Initiation and Discontinuation of Ibrutinib in Chromic Lymphocytic Leukemia (CLL)
I was surprised by Dr. Byrd's hesitancy about using ibrutinib frontline.
I was not surprised by the lack of unaminity among the experts.
Here are some of the key points.
- The immunological modulation effects of ibrutinib are emphasized by Dr. Byrd. It is doing more than interfering with B cell signaling. Same may be true for idelalisib.
- The future is combination therapies, but what do we do now? Ibrutinib is approved as monotherapy. (That is why we need more trials.)
- Dr. Furman points out that some Imbruvica patients are continuing to improve 4 or 5 years down the line, getting to CR and even MRD negative.
- Dr. Kipps doesn't buy we ever get MRD negative if one uses the most sensitive tests, especially in the bone marrow.
- No-one really knows when to stop therapy.
It seems there are three potential visions of how things may play out.
Below, I have grossly oversimplified the three doctors' nuanced perspectives to highlight the wide spectrum of opinions about what may come to pass with the new CLL agents.
- Dr. Furman talks about a significant subset of patients that tolerate ibrutinib therapy well and continue to improve over long period of time, and so we argues why rock the boat and stop therapy, at least outside a clinical trial.
- Dr. Kipps and I agree that you can't get to CURE without passing by MRD negative first, and he wants to be able to stop therapy because the cancer has been once and for all eradicated.
- Dr. Byrd offers a slightly different possible outcome. Treat to get to MRD negative (likely with a combo), stop therapy, and then a very very long durable remission, maybe never requiring more treatment.
As Neils Bohr, the Nobel prize winning quantum physicist said: Prediction is very difficult, especially about the future.