GADOLIN: Primary results from a phase III study of obinutuzumab plus bendamustine compared with bendamustine alone in patients with rituximab-refractory indolent non-Hodgkin lymphoma.

Lymphoma and Plasma Cell Disorders
Session Type and Session Title: 
Oral Abstract Session, Lymphoma
Abstract Number: 


J Clin Oncol 33, 2015 (suppl; abstr LBA8502)
Laurie Helen Sehn, Neil Sun Chua, Jiri Mayer, Gregory Scott Dueck, Marek Trněný, Kamal Bouabdallah, Nathan Hale Fowler, Vincent Delwail, Oliver W. Press, Gilles A. Salles, John G. Gribben, Anne Lennard, Pieternella J. Lugtenburg, Natalie Franklin, Elisabeth Wassner Fritsch, Guenter Fingerle-Rowson, Bruce D. Cheson; BC Cancer Agency, Vancouver, BC, Canada; Department of Oncology, Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada; Hematology and Oncology, University Hospital Brno and Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Medical Oncology, BC Cancer Agency, Kelowna, BC, Canada; First Faculty of Medicine, Charles University General Hospital, Prague, Czech Republic; Department of Haematology, CHU Haut-Lévèque, Pessac, France; The University of Texas MD Anderson Cancer Center, Houston, TX; Department of Oncology-Hematology and Cell Therapy, University Hospital, Poitiers, France; Fred Hutchinson Cancer Research Center, Seattle, WA; Hospices Civils de Lyon, Université Claude Bernard, Pierre Bénite, France; Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University of London, London, United Kingdom; Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, United Kingdom; Department of Hematology, Erasmus MC Cancer Insitute, Rotterdam, Netherlands; Biostatistics, F. Hoffmann-La Roche, Welwyn Garden City, United Kingdom; Pharma Development Oncology, F. Hoffmann-La Roche, Basel, Switzerland; Georgetown University Hospital, Washington, DC

Abstract Disclosures


Background: Treatments are limited and outcomes poor in rituximab-refractory (Rit-Ref) iNHL. Bendamustine (B) has a 9 mo median PFS and 10 mo response duration in ph II trials. Obinutuzumab (GA101/Gazyva [G]) is a glycoengineered type II aCD20 mAb with activity and acceptable safety in Rit-Ref NHL. Methods: GADOLIN (NCT01059630) is a ph III open label study in pts with CD20+ Rit-Ref iNHL. In the B arm, pts received B 120 mg/m2 (d1+2, c1–6) alone; GB arm pts received B 90 mg/m2 (d1+2, c1–6) with G 1000 mg (d1, 8, 15 c1, d1 c2–6) for up to six 28d cycles. Non-PD GB pts then received G monotherapy every 2 mo for up to 2 yrs. Primary endpoint was PFS assessed by an independent radiology facility (IRF), with 80% power to detect 43% improvement in median PFS. Results: In the protocol specified interim analysis, 396 pts were randomized to receive B (n = 202 [198 treated]) or GB (n = 194). The IDMC recommended to unblind the study as the primary endpoint had been reached (4 Feb 2015). Baseline characteristics were balanced between arms. Median age was 63 yrs and pts had a median of 2 prior therapies. Median observation time was 20 mo (B) and 22 mo (GB). IRF-assessed median PFS was 14.9 mo (B) and not reached (NR) for GB (HR 0.55, 95% CI 0.4–0.74; p = 0.00011). Median investigator-assessed PFS was 14 mo for B and 29 mo for GB (HR 0.52, 95% CI 0.39–0.70; p < 0.0001). There were no significant differences in IRF-assessed ORR (63.0% B vs 69.1% GB) or CR (12.2% B vs 11.2% GB) at end of induction, in IRF-assessed best overall response up to 12 mo from start of treatment (76.6% B vs 78.6% GB), or in preliminary OS (median OS NR in either arm). In the treatment period, there were fewer Grade ≥ 3 adverse events with B than GB (62.1% B vs 68% GB), notably neutropenia (26.3% B vs 33.0% GB) and infusion-related reactions (3.5% B vs 8.8% GB), but more Grade ≥ 3 thrombocytopenia (16.2% B vs 10.8% GB), anemia (10.1% B vs 7.7% GB) and pneumonia (5.6% B vs 2.6% GB). Conclusions: G combined with B (90 mg/m2) followed by G maintenance significantly improved PFS vs B alone (120 mg/m2) in Rit-Ref iNHL. The clinically meaningful PFS improvement with GB is the first randomized evidence of benefit for a novel aCD20 mAb in Rit-Ref iNHL. Clinical trial information: NCT01059630