ASH 2015: Dr. Stephan Stilgenbauer on Dramatic Responses to Venetoclax in relapsed/ refractory (R/R) 17p deleted CLL

In the final session of my three ASH 2015 interviews with Dr. Stephan Stilgenbauer out of the University of Ulm, he discusses his late breaking abstract on venetoclax in refractory chronic lymphocytic leukemia (CLL) patients with deletion 17p. This is a tough group to treat. I should know. I was one of them until I entered my clinical trial of PCI-3275, now known as ibrutinib.

TAKE AWAY POINTS

• Venetoclax (ABT-199) is an oral agent that turns on a potent CLL suicide (apoptosis) pathway. It does this by inhibiting BCL-2 that CLL cells have very successfully used to survive when they shouldn’t, but BCL-2 is not an important survival driver in normal cells.
• Unlike ibrutinib and idelalisib, it works very quickly, with most responses seen in less than a month.
• 4 out of 5 R/R 17p deleted patients responded, with >20% of the responses being MRD (minimal residual disease) negative which means that less than 1/10,000 cells is one of the CLL clone and represents the deepest possible response.
• Prior serious issues with tumor lysis syndrome (TLS) are now well controlled.
• It is generally easy to take, but side effects included:
  • Neutropenia (43%)
  • Diarrhea (29%)
  • Nausea (29%)
  • Anemia (27%)
  • Fatigue (22%)
  • Infection ≥ grade 3 (20%)

These results are outstanding and, although the data is very preliminary and needs to be confirmed in larger and longer trials, it is very exciting. As a result of these data, the abstract “Venetoclax (ABT-199/GDC-0199) Monotherapy Induces Deep Remissions, Including Complete Remission and Undetectable MRD, in Ultra-High Risk Relapsed/Refractory Chronic Lymphocytic Leukemia with 17p Deletion: Results of the Pivotal International Phase 2 Study” nabbed one of the hard to get spots at ASH reserved for late breaking abstracts.

Here is the last of my three-part interview from ASH in December 2015 with Dr. Stilgenbauer.

Brian Koffman, MD  3/21/16