Ibrutinib Trial Results

The latest issue of the journal Blood has the results of a phase 2 trial for Ibrutinib in Follicular Lymphoma patients with relapsed or refractory disease (that is, their FL has returned or had gotten worse). The results are kind of mixed, but with some interesting things worth thinking more about.

First, a reminder about what Ibrutinib is and does. It is classified as a Bruton Tyrinase Kinase inhibitor. BTK is an enzyme that is necessary for a bunch of processes in a cell to happen that let the cell grow and divide. When it gets out of control bad things happen (like cancer, since that growth and dividing doesn't stop when it should). By inibiting (or stopping) BTK, Ibrutinib shuts down that uncontrolled growth of the cancer cells.

The results are reported in the article called "Single-agent Ibrutinib in Relapsed or Refractory Follicular Lymphoma: A Phase 2 Consortium Trial." The phase 1 trial was successful enough to trigger the phase 2, which involves only FL patients -- 40 of them, in the United States, Canada, and Singapore. The results were not as good as those in the phase 1 trial, or as good as Ibrutinib in some other types of lymphoma: an Overall Response of 37.5%, with a Complete Response in 12.5%.

But the study went a little deeper than just looking at Response rates.

The researchers also paid attention to three other things: whether or not a PET scan predicted a response, whether any biomarkers could predict response, and whether or not patients with a Response were sensitive to Rituxan.

For the PET scans, 20 patients were given scans after 8 days of Ibrutinib. Researchers found that a particular SUV (Standardized Uptake Value -- a measurement of how active the cancer cells are) predicted whether patients would have a response. This is important -- because Ibrutinib is taken for a long period, it would be helpful to know in that shorter time whether it is likely to work.

The second thing they looked for involved genetic biomarkers. 31 patients were given a fine needle biopsy before they started the treatment. Patients with mutations of a gene called CARD11 did not respond to Ibrutinib. This, again, is important -- by identifying a biomarker like this before the treatment is given, it can eliminate certain patients from wasting the time and money trying something that won't work.

Finally, the researchers looked at whether or not patients were refractory to Rituxan -- that is, Rituxan had stopped working for them. Patients who were refractory to Rituxan had a much lower response rate to Ibrutinib than those who weren't: 16.7% to 52.6%. Again, this could be an important way to eliminate certain patients from trying Ibrutinib.

The journal also published a commentary on the study called "Choosing Ibrutinib Wisely." I found this to be particularly helpful in understanding the Ibrutinib study's significance. While the results were "modest" in terms of Response rates, and the study was pretty small, it still tells us a lot, and kinase inhibitor seem to have a place for FL patients, particularly those who are relapsed or refractory (rather than patients receiving their first treatment).

And while Ibrutinib had "modest" results on its own, there are still some trials that look at Ibrutinib in combination with Rituxan that have much higher Response rates (around 80%, give or take a few percentage points). And other kinase inhibitors are being studied that seem to improve upon earlier ones like Ibrutinib.

So while the numbers seem low at first glance, the study, in the end, seems very successful in what it has taught researchers. There seems to be a lot here that would be worth exploring further in a larger study.

Don't count Ibrutinib out yet.....