Dr. Constantine Tam from Peter McCallum in Melbourne Australia has led pioneering research on important new drugs to treat chronic lymphocytic leukemia (CLL).
At ASH 2017, we discussed an experimental BTK blocker, BGB-3111, now with the name zanubrutinib, that helps control CLL by shutting down the B-cell receptor (BCR), similar to the activity of two approved CLL drugs that block BCR, ibrutinib (by blocking BTK) and idelalisib (by blocking Pi3K). What BGB-3111 promises is a more selective inhibition of BTK. As with another more selective BTK blocker, acalabrutinib, this might result in fewer adverse events and easier and better combinations with other medications, especially rituximab.
Key Take Aways:
- BGB-3111 (zanubrutinib) is a new BTK inhibitor.
- It is more selective and better absorbed than ibrutinib.
- Adding rituximab to ibrutinib doesn’t add efficacy.
- Adding obinutuzumab to BGB-3111 resulted in 35% complete response (CR) rates in frontline and 20% CR in relapsed refractory CLL patients. Whether this is due to the stronger potency of obinutuzumab compared to rituximab, or to the difference between the BTK inhibitors is not clear at this point.
- The strong infusion reaction often seen with obinutuzumab is seen less frequently with the prior administration of zanubrutinib. The amelioration of this adverse event is probably true with any and all BTK inhibitors.
Here is my interview with Dr. Con Tam. You can also read the transcript here.
Here is the link to the abstract on monotherapy BGB-3111 in non CLL patients.
Here is the abstract on the combination of BCG-3111 and obinutuzumab.
Here is the final abstract mentioned on checkpoint inhibitors and zanubrutinib.
For more background on checkpoint inhibitors, see this interview with Dr. John Pagel.
Having more treatment choices in the near future and drugs that are potentially easier to combine is good news for CLL patients. I look forward to more studies with zanubrutinib, especially in combinations.
Brian Koffman, MD 3-13-18