Obinutuzumab plus CHOP is effective and has a tolerable safety profile in previously untreated, advanced diffuse large B-cell lymphoma: the phase II GATHER study

Abstract

This study investigated the safety and efficacy of obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (G-CHOP) in patients with advanced diffuse large B-cell lymphoma (DLBCL) and explored the impact of cell-of-origin (COO) on patient outcomes. Patients (N = 100) received obinutuzumab (1000 mg on the days 1, 8, and 15 of cycle 1, and day 1 of cycles 2-8) plus CHOP (cycles 1-6). For patients without grade ≥3 infusion-related reactions (IRRs) to standard-rate obinutuzumab infusion, a shorter duration of infusion (SDI) was evaluated. Overall and complete response rates, as determined according to the Cheson et al. criteria by investigators/independent radiological facility, were 82.0/75.0% and 55.0/58.0%, respectively. SDI of 120 minutes and 90 minutes were well tolerated with no grade ≥3 IRRs. Among all patients, IRRs typically occurred during cycle 1, day 1. G-CHOP is active and has an acceptable safety profile in the first-line treatment of patients with advanced DLBCL. Clinical Trials: NCT01414855DLBCL.

Keywords: Efficacy; obinutuzumab; safety profile.

Figure 1.

Patient disposition. *Planned treatment consisted of obinutuzumab administered as 1000 mg IV on day 1 of a 21-day cycle for 8 cycles, with additional doses on days 8 and 15 of cycle 1. ^†One additional patient completed the study and then died due to a secondary malignancy. AE: adverse event; IV: intravenous; PD: progressive disease.

Figure 2.

Progression-free survival. (A) Investigator-assessed PFS of all patients in the study after a median observation time of 50.7 months. Median PFS was 48.3 months. (B) PFS according to IPI: low risk/low-intermediate risk (0–2) versus high risk/high-intermediate risk (3–5). (C) PFS according the COO as determined by a modification of the Wright et al.^[25] DLBCL gene expression classifier (see Methods). COO could be assigned in 78 cases: 45 GCB, 19 ABC. ABC: activated B-cell; COO: cell-of-origin; DLBCL: diffuse large B-cell lymphoma; GCB: germinal center B-cell; IPI: International Prognostic Index; PFS: progression-free survival.