Dr. Matthew Davids from Dana Farber at Harvard Medical School in Boston outlines his important study that combines two targeted therapies for CLL at the 2016 American Society of Hematology annual meeting during our interview in San Diego.
One drug was ibrutinib, an approved BTK inhibitor that by blocking a critical signaling pathway in CLL cells led to remarkable responses and has changed how CLL is treated.
The other drug is a drug that is still in development, TGR-1202. It is similar to the approved drug, idelalisib, which also blocks a part of the B cell signaling pathway, in this case by blocking PI3k-Delta. TGR-1202 may prove to be less toxic than idelalisib and that would be a good thing.
Blocking the signaling pathway in our cancerous B cells has lead to dramatic responses.
Take Away Points:
- In the past, serious safety issues have occurred when two drugs that block B cell signaling have been combined, specifically entospletanib, a blocker of Syk, and idelalisib, one of the PI3K-delta inhibitors. The study documenting the unexpected and tragic toxicities can be found here.
- This was the first study combining any BTK inhibitor with any PI3k-delta inhibitor. The drugs used were ibrutinib and TGR-1202. Wisely it was set up as a Phase 1 trial to look for safety issues first.
- There were no dose-limiting toxicities (DLTs) discovered.
- Specifically there was no colitis, a problem that has been seen with idelalisib; no liver inflammation that required stopping the drugs; and none of the lung problems that plagued the prior combination.
- Response rate was an impressive 88% in a difficult to treat, relapsed and refractory population of CLL patients
This data is early and only involved 17 CLL patients. It is way too soon to say that the combination will improve outcome. However the safety of the combination is certainly encouraging after the terrible outcome with another “promising” combination.
Combination therapies as explained here and elsewhere on our website are probably the future in CLL. CLL is a smart cancer and blocking it at two points rather than at only one makes good sense.
Here is a link the abstract of the trial itself from ASH 2016 for your review.
Enjoy the video of my interview with Dr. Davids from ASH 2016 or you can or you can read the transcript HERE.
Brian Koffman, MD 3/28/17