CTA: What drives resistance to copanlisib? Would any therapy combinations potentially help to overcome resistance?
Dr Dreyling: There is not much known about the molecular mechanisms of resistance when it comes to PI3K inhibitors, so a crucial aspect of understanding what drives resistance to copanlisib would be the elucidation of mechanisms of resistance for PI3K inhibitors as a whole.
What we do know is that cases with high expression of PI3K and B cell receptor pathway displayed significantly higher response rate to copanlisib in the CHRONOS-1 trial. Further studies are, however, warranted.
CTA: Another study presented at ASH suggests that copanlisib may be particularly effective for marginal zone lymphoma. Why might this be, and did any other subgroups have a standout benefit (positive or negative)?
Dr Dreyling: The impact of copanlisib in marginal zone lymphoma was striking, with an overall response rate of 70%. We have found that the majority of these cases were nodal marginal zone lymphoma, which usually have a more aggressive clinical course than FL, so we are especially pleased to see these high response rates in the CHRONOS-1 study.
Eighty percent of responding patients were in ongoing response for up to 2 years, and the median DOR has not yet been reached, which is superior to what has been previously reported with other targeted approaches in the marginal zone lymphoma treatment landscape.
CTA: Could you discuss one or two other studies presented at ASH you think are promising for patients with NHL?
Dr Dreyling: In my opinion, the two most outstanding studies at this year’s ASH meeting were the phase 3 MURANO study of venetoclax in combination with rituximab for patients with chronic lymphocytic leukemia and the phase 3 ECHELON-1 study, which examined brentuximab vedotin plus doxorubicin, vinblastine, dacarbazine (A+AVD) as a frontline therapy vs ABVD in patients with previously untreated stage III or IV Hodgkin lymphoma.
While the MURANO trial also clearly demonstrated the superiority of targeted approaches in relapsed chronic lymphocytic leukemia with wild-type TP53, the benefit of additional brentuximab in the first-line treatment of Hodgkin lymphoma has to be discussed in a balanced way.