Copanlisib, an intravenous pan-class I phosphatidylinositol 3-kinase (PI3K) inhibitor, appears to induce robust responses and durable survival in patients with relapsed or refractory indolent follicular lymphoma (FL) at 6 years of follow-up, according to new data presented at the ASCO Annual Meeting 2023. Additionally, the longer follow-up turned up no new safety signals and no evidence of malignant transformation.

The phase 2 CHRONOS-1 study confirmed that copanlisib was effective and it was subsequently approved by the US Food and Drug Administration in 2017 for the treatment of patients with follicular lymphoma (FL) who already had received ≥2 therapies ( Identifier: NCT01660451).

“The long-term overall survival in relapsed FL is quite surprising and in contrast to other studies. These remarkable results of such a median sized study are definitely supporting the application of the PI3K inhibitor in the therapeutic algorithm of follicular lymphoma,” said Martin H. Dreyling of LMU University Hospital, Munich, Germany, when commenting on the study results in an email interview.

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All the patients had relapsed or refractory indolent FL (grades 1-3a) and had received ≥2 lines of therapy. Copanlisib (60 mg via intravenous infusion on days 1, 8, and 15 of a 28-day cycle) was assessed by objective tumor response rate (ORR) assessed by independent radiologic review as the primary efficacy endpoint.

The study included 104 patients and 99.0% (n=103) had already discontinued treatment at the time of database cut-off on June 30, 2022. During the follow-up period, 72% of patients (n=75) had received ≥1 line of subsequent systemic anti-cancer therapy, with 40% receiving a rituximab-based regimen.

At the time of the database cut-off, the ORR was 57.7% (n=60), with 19.2% (n=20) of patients achieving a complete response (CR). With a median follow-up of 20.7 months, the median duration of response was 12.2 months (range, 1.1-48.1) and the median progression-free survival (PFS) was 11.2 months (range, 0.2-51.5). The median PFS rate was 32% at 2 years.

Survival rates indicated a median overall survival (OS) of 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). At 6-years, the survival rate was 43% and the median duration of treatment was 6.0 months (range, 0.23-80.9). There researchers found that none of the patients experienced transformation to aggressive lymphoma (diffuse large B-cell lymphoma).

Radiologic disease progression (42.3%; n=44) was the primary reason for stopping treatment and other adverse events (AEs) not associated with clinical disease progression (29.8%; n=31). Further, no new safety problems were found and the safety profile was consistent with the reported 2-year follow-up data. With 6 years of follow-up, the most common treatment-emergent adverse events included infusion-related hyperglycemia (50.0% all grade; 39.5% grade 3-4), diarrhea (36.5% all grade; 8.7% grade 3-4), hypertension (28.8% all grade; 23.1% grade 3-4), pyrexia (27.9% all grade; 4.8% grade 3-4), and neutropenia (26.0% all grade; 23.0% grade 3-4).

“From my point of view, the most important aspect of taking care of patients with relapsed follicular lymphoma is to consider the long-term outcome of the disease after a sequence of multiple salvage treatments. Therefore, the results of the long-term follow-up of CHRONOS-1 have quite some significant relevance for clinical care of these patients,” said Dr Dreyling.


Dreyling MH, Santoro A, Leppä S, et al. Six-year safety and efficacy results from the CHRONOS-1 study of the PI3K inhibitor copanlisib in patients with relapsed or refractory follicular lymphoma. ASCO 2023. June 2-6, 2023. Abstract 7555.