At the 2014 American Society of Hematology meeting, Dr. Jan Burger from the MD Anderson Cancer Center presented some of the findings from trials examining the combination of rituximab (Rituxan) and ibrutinib (Imbruvica) in the treatment of chronic lymphocytic leukemia (CLL) an oral signal blocker that has strong activity against even high-risk CLL.
Take Away Points:
- Adding rituximab to ibrutinib speeds response rates and elicits deeper remissions.
- There is still an open Phase 2 trial to determine if adding rituximab to ibrutinib actually improves progression-free survival (PFS).
- In the test tube, ibrutinib may partial block the activity of rituximab, but that doesn’t seem to be an issue in the trials.
- Three potential paths forward:
- Non-chemo cocktails
- Chemo and non-chemo cocktails
- Sequential treatment starting with chemo and then adding non-chemo
Dr. Burger and I discussed whether adding rituximab, a well-known monoclonal antibody that seems to improve outcomes when added to other therapies will really improve CLL treatment outcomes in the long run. One concern is that the results are already very good with ibrutinib alone and the depth of response may continue to improve over years, suggesting that rituximab’s perceived benefit may be only an acceleration of the response and is thus “cosmetic”, adding no real long-term improvements at the cost of some significant increased expense, inconvenience and risk.
The other question is whether ibrutinib might interfere with rituximab’s antibody-dependent cell-mediated cytotoxicity or ADCC that we reference. This is the important way rituximab works to kill antibody-tagged cancer cells, by recruiting immune cells in the blood stream to the cancer cells in order to attack and kill the cancer. Newer antibodies such as obinutuzumab or Gazyva may use different mechanisms to clear the cancer. See my blog post from ASH 2103 with Dr. Jennifer Brown on obinutuzumab. For more background on the differing types of monoclonal antibodies, please also see my interview with Dr. Kipps from my blog posted here.
The trial is being done to sort out these important questions. The encouraging early trial data presented at ASH 2014 can be found here.
Ofatumumab or Arzerra and ublituximab (TG-1101) also kill using the same ADCC, but may be more potent than rituximab.
The clinical trial that Dr. Burger describes can be found here and is still accepting patients.
A similar trial with ublituximab paired with ibrutinib can be found here.
I myself was on a trial of ibrutinib and ofatumumab, and am now on the ibrutinib extension. That trial is now closed.
But many more trials with two and three drugs are coming and early results are positive.
Please give a listen to Dr. Burger from ASH 2014:
Brian Koffman 5/17/15