At ASH 2018, Dr. Matt Davids from Dana Farber Cancer Institute shared some news on duvelisib, the first dual PI3KƔ and ∆ inhibitor that is now approved as third line in relapsed and refractory CLL.
- The DUO trial already proved that the oral med, duvelisib was significantly superior to ofatumumab leading to its approval in relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two prior therapies.
- PI3K inhibitors effectively block the B cell receptor leading to excellent control of the CLL, but in a different way than a BTK inhibitor such as ibrutinib.
- It is not yet known if the dual PI3KƔ and ∆ inhibition is important compared to idelalisib that only inhibits PI3K∆..
- The trial design allowed for crossover, the only ethical way to do a trial. What that means is that if patients progress on one arm of the trial, they can then switch to the other therapy to see if that works. This was not allowed at first in a similar trial (RESONATE) that compared ibrutinib to ofatumumab. Please take a look at this important issue from the perspective of Dr. O’Brien in this interview.
- 3 of 4 of the 90 patients responded when crossed over to duvelisib with an average 15 months progression free survival in this heavily pretreated group with few options.
- The most common severe (≥ Grade 3) hematologic side effects included low neutrophil count (23%) and low platelets (4%).
- The most common severe non-hematologic adverse events included diarrhea (21%), pneumonia (12%), and colitis (11%).
- Nine pts had adverse events with a fatal outcome with 1 assessed as related to treatment (PJP or pneumocystis jirovecii pneumonia, a serious infection that hits those with impaired immunity).
- PI3K inhibitors do have significant side effects but duvelisib does seem less likely to cause serious liver inflammation. The other side effects are as expected but we have learned from the prior experience with idelalisib and so are now better prepared and are quicker to manage them. This is particularly true for any diarrhea or colitis that begins months after therapy has begun. When management is prompt and appropriate, patients usually do fine, so tell your doctor if you are having any gut issues with this med!
- There are promising open combination trials such as this that use venetoclax with duvelisib for CLL.
The PI3K inhibitors are very active in CLL and the side effects can generally be managed if properly reported and promptly handled. Duvelisib will likely play some role in CLL therapy, quite possibly in combinations with other agents. Trials with duvelisib combinations are ongoing now.
It’s good to have options.
Here is the link to the ASH abstract:
Here is my video interview from ASH 2018 with Dr. Matt Davids:
We are all in this together.