Copanlisib appears to be safe and effective for treating relapsed or refractory indolent B cell lymphoma, according to a long-term analysis of the CHRONOS-1 trial published in the American Journal of Hematology.1

Relapse and refractory disease are common in indolent B cell lymphomas, contributing to a high rate of mortality. While some phosphatidylinositol 3-kinase (PI3K) inhibitors have shown promise in this setting, a high rate of toxicity has led to black box warnings by the US Food and Drug Administration (FDA).

Despite noted toxicities, the FDA approved copanlisib, an intravenous pan-class PI3K inhibitor, for third-line treatment in indolent B cell lymphomas, largely based on the results of the phase 2 CHRONOS-1 study. Initial results from CHRONOS-1 showed an objective response rate of 59.2% in the 142 included patients, and a median safety follow-up of 24 weeks showed a low adverse event (AE) rate. The FDA’s approval of copanlisib in this setting was, furthermore, given without the aforementioned black box warning.

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For the present paper, researchers conducted a 2-year safety and efficacy follow-up analysis to determine whether long-term data support the initial toxicity findings.

The frequency of grade 3 to 4 treatment-related AEs was similar between data from 2016 (grade 3, 52.8%; grade 4, 26.8%) and 2 years thereafter (grade 3, 54.2%; grade 4, 28.9%). Any-grade treatment-related AEs were noted in 98.6% of patients at both time-points.

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There were, furthermore, 7 further responses noted, which occurred after the primary analysis, corresponding to an objective response rate of 60.6% in the present analysis. No new grade 5 events were noted in the long-term follow-up.

“In conclusion, long-term follow-up of copanlisib demonstrated sustained and enhanced efficacy over time, including additional durable complete responses,” the authors wrote. “The AEs remained transient and manageable over time, including in those patients treated with copanlisib for more than 1 year.”


Dreyling M, Santoro A, Mollica L, et al. Long-term safety and efficacy of the PI3K inhibitor copanlisib in patients with relapsed or refractory indolent lymphoma: 2-year follow-up of the CHRONOS-1 study [published online December 23, 2019]. Am J Hematol. doi: 10.1002/ajh.25711