Copanlisib Induces Nearly 1-Year Median PFS in Heavily Pretreated Indolent Lymphoma

Bruce D. Cheson, MD

Treatment with copanlisib (Aliqopa) led to a median progression-free survival (PFS) of 11.2 months and objective response rate (ORR) of 59.2% in patients with relapsed/refractory indolent lymphoma, according to results from the phase II CHRONOS-1 trial recently published in the Journal of Clinical Oncology.

The 59.2% (84/142) ORR included complete responses in 12.0% (n = 17) of patients and partial responses in 47.2% (n = 67) of patients. An additional 30% (n = 43) of patients had stable disease.

Objective response rates were over 58% all indolent lymphoma subtypes except lymphoplasmacytoid lymphoma (LPL)/Waldenstrom macroglobulinemia (WM), wherein 1 of 6 patients with the subtype achieved an objective response with copanlisib. Among 104 patients with follicular lymphoma, the ORR was 58.65% (n = 61), including a 14.42% (n = 15) complete response rate and a 44.23% (n = 46) partial response rate.

In an interview with OncLive, Bruce D. Cheson, MD, deputy chief of hematology/oncology and head of hematology at Georgetown’s Lombardi Comprehensive Cancer Center, commented on the findings.

“The CHRONOS-1 study shows that copanlisib is a very active PI3 kinase inhibitor and we desperately need new drugs for relapsed and refractory follicular lymphoma,” said Cheson. “It is active, the responses can be durable, and the drug appears to be well tolerated, so it makes for an exciting new treatment option for patients with relapsed and refractory follicular lymphoma.”

Based on the results of the CHRONOS-1 trial, the FDA granted an accelerated approval to copanlisib in September 2017 as a treatment for patients with relapsed follicular lymphoma who have received at least 2 prior systemic therapies.

The CHRONOS-1 study accrued patients with multiple types of indolent lymphoma, including follicular lymphoma (grades 1-3a), marginal zone lymphoma, small lymphocytic lymphoma, and LPL/WM. Eligible patients had relapsed or refractory disease and failure of at least 2 prior lines of therapy.

Patients received copanlisib at 60 mg on days 1, 8, and 15, repeated every 28 days until disease progression or development of unacceptable toxicity. The primary endpoint was objective response by central review after a minimum of 16 weeks of treatment. Secondary endpoints included PFS, duration of response, overall survival, safety, and quality of life.

Data analysis included 142 patients who had a median age of 63. The median time since the most recent disease progression was 8.3 months, and the study population had received a median of 3 prior regimens. All of the patients had prior exposure to rituximab (Rituxan) and 1 or more alkylating agents, and 60.6% had disease that was refractory to the last regimen received.

Across the lymphoma subgroups, 80.3% of the patients had advanced disease (stage III or IV) at enrollment. Follicular lymphoma was the dominant lymphoma subtype, accounting for 73.2% of the study population.

Patients remained on treatment for a median duration of 22 weeks. All but a few patients had some degree of target lesion shrinkage in response to treatment with copanlisib. Patients with all lymphoma subtypes had lesion shrinkage.

The most common treatment-emergent adverse events were hyperglycemia (all grades, 50%; grade 3/4, 41%) and hypertension (all grades, 30%; grade 3, 24%). Additional grade ≥3 adverse events of note included decreased neutrophil count (24%) and lung infection (15%).

Cheson said follow-up was short, just 30 to 35 days after the last study treatment, and that can lead to unforeseen toxicities, but he said dosing and administration is the biggest issue at present.

“The drug is given weekly for 3 weeks, then a week off, then it’s given indefinitely, which is a burden on patients, particularly those who travel a distance to see their doctor,” Cheson said. “It’ll be challenging to get patients to be as compliant as you would like them to be, but I’m sure easier maintenance schedules will be developed to mitigate this problem.”

Dreyling M,, Santoro A, Mollica L, et al. Phosphatidylinositol 3-kinase inhibition by copanlisib in relapsed or refractory indolent lymphoma [published online October 4, 2017]. doi:10.1200/JCO.2017.75.4648.