Updated analyses are validating the efficacy of copanlisib in the treatment of relapsed or refractory indolent B-cell lymphoma. Investigators reported at the 2017 annual meeting of the American Society of Hematology (ASH), held December 9-12 in Atlanta, Georgia, that the objective response rate was 58.5% and the median duration of response was more than 1 year in an ongoing phase II study. In addition, they reported a low rate of individual severe toxicities and the lack of late-onset toxicities with long-term follow-up (> 1 year). The investigators concluded that intermittent intravenous dosing may be optimal.
The phase II CHRONOS-1 trial showed copanlisib was highly active with an objective response rate (ORR) of 59.2% when treating patients with relapsed or refractory indolent B-cell lymphoma. At the time of the primary analysis cutoff (June 22, 2016), the median safety follow-up was 24 weeks. The safety profile was characterized by low rates of severe elevated hepatic transaminases and diarrhea or inflammatory events, as well as low rates of opportunistic infections, fatal infections, or other fatal serious adverse events. At this meeting, researchers reported on further safety and efficacy analyses based on a data cutoff on February 20, 2017 (8 months after the primary analysis).
The cohort included patients with histologically confirmed indolent B-cell non-Hodgkin lymphoma (4 subtypes: follicular, marginal zone, small lymphocytic, and lymphoplasmacytoid/Waldenstrӧm macroglobulinemia). All the patients had relapsed or were refractory to two or more prior lines of therapy. For this investigation, copanlisib was administered at a fixed dose of 60 mg via 1-hour intravenous infusion on an intermittent schedule days 1, 8, and 15 of a 28-day cycle. The full analysis set comprised 142 patients (median age, 63 years) and all but one had indolent lymphoma.
The researchers found objective tumor responses were demonstrated in 83 patients (ORR, 58.5%) per independent central review compared with 84 patients (ORR, 59.2%) in the June 2016 dataset. The researchers noted there were three additional complete responses (CRs) and 20 in total (14.1%). Two of the additional CRs were in follicular lymphoma patients (16.4%) and one was in a patient with marginal zone lymphoma (13%).
The median duration of response was 12.2 months (range, 0.03-28.1 months) and the median progression-free survival was 11.3 months (range, 0.03-30 months). The updated analysis showed that worst-grade adverse events (AEs) had not changed despite the longer safety follow-up. The most common treatment-emergent AEs (all-grade) included transient hyperglycemia (49.3%) and transient hypertension (29.6%).
Medical oncologist Laurie Sehn, MD, MPH, a clinical assistant professor with the BC Cancer Agency and University of British Columbia in Canada, said these data are reassuring for clinicians. Dr. Sehn, who is also the Associate Editor of Blood, said it is paramount that patients are closely monitored on this agent to make sure there are no significant late-onset toxicities with long-term follow-up. "Results from this updated safety analysis of copanlisib in relapsed/refractory patients with indolent lymphoma are reassuring that the toxicity profile remains favorable, with little concern for any serious cumulative toxicities based on follow-up to date,” Dr. Sehn told OncoTherapy Network.