CLL/SLL |MCL |MZL

AACR 2017 poster 154/21 – Copanlisib is active as monotherapy or in combination in Mantle Cell Lymphoma, Marginal Zone Lymphoma, and Chronic Lymphocytic Leukemia cell lines

This year’s American Association for Cancer Research (AACR) annual meeting took place on 1–5 April in Washington, DC, USA. The program committee Chair was Kornelia Polyak, MD, PhD, from the Dana-Farber Cancer Institute, Boston, Massachusetts.

On Sunday 2nd April, a poster (154 / 21) by Eugenio Gaudio, from the Institute of Oncology Research, Bellinzona, Switzerland, et al. titled “The phosphatidylinositol-3-kinase (PI3K) inhibitor (i) copanlisib is active in preclinical models of B-cell lymphomas as single agent and in combination with conventional and targeted agents including venetoclax and palbociclib” was presented.

Multiple MCL, MZL, and CLL cell lines were exposed to increasing doses of copanlisib alone and in combination with other compounds using a fixed ratio set-up.

Key Highlights:
  • Copanlisib showed anti-tumor activity in the majority of cell lines (median IC50 = 22nM; 95% CI, 15–98)
  • The other most efficacious drugs = bortezomib (5nM; 5–7), romidepsin (34nM; 2–94), roniciclib (23nM; 18–29), panobinostat (161nM; 11–1263), and MI2 (490nM; 224–1,000)
  • The remaining had median IC50s >500nM
  • Combinations with venetoclax and palbociclib were the most promising, achieving CI values <0.5 in 7 and 6 cell lines, respectively
  • Gene expression profiling before treatment identified gene sets associated with sensitivity to these two combinations
  • Low expression of cell cycle genes as well as high expression of genes involved in interferon signaling, oxidative phosphorylation, fatty acid metabolism, apoptosis, PI3K/AKT/mTOR, and IL6/JAK/STAT signaling were associated with synergism to copanlisib/venetoclax
  • The palbociclib combination was more active with high expression of E2F/MYC targets and cell cycle genes and low expression of genes involved in IFN PI3K/AKT/mTOR and IL6/JAK/STAT signaling

The poster concluded by stating that copanlisib is active in MCL, MZL, and CLL cell lines. Combinations with venetoclax (BCL-2 inhibitor) and palbociclib (CDK4/CDK6 inhibitor) were the most synergistic. Using gene expression profiling may identify patients with Lymphoma who would respond well to these combination regimens.

Reference:

1. Gaudio E. et al. The phosphatidylinositol-3-kinase (PI3K) inhibitor (i) copanlisib is active in preclinical models of B-cell lymphomas as single agent and in combination with conventional and targeted agents including venetoclax and palbociclib [Poster]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; 2017. Poster nr [154 / 21].