We report follow-up results from the randomized, placebo-controlled, phase 3 HELIOS trial of ibrutinib+bendamustine and rituximab (BR) for previously treated chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) without deletion 17p. Overall, 578 patients were randomized 1:1 to either ibrutinib (420 mg daily) or placebo, in combination with 6 cycles of BR, followed by ibrutinib or placebo alone. Median follow-up was 34.8 months (range: 0.1-45.8). Investigator-assessed median progression-free survival (PFS) was not reached for ibrutinib+BR, versus 14.3 months for placebo+BR (hazard ratio [HR] [95% CI], 0.206 [0.159-0.265]; P < 0.0001); 36-month PFS rates were 68.0% versus 13.9%, respectively. The results are consistent with the primary analysis findings (HR = 0.203, as assessed by independent review committee, with 17-month median follow-up). Median overall survival was not reached in either arm; HR (95% CI) for ibrutinib+BR versus placebo: 0.652 (0.454-0.935; P = 0.019). Minimal residual disease (MRD)-negative response rates were 26.3% for ibrutinib+BR and 6.2% for placebo+BR (P < 0.0001). Incidence of treatment-emergent adverse events (including grades 3-4) were generally consistent with the initial HELIOS report. These long-term data support improved survival outcomes and deepening responses with ibrutinib+BR compared with BR in relapsed CLL/SLL.

1st Department of Propedeutic Medicine National and Kapodistrian University of Athens Athens Greece

Department 1 of Internal Medicine University of Cologne Cologne Germany

Department of Cancer Prevention Faculty of Public Health Silesian Medical University Katowice Poland

Department of Haematology Plymouth University Medical School Plymouth UK

Department of Hematology Cherkassy Regional Oncological Center Cherkassy Ukraine

Department of Hematology Fundaleu Buenos Aires Argentina

Department of Hematology Karolinska University Hospital Stockholm Sweden

Department of Internal Medicine Center of Integrated Oncology and German CLL Study Group University of Cologne Cologne Germany

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

Department of Oncology Pathology Karolinska Institutet Stockholm Sweden

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 Medical Oncology British Columbia Cancer Agency Vancouver BC Canada

Hematology Department Hospital Universitario La Princesa IIS IP Madrid Spain

Hôpital Haut Lévêque Pessac Bordeaux France

IEP São Lucas Hemomed Oncologia e Hematologia São Paulo Brazil

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 at Hackensack University Medical Center Hackensack NJ USA

Juravinski Cancer Centre McMaster University Hamilton ON Canada

Mayo Clinic Cancer Center Jacksonville FL USA

Nizhny Novogorod Regional Clinical Hospital Nizhny Novogorod Russia

Regional Clinical Hospital Ryazan Russia

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

Universitaire Ziekenhuizen Leuven Leuven Belgium

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