Copanlisib for the treatment of adults with relapsed follicular lymphoma

ABSTRACT

Introduction

Follicular lymphoma (FL) is the second most common histotype of lymphoma and is considered an incurable disease. The need for new treatment options has led to the development of innovative targeted agents, including inhibitors of the phosphatidylinositol-3-kinase (PI3K) pathway.

Areas covered

Copanlisib, an intravenous pan–class I PI3K inhibitor, has been approved by the US Food and Drug Administration (FDA) for the treatment of relapsed FL in patients who have received at least two prior systemic therapies. In this article, we critically review the mechanism of action, clinical efficacy, safety, dosage, administration, and role of copanlisib in the treatment of relapsed FL.

Expert opinion

Treatment with copanlisib results in clinically relevant and durable responses in heavily pretreated patients with relapsed or refractory FL. In addition, copanlisib has a manageable safety profile in this population, with low rates of severe hepatic transaminitis, diarrhea, colitis, and noninfectious pneumonitis. Further investigations of copanlisib within combination regimens will potentially allow to move copanlisib to an earlier line of therapy for FL. However, results of the CHRONOS-4 clinical trial evaluating copanlisib with standard chemoimmunotherapy (rituximab with bendamustine or CHOP) are not yet available.

KEYWORDS:

• Follicular lymphoma
• PI3K inhibitor
• copanlisib
• chemoimmunotherapy
• treatment

Article highlights

• Patients with relapsed follicular lymphoma (FL) have a wide range of treatment options, including PI3K inhibitors. The PI3K pathway is known to promote cellular survival and play a role in developing resistance to current chemotherapy. To date, three different PI3K inhibitors have been approved in the USA for the treatment of FL: idelalisib, copanlisib, and duvelisib.

• Idelalisib, a delta isoform-specific PI3K, was the first to receive United States Food and Drug Administration (FDA) approval based on data in third-line treatment of FL and low-grade lymphoma. This oral agent achieved a response rate of 57%, including a 6% rate of complete remissions (CRs) with a median progression-free survival (PFS) of 11 months. Duvelisib is an oral agent and dual inhibitor of PI3Kδ and PI3Kγ that has shown positive phase III results.

• Most recently, copanlisib, an agent with inhibitory activity predominantly targeting the alpha and delta isoforms of PI3K, was granted accelerated approval by the FDA on the basis of its activity in the third-line treatment of FL, copanlisib represents a specific PI3K inhibitor that has effects on four isoforms of the PI3K protein. As monotherapy for the treatment of iNHL, copanlisib has showed encouraging results and acceptable toxicity profile. We expect copanlisib will remain an agent of clinical significance. Further investigations as combination therapy will potentially push copanlisib to an earlier line of therapy for the iNHL. The results of the CHRONOS-4 clinical trial, which combines copanlisib with standard chemoimmunotherapy (B-R or R-CHOP) are eagerly awaited.

• The aim of this paper is to review the mechanism of action, clinical efficacy, safety, dosage, administration and role of copanlisib in the treatment of relapsed FL.

Acknowledgments

Editorial assistance was provided by Luca Giacomelli, PhD, Barbara Bartolini, PhD and Aashni Shah (Polistudium SRL, Milan, Italy); this assistance was supported by internal funds.

Declaration of interest

A. Santoro has served as an advisory board member for Bristol-Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer and Merck Sharp Dhome; as a consultant for Arqule/Sanofi; has received a speaker’s bureau from Takeda, Bristol-Myers Squibb, Roche, Abbvie, Amgen, Celgene, Servier, Gilead, AstraZeneca, Pfizer, Arqule, Lilly, Sandoz, Eisai, Novartis, Bayer and Merk Sharp Dhome.

C.C. Stella has received Speaker’s bureaus from Bristol-Myers Squibb, Merk Sharpe Dohme, Amgen, Janssen Oncology; and served as a paid consultant for Sanofi, ADC Therapeutics, Servier, Boehringer, Ingelheim, Novartis, Roche Genenta Science srl and Rhizen Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosure

A reviewer of this manuscript has disclosed that they are a co-author of a registration study cited in the manuscript. Peer reviewers on this manuscript have no other relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.