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MCL: Long-Term Safety/Efficacy Data With Ibrutinib

Insights From: Bijal D. Shah, MD, H. Lee Moffitt Cancer Center & Research Institute; Lauren C. Pinter-Brown, MD, UCI Health; Eduardo Sotomayor, MD, GW Cancer Center
Published: Monday, Feb 04, 2019



Transcript:

Eduardo Sotomayor, MD:
At ASH [the American Society of Hematology Annual Meeting & Exposition] last year, there was a presentation about a long-term follow-up of patients with relapsed/refractory mantle cell lymphoma on ibrutinib. There were 3 clinical trials in which we put together the patients with follow-up. It was a very good design for a study; it’s 2 years of follow-up.

The data show that in those patients who achieved complete response with ibrutinib as the first therapy after the first relapse do well. Also what we learned from that study is in patients with relapsed/refractory mantle cell lymphoma, if you used ibrutinib at first relapse, it’s going to be better than second, third, or multiple relapses. And that is very important because that is helping us to understand that here we have a new drug with a new method of action that is different from chemotherapy, and the earlier you use it in the relapsed setting, the better the patients are going to do.

And the other measure about the clinical trials is now we are seeing 3 years’ follow-up. Also, what we are seeing with long-term follow-up is that with most of the adverse effects associated with ibrutinib, you are going to see them during the first year. And this is that the patient’s body gets used to it, and then the patients are able to continue with treatment.

And I think it is putting this in perspective when we are seeing any targeted agent. We all get excited, and we get excited about great overall response rate, great complete response. But I think it’s important to let the data mature 1, 2, or 3 years and then have what is a real progression-free survival. Are we impacting overall survival with a good quality of life? Remember, mantle cell lymphoma is in an elderly population. And that’s what I always tell my fellows, my students. So we are dealing with an elderly population—geriatric. This is important. And then based on that, you make a decision. But we need to be careful because we don’t want to achieve a complete response if the patient is going to be affected in the case of their quality of life.

Bijal D. Shah, MD: What’s really nice about the long-term safety data with ibrutinib is we’re not seeing anything radically new coming up. We knew about the bruising, the contusions, and the atrial fibrillation. We had a good feel for this really from the pivotal frontline phase II trial. You could argue that maybe we’re seeing a little bit in the way of atrial fibrillation events, but I’m not seeing anything that has me overwhelmingly concerned. I think that it is important to keep in mind that ibrutinib can be associated with cytopenias, particularly with longer use. And what we’ve seen at our center has mainly been thrombocytopenia, and that can make it a little bit challenging at times to dose the ibrutinib. It may require dose reductions and other things that we have to address.

The other thing with ibrutinib is recognizing the risk of infection. It seems as if it’s an earlier event for most patients, meaning within the first 6 months or so after starting therapy. But you have to be vigilant, and I’ll just leave it at that. There can be infections that are atypical that you wouldn’t otherwise expect, and so you just have to keep that in the back of your mind. And when I say atypical infections, you may see things like CMV [cytomegalovirus], you may see things like PJP [Pneumocystis jiroveci pneumonia], you may see these weird infections that you wouldn’t otherwise have expected. I don’t want to belabor that. These are patients who have seen prior chemotherapy, whose immune systems may not be entirely normal before going into therapy. Now, on top of that, having mantle cell lymphoma, which may also, like CLL [chronic lymphocytic leukemia], come with IL-10 autocrine production that may also further suppress immune function. There are a variety of things that are influencing possibly this infection data point, but it’s just something important that I wanted to make sure I stress.

Transcript edited for clarity.
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Transcript:

Eduardo Sotomayor, MD:
At ASH [the American Society of Hematology Annual Meeting & Exposition] last year, there was a presentation about a long-term follow-up of patients with relapsed/refractory mantle cell lymphoma on ibrutinib. There were 3 clinical trials in which we put together the patients with follow-up. It was a very good design for a study; it’s 2 years of follow-up.

The data show that in those patients who achieved complete response with ibrutinib as the first therapy after the first relapse do well. Also what we learned from that study is in patients with relapsed/refractory mantle cell lymphoma, if you used ibrutinib at first relapse, it’s going to be better than second, third, or multiple relapses. And that is very important because that is helping us to understand that here we have a new drug with a new method of action that is different from chemotherapy, and the earlier you use it in the relapsed setting, the better the patients are going to do.

And the other measure about the clinical trials is now we are seeing 3 years’ follow-up. Also, what we are seeing with long-term follow-up is that with most of the adverse effects associated with ibrutinib, you are going to see them during the first year. And this is that the patient’s body gets used to it, and then the patients are able to continue with treatment.

And I think it is putting this in perspective when we are seeing any targeted agent. We all get excited, and we get excited about great overall response rate, great complete response. But I think it’s important to let the data mature 1, 2, or 3 years and then have what is a real progression-free survival. Are we impacting overall survival with a good quality of life? Remember, mantle cell lymphoma is in an elderly population. And that’s what I always tell my fellows, my students. So we are dealing with an elderly population—geriatric. This is important. And then based on that, you make a decision. But we need to be careful because we don’t want to achieve a complete response if the patient is going to be affected in the case of their quality of life.

Bijal D. Shah, MD: What’s really nice about the long-term safety data with ibrutinib is we’re not seeing anything radically new coming up. We knew about the bruising, the contusions, and the atrial fibrillation. We had a good feel for this really from the pivotal frontline phase II trial. You could argue that maybe we’re seeing a little bit in the way of atrial fibrillation events, but I’m not seeing anything that has me overwhelmingly concerned. I think that it is important to keep in mind that ibrutinib can be associated with cytopenias, particularly with longer use. And what we’ve seen at our center has mainly been thrombocytopenia, and that can make it a little bit challenging at times to dose the ibrutinib. It may require dose reductions and other things that we have to address.

The other thing with ibrutinib is recognizing the risk of infection. It seems as if it’s an earlier event for most patients, meaning within the first 6 months or so after starting therapy. But you have to be vigilant, and I’ll just leave it at that. There can be infections that are atypical that you wouldn’t otherwise expect, and so you just have to keep that in the back of your mind. And when I say atypical infections, you may see things like CMV [cytomegalovirus], you may see things like PJP [Pneumocystis jiroveci pneumonia], you may see these weird infections that you wouldn’t otherwise have expected. I don’t want to belabor that. These are patients who have seen prior chemotherapy, whose immune systems may not be entirely normal before going into therapy. Now, on top of that, having mantle cell lymphoma, which may also, like CLL [chronic lymphocytic leukemia], come with IL-10 autocrine production that may also further suppress immune function. There are a variety of things that are influencing possibly this infection data point, but it’s just something important that I wanted to make sure I stress.

Transcript edited for clarity.
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