P020 Infusion-related reactions and haematological events associated with obinutuzumab in lupus nephritis: a secondary analysis of the REGENCY trial

Abstract Background/Aims The REGENCY (NCT04221477) trial demonstrated superior efficacy of obinutuzumab and standard therapy (OBI+ST) over placebo and ST (PBO+ST) in patients with active lupus nephritis (LN). Insights related to infusion-related reactions (IRRs) and haematological effects of obinutuzumab could guide management of LN. This study characterised the IRR profile and occurrence of neutropenia in the REGENCY trial. Methods Incidence, severity and attribution of IRRs and haematological abnormalities, including drug-related neutropenia, were determined based on investigator and NCI CTCAE v5.0 adverse event grading. Results The proportion of patients who experienced at least one IRR was higher in the OBI+ST vs the PBO+ST arm (21 15.4% vs 15 11.4%). In the OBI+ST arm, the majority (19 14.0%) experienced IRRs of Grade 1-2, which resolved. In the OBI+ST arm, 2 patients (1.5%) experienced Grade 3-4 IRRs; both events resolved. The most frequently reported symptoms of IRRs in the obinutuzumab vs placebo arms respectively were nausea (4 2.9% vs 4 3.0%), headache (4 2.9% vs 3 2.3%) and vomiting (4 2.9% vs 2 1.5%). IRR incidence and severity was highest at first infusion, with Grade 3-4 observed only then (Table 1). The proportion of patients who experienced at least one drug-related neutropenia was higher in the OBI+ST arm vs the PBO+ST arm (17 12.5% vs 5 3.8%). Most cases of neutropenia were detected during routine haematology labs at scheduled study visits. Median time for resolution was 16 days (min-max: 4-378 days) and 50.5 days (min-max: 21-371 days) in the OBI+ST and PBO+ST arm, respectively. Seven patients (4.1%) had Grade 3-4 drug-related neutropenia (including 1 febrile neutropenia), none occurred in the PBO+ST arm. All drug-related neutropenia resolved with treatment except for one placebo patient where it was resolving at clinical cutoff. No Grade 5 neutropenia was observed. Five patients received G-CSF treatment for drug-related neutropenia (4 in the OBI+ST arm vs 1 in the PBO+ST arm). Conclusion The incidence of IRRs and drug-related neutropenia was higher in patients receiving OBI+ST but risks remained low overall; many were Grade 1-2, self-limited, easily manageable and without consequence. These data provide insights into obinutuzumab-related adverse events. Disclosure R.A. Furie: Other; R.F. has received research support and consulting fees from Chugai Pharmaceutical Co., Ltd., F. Hoffmann-La Roche Ltd, Genentech, Inc. and GlaxoSmithKline. T. Baczkowska: None. A. Saxena: Other; A.S. has received research support and/or consulting fees from AbbVie, Amgen, AstraZeneca, Aurinia, Bristol Myers Squibb, GlaxoSmithKline, Synthekine and UCB. I. Hassan: Other; I.H. is an employee of F. Hoffmann-La Roche Ltd. B. Yoo: Other; B.Y. is employee of Genentech, Inc. and shareholder of F. Hoffmann-La Roche Ltd. B. Lanza: Other; B.L. is an employee of employee and shareholder of F. Hoffmann-La Roche Ltd. H. Sehgal: Other; H.S. is an employee and shareholder of F. Hoffmann-La Roche Ltd. F. Boissard: Other; is an employee of F. Hoffmann-La Roche Ltd. J.P. Garg: Other; J.P.G. is an employee of Genentech, Inc. and shareholder of F. Hoffmann-La Roche Ltd. T. Schindler: Other; T.S. is an employee and shareholder of F. Hoffmann-La Roche Ltd. E. Martins: Other; E.M. is an employee and shareholder of F. Hoffmann-La Roche Ltd. W.F. Pendergraft: Other; W.F.P. is an employee of Genentech, Inc. and shareholder of F. Hoffmann-La Roche Ltd. B. Rovin: Other; B.H.R. has received consulting fees from F. Hoffmann-La Roche Ltd/Genentech, Inc.