At the 24th European Hematology Association Annual Congress in Amsterdam, Holland held in 2019, I interviewed Dr. Alexey Danilov of Oregon Health & Science University about a phase 2 trial of Entospletinib + Obinutuzumab for relapsed or refractory CLL (chronic lymphocytic leukemia).
The number of patients was small, but the results were encouraging.
- Entospletinib is a SYK (Spleen tyrosine kinase) inhibitor.
- SYK is involved in the activation of the B-cell receptor (BCR). Blocking BCR with ibrutinib through BTK inhibition or idelalisib or duvelisib, both though PI3K inhibition has revolutionized the care of CLL.
- Entospletinib blocks BCR upstream from where the approved BTK or PI3K inhibitors works.
- CLL cells are addicted to BCR activation and blocking it leads to the cancer cells leaving their protective niches in the nodes and marrow.
- In this trial, entospletinib was combined with the potent anti CD20 monoclonal antibody, obinutuzumab that is already approved in CLL.
- All patients saw their lymph nodes shrink and 14 of 17 met the requirement of being responsive.
- As with the other drugs effecting BCR, the responses tended to be shallow at first, but there were 3 complete responses and 2 patients had undetectable minimal residual disease (U-MRD), which is very promising and not usually seen with these types of therapy.
- Side effects were managed and different with no atrial fibrillation or high blood pressure or muscle pains or lung inflammation or bleeding and bruising issues, but elevated liver enzymes were seen.
- The combination did allow a fixed duration of therapy, in other words, both drugs could be stopped.
The study is too small and the follow-up too short, but it is encouraging to see a new combination that is so active in chronic lymphocytic leukemia and has different and so far, manageable side effects when compared to the available drugs
Here is my interview with Dr. Daniolov from EHA 2019:
Here is the EHA abstract:
Brian Koffman MDCM (retired)