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Objectives Ianalumab is an afucosylated, fully human IgG1 monoclonal antibody targeting B-cells through a novel dual mechanism of action of enhanced B-cell depletion through antibody-dependent cellular-cytotoxicity and inhibition of B-cell activation/survival via BAFF-R blockade. We expand upon previously published Phase 2 results of ianalumab in systemic lupus erythematosus (SLE) by adding post-end-of-treatment (EoT) data until end-of-study (EoS).Methods This multi-center, randomized, parallel-group Phase 2 study ( NCT03656562) enrolled patients with anti-nuclear antibodies >=1:80, 11 ACR 1997 SLE classification criteria >=4, SLEDAI-2K score >=6, BILAG-2004 >=1 A or >=2 B. Trial design: 28-week (W) blinded, placebo-controlled period; 24W open-label (OL) period to W52 (EoT); 16W post-treatment period to W68, followed by safety monitoring until EoS visit, triggered by patients achieving B-cell recovery (CD19+ B cell count >=50 cells/mcL or >=80% of baseline [BL]). Randomization was 1:1 subcutaneous ianalumab 300 mg or placebo every 4 weeks (q4w), with both arms switched at W28 to OL ianalumab through W48. Outcomes measured at BL, q4w to W52, W60, W68 and EoS included proportion patients achieving SRI-4 (component of composite primary endpoint), SRI-6, Lupus Low Disease Activity State (LLDAS), Definition of Remission in SLE (DORIS), safety/tolerability and laboratory markers of immune activation.Results Overall, 67 patients were enrolled and received >=one dose of ianalumab. BL characteristics were balanced across treatment groups. Median time to B-cell recovery post-EoT visit was 45W (range: 17W–187W). At W28, higher proportions of patients receiving ianalumab achieved SRI-4 (70.6%), SRI-6 (50.0%), LLDAS (17.6%), DORIS (11.8%), compared with placebo (30.3%, 21.2%, 9.1%, 3.0%, respectively). Further improvements observed with up to 1-year ianalumab treatment for most clinical and laboratory markers of disease activity persisted following EoT to B-cell recovery (EoS), with higher responder rates observed with longer ianalumab exposure (52W; 28W, respectively) for SRI-4 (58.8%; 39.4%), SRI-6 (44.1%; 30.3%), LLDAS (32.4%; 24.2%), DORIS (26.5%; 15.2%) ( figure 1, table 1). No unexpected/new safety signals or cases of new-onset neutropenia (CTCAE Grade 3/4) occurred during B-cell recovery.Abstract PO:11:275 Table 1Clinical and laboratory outcomes at Week 28, 52, 68 and EoSAbstract PO:11:275 Figure 1SRI-4 response over timeConclusions These data indicate patients may experience durable benefits following up to 1 year of ianalumab 300 mg monthly that persist during B-cell recovery. These data need further confirmation from pivotal trials.