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.

LBA8502 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.

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