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The Role of Ofatumumab in the Treatment of CLL

Panelists:Alessandra Ferrajoli, MD, The University of Texas MD Anderson Cancer Center; Richard R. Furman, MD, Weill Cornell Medical College; Thomas J. Kipps, MD, PhD, UC San Diego Moores Cancer Center; Shuo Ma, MD, PhD, Northwestern University Feinberg School of Medicine, Susan M. O’Brien, MD, UC Irvine Health; William G. Wierda, MD, PhD, University of Texas MD Anderson Cancer Center
Published: Tuesday, Mar 15, 2016


Transcripts:

William G. Wierda, MD, PhD:
Ofatumumab was approved based on its activity in patients who were fludarabine-refractory and Campath (alemtuzumab)-refractory, or patients who are fludarabine-refractory with bulky nodes. Now, there's more data with ofatumumab. I wonder if Alessandra could comment on what her thoughts are on where ofatumumab fits in our toolbox of treatments for patients with CLL and what her thoughts are in terms of tolerability of that agent.

Alessandra Ferrajoli, MD: In terms of the second question, it's the easiest one to answer. In terms of tolerability, there is a little bit more of an infusion reaction with ofatumumab with respect to rituximab. However, the majority of the patients can tolerate the infusion. In terms of where it fits in the treatment landscape, definitely there is an advantage in treating with the combination of chemoimmunotherapy with ofatumumab for patients that have a relapse after rituximab therapy. I don't know whether we have solid data to show that this monoclonal antibody is superior for patients that are naïve, that have not been exposed to any CD20 monoclonal antibody. So my answer is, I'm not sure.

Susan M. O’Brien, MD: I think just one point, and you alluded to this, is that if I was going to put the three anti-CD20s in an infusion-reaction spectrum, ofatumumab would be here with rituximab. And you mentioned it was a little bit greater. But, you know, it's not substantially worse. Obinutuzumab would be over here. I would say I don't use more caution when giving ofatumumab than I would rituximab, which I think everybody gives with impunity and without even thinking twice about the toxicity. But I wouldn't say that about obinutuzumab just yet.

Alessandra Ferrajoli, MD: And the same for, possibly, cytopenias, both neutropenia and thrombocytopenia?

Susan M. O’Brien, MD: Yes.

Alessandra Ferrajoli, MD: There are data with obinutuzumab causing very prolonged thrombocytopenia more than the other two monoclonal antibodies.

William G. Wierda, MD, PhD: And the first dose of obinutuzumab is a split dose, as a standard approach, which we don't do with the other two antibodies, and I think that also does speak to the infusion-related issues.

Susan M. O’Brien, MD: You can get an infusion reaction 10 minutes into the infusion, and you can split the dose down to what you want. And we saw this with rituximab. Remember, we did use to do a split dose on rituximab. Nobody does it any more. So I think it's just silliness.

Thomas J. Kipps, MD, PhD: Well, on the risk of being silly, I think it's a good idea. And so I disagree with Susan on that. I think setting out to give 100 mg of obinutuzumab is actually not a bad thing, because if they get past 100 mg and come back the next day, it’s a relatively easy infusion. But oftentimes if you set upon and have the bag filled with the entire amount of antibody, and the patient has a very bad infusion reaction that forces you to stop treatment, you have to then stop the therapy, and obviously you have to then potentially carry it over for the next day. It just makes it more complicated.

I think that these infusion reactions can be managed, and it really depends on your infusion nurses. My full credit is to them in terms of how they manage the patient: giving the drug slowly on the first infusion after having given some glucocorticoids and watching very carefully how the patient is doing. Slowing the infusion down or stopping it altogether makes a big difference. And that first day is a long day because we do stretch it out for some time. But I feel a lot more confident going forward to give it with 100 mg the first day and then the remainder the next day. If everything is done correctly, I think that I'd just prefer that.

Susan M. O’Brien, MD: But Tom, that's because the infusion center's close. You're the one who mentioned that patients have lives, too. They don't want to come back two days in a row.

Thomas J. Kipps, MD, PhD: Well, I think it's very hard. I agree with you, but some of the patients call obinutuzumab rituximab with an attitude, and I see that. And so I tell patients to anticipate this going into it, and they brace themselves. And I say, ‘You know, we have to give it slowly, the 100 mg that first day, and if we get past this, we will be able to give all the antibody in one infusion with the next round.”

And I think they can accept it going forward for the first couple of days, being close to the infusion center. It's not a bad idea because we've had some patients develop tumor lysis syndrome–type qualities even after the first infusion of 100 mg or so. So, having that follow-up day where the patient's required to come in, I welcome that so you can more closely monitor your patient's electrolytes and everything else with hydration. In terms of my practice, I feel that this is something I prefer to do.

Richard F. Furman, MD: One of the interesting features about the infusion reactions with obinutuzumab are the data. It isn't published, but it is often cited that hydrocortisone didn't seem to be as efficacious as methylprednisolone and dexamethasone in controlling the infusion reactions. And obviously, I think people get in the habit of using hydrocortisone, that they recognize this difference, and actually do put that into practice.

Thomas J. Kipps, MD, PhD: That's a very good point. I would not substitute dexamethasone for methylprednisolone for another reason, in terms of how much steroids you have on the gastric mucosa. So methylprednisolone is the preferred premedication regimen.
                                                                                                                                                                                                                                                                                                                
Transcript Edited for Clarity


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Transcripts:

William G. Wierda, MD, PhD:
Ofatumumab was approved based on its activity in patients who were fludarabine-refractory and Campath (alemtuzumab)-refractory, or patients who are fludarabine-refractory with bulky nodes. Now, there's more data with ofatumumab. I wonder if Alessandra could comment on what her thoughts are on where ofatumumab fits in our toolbox of treatments for patients with CLL and what her thoughts are in terms of tolerability of that agent.

Alessandra Ferrajoli, MD: In terms of the second question, it's the easiest one to answer. In terms of tolerability, there is a little bit more of an infusion reaction with ofatumumab with respect to rituximab. However, the majority of the patients can tolerate the infusion. In terms of where it fits in the treatment landscape, definitely there is an advantage in treating with the combination of chemoimmunotherapy with ofatumumab for patients that have a relapse after rituximab therapy. I don't know whether we have solid data to show that this monoclonal antibody is superior for patients that are naïve, that have not been exposed to any CD20 monoclonal antibody. So my answer is, I'm not sure.

Susan M. O’Brien, MD: I think just one point, and you alluded to this, is that if I was going to put the three anti-CD20s in an infusion-reaction spectrum, ofatumumab would be here with rituximab. And you mentioned it was a little bit greater. But, you know, it's not substantially worse. Obinutuzumab would be over here. I would say I don't use more caution when giving ofatumumab than I would rituximab, which I think everybody gives with impunity and without even thinking twice about the toxicity. But I wouldn't say that about obinutuzumab just yet.

Alessandra Ferrajoli, MD: And the same for, possibly, cytopenias, both neutropenia and thrombocytopenia?

Susan M. O’Brien, MD: Yes.

Alessandra Ferrajoli, MD: There are data with obinutuzumab causing very prolonged thrombocytopenia more than the other two monoclonal antibodies.

William G. Wierda, MD, PhD: And the first dose of obinutuzumab is a split dose, as a standard approach, which we don't do with the other two antibodies, and I think that also does speak to the infusion-related issues.

Susan M. O’Brien, MD: You can get an infusion reaction 10 minutes into the infusion, and you can split the dose down to what you want. And we saw this with rituximab. Remember, we did use to do a split dose on rituximab. Nobody does it any more. So I think it's just silliness.

Thomas J. Kipps, MD, PhD: Well, on the risk of being silly, I think it's a good idea. And so I disagree with Susan on that. I think setting out to give 100 mg of obinutuzumab is actually not a bad thing, because if they get past 100 mg and come back the next day, it’s a relatively easy infusion. But oftentimes if you set upon and have the bag filled with the entire amount of antibody, and the patient has a very bad infusion reaction that forces you to stop treatment, you have to then stop the therapy, and obviously you have to then potentially carry it over for the next day. It just makes it more complicated.

I think that these infusion reactions can be managed, and it really depends on your infusion nurses. My full credit is to them in terms of how they manage the patient: giving the drug slowly on the first infusion after having given some glucocorticoids and watching very carefully how the patient is doing. Slowing the infusion down or stopping it altogether makes a big difference. And that first day is a long day because we do stretch it out for some time. But I feel a lot more confident going forward to give it with 100 mg the first day and then the remainder the next day. If everything is done correctly, I think that I'd just prefer that.

Susan M. O’Brien, MD: But Tom, that's because the infusion center's close. You're the one who mentioned that patients have lives, too. They don't want to come back two days in a row.

Thomas J. Kipps, MD, PhD: Well, I think it's very hard. I agree with you, but some of the patients call obinutuzumab rituximab with an attitude, and I see that. And so I tell patients to anticipate this going into it, and they brace themselves. And I say, ‘You know, we have to give it slowly, the 100 mg that first day, and if we get past this, we will be able to give all the antibody in one infusion with the next round.”

And I think they can accept it going forward for the first couple of days, being close to the infusion center. It's not a bad idea because we've had some patients develop tumor lysis syndrome–type qualities even after the first infusion of 100 mg or so. So, having that follow-up day where the patient's required to come in, I welcome that so you can more closely monitor your patient's electrolytes and everything else with hydration. In terms of my practice, I feel that this is something I prefer to do.

Richard F. Furman, MD: One of the interesting features about the infusion reactions with obinutuzumab are the data. It isn't published, but it is often cited that hydrocortisone didn't seem to be as efficacious as methylprednisolone and dexamethasone in controlling the infusion reactions. And obviously, I think people get in the habit of using hydrocortisone, that they recognize this difference, and actually do put that into practice.

Thomas J. Kipps, MD, PhD: That's a very good point. I would not substitute dexamethasone for methylprednisolone for another reason, in terms of how much steroids you have on the gastric mucosa. So methylprednisolone is the preferred premedication regimen.
                                                                                                                                                                                                                                                                                                                
Transcript Edited for Clarity
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