Infusion-Related Reactions (IRRs) and Hematologic Events Associated with Obinutuzumab in Lupus Nephritis: A Secondary Analysis of a Phase III Trial

Objectives The REGENCY (NCT04221477) trial demonstrated superior efficacy of obinutuzumab and standard therapy (OBI+ST) over placebo and ST (PBO+ST) in patients (pts) with active lupus nephritis (LN). Insights related to IRRs and hematologic effects of OBI would help guide future management of LN. This study characterized the IRR profile and occurrence of neutropenia in the REGENCY trial.

Methods Incidence, severity and attribution of IRRs and hematologic abnormalities, including drug-related neutropenia, were determined based on investigator and NCI CTCAE v5.0 adverse event grading.

Results The proportion of pts who experienced at least 1 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 (Gr) 1-2, which resolved. In the OBI+ST arm, 2 pts (1.5%) experienced Gr 3-4 IRRs; both events resolved. No Gr 5 IRRs were observed. The most frequently reported symptoms of IRRs in the OBI vs PBO 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 Gr 3-4 observed only then (Table 1). The shifts observed from Gr 1-2 at baseline to Gr 3-4 post-baseline were notably different between the treatment arms for neutrophils and lymphocytes. As lymphopenia is an expected pharmacologic effect of anti-CD20 therapies, this analysis focused on drug-related neutropenia. The proportion of pts who experienced at least 1 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 incidentally detected during routine hematology labs at scheduled study visits. Median time for resolution was 16 days (d) (min-max: 4-378 d) and 50.5 d (min-max: 21-371 d) in the OBI+ST and PBO+ST arm, respectively. Seven pts (4.1%) had Gr 3-4 drug-related neutropenia (including 1 febrile neutropenia), while none occurred in the PBO+ST arm. All drug-related neutropenia resolved with treatment except for 1 PBO pt where it was resolving at clinical cutoff. No Gr 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 pts receiving OBI+ST but risks remained low overall; many were Gr 1-2, self-limited, easily manageable and without consequence. These data provide insights into adverse events related to OBI.