus rituximab (BR), followed by ibrutinib or placebo alone. Median follow-up was 63.7 months. Median investigator-assessed progression-free survival was longer with ibrutinib plus BR (65.1 months) than placebo plus BR (14.3 months; hazard ratio [HR] 0.229 [95% confidence interval (CI) 0.183-0.286]; p < .0001). Despite crossover of 63.3% of patients from the placebo plus BR arm to ibrutinib treatment upon disease progression, ibrutinib plus BR versus placebo plus BR demonstrated an overall survival benefit (HR 0.611 [95% CI 0.455-0.822]; p = .0010; median not reached in either arm). Long-term follow-up data confirm the survival benefit of ibrutinib plus BR over BR alone. Safety profiles were consistent with those known for ibrutinib and BR.

Department 1 of Internal Medicine and German CLL Study Group University of Cologne Faculty of Medicine and University Hospital of Cologne Cologne Germany

Department of Haematology University of Plymouth Medical School Plymouth UK

Department of Hematology and Cancer Prevention School of Public Health Silesian Medical University Katowice Poland

Department of Hematology Fundaleu Buenos Aires Argentina

Department of Internal Medicine Hematology and Oncology University Hospital Brno Jihlavska Brno Czech Republic

Division of Hematology and Bone Marrow Transplantation Chaim Sheba Medical Center Tel Hashomer and Sackler School of Medicine University of Tel Aviv Tel Aviv Israel

Division of Hematology Dokuz Eylul University Izmir Turkey

Division of Hematology Mayo Clinic Cancer Center Jacksonville FL USA

Hematology Department Hospital Universitario La Princesa IIS IP Madrid Spain

Hopital Haut Leveque Bordeaux France

IEP São Lucas Hemomed Oncologia e Hematologia São Paulo Brazil

Janssen Cilag Neuss Germany

Janssen Research and Development High Wycombe UK

Janssen Research and Development Raritan NJ USA

Janssen Research and Development Spring House PA USA

John Theurer Cancer Center Hackensack University Medical Center Hackensack NJ USA

Juravinski Cancer Centre McMaster University Hamilton Canada

Memorial Sloan Kettering Cancer Center NY USA

Nizhny Novogorod Regional Clinical Hospital Nizhny Novogorod Russia

Siteman Cancer Center Washington University School of Medicine St Louis MO USA

Universitaire Ziekenhuizen Leuven Leuven Belgium

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NCT01611090