Meet-the expert: Treatment of AML

Questions and Answers with Prof. G.J. Ossenkoppele

Which are the today most important unmet clinical needs in AML?

• Improving CR rate in elderly AML.
• Preventing relapse in elderly and younger AML.
• Approval of new promising drugs.
• Determine who is fit for intensive treatment.

Which are the most promising new drugs for the treatment of AML?

• FLT3-ITD inhibitors (midostaurin, quizartib).
• Hypomethylating agents (HMAs) and new “second generation” HMAs.
• Vosaroxin (topoisomerase II inhibitor).
• Bcl-2 inhibitors (venetoclax).
• CRM 1 inhibition (selinexor).

Which were the most exciting news from the recent ASH Meeting ?

• Positive outcome  in the Phase III  RATIFY study in FLT3-ITD/TKD mutated patients of midostaurin added to standard therapy.
• Promising combinations in addition to HMAs (i.e. azacytidine plus pracinostat).

How far is a really targeted therapy for AML (apart APL) ?

• Not so close because of the heterogeneity of AML; FLT3ITD is the first example although midostaurin is not very specific.

Has immunotherapy a future in AML ?

• Absolutely, allogeneic stem cell transplantation has already been an example for many years. But new modalities are emerging:
  • monoclonal antibodies (anti-CD33, anti-CD123, and anti-CD47)
  • immunoconjugates
  • BiTEs (anti-CD33, anti-CLEC12A)
  • CARTs will soon be explored in AML
  • Immune checkpoint inhibitors.

Gert J.Ossenkoppele, M.D., PhD., is Professor of Hematology at the VU University Medical Center, Amsterdam, The Netherlands.