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Near the end of the ASH 2015 meeting in Orlando, Dr. Jeff Jones, also out of OSU, presented his data on combining the BCL-2 ( B-cell lymphoma-2) inhibitor venetoclax with the antibody obinutuzumab, the ongoing European trials and a new study that adds ibrutinib to that mix in an attempt to move us closer to that good “C” word: CURE.
Take Away Points
- It is not clear whether adding a monoclonal antibody to the newly approved BCR (B-cell receptors) inhibitors such as ibrutinib or idelalisib makes a difference in the long-term outcomes.
- Obinutuzumab (Gazyva), a third generation monoclonal antibody, already has proven to be more effective than rituximab when combined with the old school chlorambucil, and now is shown to add efficacy to the BCL-2 inhibitor, venetoclax (aka ABT-199 or GDC-0199). See this published article for more details.
- There was a 100% response rate in treatment-naïve patients treated with the combination of obinutuzumab and venetoclax. Almost ¼ of the patients had a complete response.
- Although not a cytotoxic chemotherapy, venetoclax acts more like one with its rapid clearing of CLL cells compared to the slower way that the BCR inhibitors work.
- Several ongoing and upcoming trials are studying combinations that include venetoclax plus an antibody, but no chemotherapy, as the backbone of therapy.
What we all want is a cure for CLL and it is most unlikely that we are going to get there with a single agent, so we need to look at combinations. The “gold standard” chemo-immunotherapy (CIT) combination of FCR (fludarabine, cyclophosphamide, and rituximab) has provided very durable responses for a select group of low-risk patients that to some researchers is starting to look like a cure.
But for the vast majority of us, with FCR or any CIT, we will always relapse, usually with more aggressive disease, so we need a better option.
Now that we have several new non-chemo drugs, both approved and in development, that work well and in different ways, the next step is to do the trials to find out which combinations are safe and most effective.
As Dr. Jones says: It’s all good.
Here is a link to the obinutuzumab and venetoclax trial referenced by Dr. Jones.
Please enjoy my short interview with Dr. Jeff Jones from a very hectic ASH 2015.
Brian Koffman, MD March 28, 2016