Background: The efficacy of copanlisib, an intravenous pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor, was demonstrated in the Phase II CHRONOS-1 study in patients with relapsed or refractory indolent B-cell lymphoma (Dreyling et al. J Clin Oncol 2017). Copanlisib was approved by the US Food and Drug Administration in 2017 for the treatment of patients with follicular lymphoma (FL) who have received ≥2 therapies. Here, we describe updated efficacy and safety data from patients with FL at the 6-year follow-up of CHRONOS-1. Methods: CHRONOS-1 included patients with relapsed or refractory indolent FL (grades 1-3a) who had received ≥2 lines of therapy. Copanlisib 60 mg was administered via intravenous infusion on days 1, 8, and 15 of a 28-day cycle. Objective tumor response rate (ORR) was assessed by independent radiologic review (Cheson et al. J Clin Oncol 2007) as the primary efficacy endpoint. Safety analysis included adverse events graded using CTCAE v4.03. Results: 104 patients with FL were treated in CHRONOS-1, of whom 99.0% (n= 103) discontinued treatment at the time of database cut-off on June 30, 2022. 72% of patients (n= 75) received ≥1 line of subsequent systemic anti-cancer therapy during follow-up, with 40% receiving a rituximab-based regimen. At the cut-off, ORR (primary endpoint) was 57.7% (n= 60), with 19.2% (n= 20) of patients achieving a complete response. Median duration of response was 12.2 months (range 1.1-48.1). Median progression-free survival (PFS) was 11.2 months (range 0.2-51.5) with a median follow-up of 20.7 months (95% confidence interval [CI] 11.5, 31.5); PFS rate was 32% at 2 years. Median overall survival was 46.3 months (range 0.7-82.9) with a total of 56 events and a median follow-up of 82.4 months (95% CI 79.3, 84.9); survival rate was 43% at 6 years. Median duration of treatment was 6.0 months (range 0.23-80.9). No patients experienced transformation to aggressive lymphoma (diffuse large B-cell lymphoma). The primary reasons for stopping treatment included radiologic disease progression (42.3%; n= 44) and adverse events not associated with clinical disease progression (29.8%; n= 31). The safety profile was consistent with the reported 2-year follow-up data (Dreyling et al. Am J Hematol 2020). The most common treatment-emergent adverse events (all grades/grades 3-4) were infusion-related hyperglycemia (50.0%/39.5%), diarrhea (36.5%/8.7%), hypertension (28.8%/23.1%), pyrexia (27.9%/4.8%), and neutropenia (26.0%/23.0%). Conclusions: Copanlisib continued to induce robust response and durable survival in patients with relapsed or refractory indolent FL at 6 years of follow-up. Copanlisib was well tolerated, with no new safety signals and no evidence of malignant transformation. These results further support the long-term use of copanlisib in this patient population. Clinical trial information: NCT01660451.