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Ibrutinib and Idelalisib Continue to Impress in CLL, May Eventually Replace Chemotherapy for Some Patients

Gina Columbus @ginacolumbusonc
Published: Tuesday, Apr 28, 2015

As I mentioned, I think we are going to have to learn how best to dose this drug, because continuous dosing is problematic from a side effects standpoint. There is a manuscript that was recently published in Leukemia & Lymphoma regarding side-effect management, specifically the management of diarrhea. That should be a good resource for physicians. In terms of resistance, we know essentially nothing with resistance mechanisms with idelalisib to date.

What other significant research in CLL is being presented at the 2015 AACR Annual Meeting beyond ibrutinib and idelalisib?

There is a tremendous amount of new data being presented at this meeting. Of course, there are some preclinical studies with different types of compounds and different targets. However, there is nothing that has really risen to the level of “this is the next best thing.” We’re not seeing a lot at the clinic, at least at this meeting.

As the role of targeted therapies continues to grow, what do you see as the future role of chemotherapy in treating CLL?

The role of chemotherapy, or chemoimmunotherapy, in CLL is going to be very interesting. A lot of patients are really not interested in that at all, and I predict that will only accelerate because of the efficacy and tolerability of these novel agents. Currently, we are conducting randomized trials in the frontline setting compared to our standard therapies. Once those results come out, and if they are positive with respect to the novel agents, that will only accelerate the trend toward no chemoimmunotherapy.

It would be a remarkable accomplishment if you can have the average CLL patient who, needs their initial therapy and is in their mid-70s, starts a therapy that is oral and well tolerated. Even if it does not eliminate their disease, it could manage it for the rest of their natural life. I think that is a tremendous accomplishment.

Can you discuss the progress of integrating novel CLL agents into the frontline setting?

In the frontline setting there is obinutuzumab, an anti-CD20 antibody that does have an indication in combination with chlorambucil. There will be studies, and our studies, that are looking at obinutuzumab in combination with some of these newer oral agents. For example, there is another investigational drug called ABT-199, which is an oral Bcl-2 inhibitor. That is being used in combination with obinutuzumab in the frontline setting.

We have a variety of trials using ibrutinib, or ibrutinib plus anti-CD20 antibodies in frontline studies, as well as idelalisib in frontline studies. Ofatumumab has been around for quite awhile in the United States as a drug for relapse patients. I do not think it is going to gain much traction in the frontline setting because of these other choices and the results that we have to date. It will be interesting to see if there is value added to the new oral agents with any of the anti-CD20 antibodies, or if we will do fine without them.

Is there anything else about managing CLL that community oncologists should be aware of?

With respect to the future of CLL, we have these types of drugs—and we’ll see more—so I think there is reason to be optimistic for the future. Other very novel therapies, such as the checkpoint inhibitors that are all the rage for solid tumors, will be investigated, possibly in combination with these approved drugs.

Also, chimeric antigen receptor (CAR) T-cell therapy in CLL should be examined. Remember, the first splash that therapy made in recent years was for refractory CLL. Now, the focus is on acute lymphoblastic leukemia, perhaps large-cell lymphoma, but efforts are still ongoing with CLL. I think in the next 2 years, we will start to get answers as to whether that can be a curative therapy for CLL.

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