Obinutuzumab (GA101) plus chlorambucil (Clb) or rituximab (R) plus Clb versus Clb alone in patients with chronic lymphocytic leukemia (CLL) and preexisting medical conditions (comorbidities): Final stage 1 results of the CLL11 (BO21004) phase III trial.

Leukemia Myelodysplasia and Transplantation
Session Type and Session Title: 
Oral Abstract Session, Leukemia, Myelodysplasia, and Transplantation
Abstract Number: 
J Clin Oncol 31, 2013 (suppl; abstr 7004)
Valentin Goede, Kirsten Fischer, Kathryn Humphrey, Elina Asikanius, Raymonde Busch, Anja Engelke, Clemens M. Wendtner, Olga Samoylova, Tatiana Chagorova, Marie-Sarah Dilhuydy, Javier De La Serna Torroba, Thomas Illmer, Stephen Opat, Carolyn Owen, Karl A Kreuzer, Anton W Langerak, Matthias Ritgen, Stephan Stilgenbauer, Michael Wenger, Michael Hallek; German CLL Study Group, Dept. I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, Cologne, Germany; Department I of Internal Medicine and Center of Integrated Oncology Cologne Bonn, University of Cologne, Cologne, Germany; F. Hoffmann-La Roche Ltd, Welwyn, England; F. Hoffmann-La Roche Ltd, Basel, Switzerland; Institute of Medical Statistics and Epidemiology, Technical University Munich, Munich, Germany; Department of Hematology and Oncology, Schwabing Hospital Munich, Munich, Germany; Hematology, Regional Clinical Hospital N.A. Semashko, Nizhny Novgorod, Russia; Penza Regional Oncology Dispensary, Penza, Russia; Hopital De Haut Leveque, Hematologie Clinique, Pessac, France; Hospital Univ 12 De Octubre, Servicio De Hematologia, Madrid, Spain; Private Oncology Practice, Dresden, Germany; Monash Medical Centre, Haematology, Clayton, Australia; Tom Baker Cancer Centre, Calgary, AB, Canada; Deptartment I of Internal Medicine, Center of Integrated Oncology Cologne-Bonn, University Hospital Cologne, Cologne, Germany; Department of Immunology, Erasmus Medical Center Rotterdam, Rotterdam, Netherlands; Medical Department II, University of Schleswig Holstein, City Hospital Kiel, Kiel, Germany; Department of Internal Medicine III, University of Ulm, Ulm, Germany

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Chemoimmunotherapy (CIT) is standard of care in young and physically fit patients (pts) with CLL. Development of CIT for older and less fit CLL pts is ongoing, but data from phase III trials are sparse. CLL11 is the largest trial to evaluate three treatments in previously untreated CLL pts with comorbidities: Clb alone, GA101 + Clb (GClb), R + Clb (RClb). The final analysis of CLL11 stage 1 efficacy and safety results is presented here. Methods: Treatment-naïve CLL pts with a Cumulative Illness Rating Scale (CIRS) total score >6 and/or an estimated creatinine clearance (CrCl) <70 mL/min were eligible. Pts received Clb alone (0.5 mg/kg po d1, d15 q28 days, 6 cycles), GClb (100 mg iv d1, 900 mg d2, 1000 mg d8, d15 of cycle 1, 1000 mg d1 cycles 2-6), or RClb (375 mg/m2 iv d1 cycle 1, 500 mg/m2 d1 cycles 2-6). Primary endpoint was investigator-assessed progression-free survival (PFS). Results: Median age, CIRS score, and CrCl at baseline were 73 years, 8, and 61.1 mL/min for stage 1a (Clb vs GClb, 356 pts) and 73 years, 8, and 62.1 mL/min for stage 1b (Clb vs RClb, 351 pts, triggered by a different event rate). Key efficacy and safety results are shown in the Table.Grade 3-4 infusion-related reactions with GClb occurred at first infusion only. Management required splitting the first dose over 2 days. Conclusions: CIT with GClb or RClb significantly prolongs PFS vs Clb alone. The results demonstrate that GClb and RClb are very active in CLL and superior treament options in this population. GClb vs RClb will be compared in stage 2 analysis with more follow-up available. Clinical trial information: NCT01010061.

Total stage 1
Stage 1a
Stage 1b
Median observation time, months 13.6 14.5 14.2 15.3
Overall response rate, % 30.2 75.5 30.0 65.9
Complete responses, % 0 22.2 0 8.3
Median PFS, months 10.9 23.0* 10.8 15.7
HR, CI, p 0.14, 0.09-0.21, <.0001 0.32, 0.24-0.44, <.0001
Grade 3-5 adverse events
during treatment, %
41 67 41 46
Infusion-related reaction - 21 - 4
Neutropenia 15 34 15 25
Infections 11 6 11 8

* Still immature, < 20% at risk at time of median.