As the former US Surgeon General, Dr. C. Everett Koop, famously said, “Drugs don’t work in patients who don’t take them.”
We have amazingly efficacious oral medications to treat CLL called kinase inhibitors (KI) that block critical enzymes that support the cancer cells, but intolerance can be an issue.
Ibrutinib blocks BTK, an important KI for CLL cell survival. While generally well tolerated, intolerance of ibrutinib is the leading reason for patients to discontinue. Surprisingly, it is not progression of the chronic lymphocytic leukemia.
Idelalisib that blocks another kinase, PI3-K ∆ is also very effective in CLL, but can have very serious side effects that lead to discontinuation.
For more on this research, please see this abstract from Blood.
The search for a pill to treat chronic lymphocytic leukemia that is both effective and very well tolerated is ongoing.
Dr. Danielle Brander of Duke Cancer Institute in Durham, North Carolina and I discussed new data presented at ASH (American Society of Hematology Annual Meeting and Exposition) 2017 concerning umbralisib, an experimental PI3-K ∆ inhibitor that may have a different adverse event (AE) profile than idelalisib.
Key Take Aways:
- Umbralisib (formerly known as TGR-1202) inhibits PI3-K ∆ that is important in the B cell receptor (BCR) pathway. This blocks survival signals in the CLL cells and can leads to dramatic responses.
- In this study of 22 patients all had to have been intolerant of a prior KI therapy to qualify to try umbralisib (20 intolerant of ibrutinib and 2 of idelalisib).
- Patients were followed for a median of 6 months.
- The most common serious AE was a low neutrophil count (neutropenia) in 23% (n=5).
- Common serious AEs associated with other PI3K-∆ inhibitors such as idelalisib were rare, with no patients having severe liver or lung inflammation and only 9% having diarrhea.
- Median Progression Free Survival (PFS) or the average time until the patient progresses had not been reached when the data was analyzed at 9 months.
This is a small phase 2 trial with a very short follow-up, but the results are encouraging, suggesting that umbralisib may have a different side effect profile than idelalisib, making it easier to tolerate while maintaining a similar efficacy in treating CLL.
Here is the video of my interview with Dr. Brander at ASH 2017 in Atlanta, Georgia. You can also read the transcript here.
Here is a link to the actual ASH abstract
Brian Koffman, MD 1/23/18