PurposePhosphatidylinositol 3-kinase (PI3K) signaling is critical for the proliferation
and survival of malignant B cells. Copanlisib, a pan-class I PI3K inhibitor with predominant
activity against PI3K- and - isoforms, has demonstrated efficacy and a manageable
safety profile in patients with indolent lymphoma.Patients and MethodsIn this phase
II study, 142 patients with relapsed or refractory indolent lymphoma after two or
more lines of therapy were enrolled to receive copanlisib 60 mg intravenously on days
1, 8, and 15 of a 28-day cycle. The primary end point was objective response rate;
secondary end points included duration of response, progression-free survival, and
overall survival. In addition, safety and gene expression were evaluated.ResultsMedian
age was 63 years (range, 25 to 82 years), and patients had received a median of three
(range, two to nine) prior regimens. The objective response rate was 59% (84 of 142
patients); 12% of patients achieved a complete response. Median time to response was
53 days. Median duration of response was 22.6 months, median progression-free survival
was 11.2 months, and median overall survival had not yet been reached. The most frequent
treatment-emergent adverse events were transient hyperglycemia (all grades, 50%; grade
3 or 4, 41%) and transient hypertension (all grades, 30%; grade 3, 24%). Other grade
3 events included decreased neutrophil count (24%) and lung infection (15%). High
response rates to copanlisib were associated with high expression of PI3K/B-cell receptor
signaling pathway genes.ConclusionPI3K- and - inhibition by copanlisib demonstrated
significant efficacy and a manageable safety profile in heavily pretreated patients
with relapsed or refractory indolent lymphoma.
