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At the ASH (American Society of Hematology) Annual Conference in Atlanta in December 2017, Dr. Ian Flinn from Sarah Cannon Cancer Institute, Nashville, TN presented new data on a registration trial of duvelisib versus ofatumumab for the treatment of chronic lymphocytic leukemia (CLL).
This is the large trial that compares a new therapy, in this case duvelisib to an established standard of care, ofatumumab, to prove benefit and hopefully lead to the drug’s approval.
Duvelisib is an experimental PI3K inhibitor that has broader activity than the approved PI3K inhibitor, idelalisib (Zydelig).
Ofatumumab (Arzerra) is a second generation, fully humanized monoclonal antibody targeting CD20 that is engineered to attack and kill CLL cells. It was the second anti-CD20 monoclonal antibody approved to treat CLL, rituximab (Rituxan) being the first and obinutuzumab (Gazyva) being the third. It is approved to treat CLL and was the also comparator in the trial that lead to the ibrutinib approval.
This is my interview with Dr. Flinn on his presentation of the important results from this study treating relapsed/refractory chronic lymphocytic leukemia patients.
Take Away Points:
- B cell signaling is important in B cell survival and blocking it by inhibiting PI3K has powerful therapeutic benefits in CLL.
- There are several different types or isoforms of PI3K.
- Idelalisib inhibits PI3K-δ and has proven very effective in treating CLL.
- Duvelisib (DUV) is an oral dual inhibitor of PI3K-δ and PI3K-γ that is taken orally twice daily.
- Inhibiting PI3K-γ may have a benefit in treating the microenvironment that protects the CLL cells.
- Mean or average progression free survival (PFS) was more than a year with duvelisib, compared to only 9 months for ofatumumab.
- Side effects were as expected with a PI3K inhibitor such as diarrhea, colitis and infections that could be managed and reduced with appropriate vigilance and prophylactic antibiotics
Here is a link to the abstract.
You can watch my interview with Dr. Flinn below, or read the transcript here.
In summary, odds are good we will soon have another potent oral agent to treat CLL. The trial is similar to the one that lead to the approval of ibrutinib, but that was a few years ago and it is possibly the FDA may raise the bar to get this approval.
Another treatment option is always a good thing so I am hoping for an approval soon.
Brian Koffman, MD 1/16/18