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Practical Information on Immunotherapy Use

Panelists:Keith Stewart, MD, CHB, Mayo Clinic;William I. Bensinger, MD, Swedish Cancer Institute;Rafael Fonseca, MD, Mayo Clinic;C. Ola Landgren, MD, PhD, Memorial Sloan Kettering Cancer Center;Jatin P. Shah, MD, MD Anderson Cancer Center
Published Online: Wednesday, Aug 31, 2016



Transcript:

Keith Stewart, MD, CHB:
If you’re in a community, this is a drug that takes a whole day to infuse. Is it worth it?

C. Ola Landgren, MD, PhD: I think the practical implications are very important, and beyond the durations of the first dose is the dose when you have the infusion reactions. Probably in 30%, 40% of patients you see these reactions, and they’re allergic-type of reactions. But also importantly…

Keith Stewart, MD, CHB: What kind of reactions are they, for those who haven’t used it?

C. Ola Landgren, MD, PhD: You have, like, drops in blood pressure, tachycardia. You could have bleeding.

Keith Stewart, MD, CHB: Often upper respiratory.

C. Ola Landgren, MD, PhD: Upper respiratory, exactly. Patients who have asthma as a background history, they need to be on bronchodilators to prevent that from getting worse. I think other very important aspects: you need to make sure you do type and screen, if you need to give blood later, because the drug interferes with the workup you do in the blood bank. And also when you draw the blood for evaluation of the M-spike—because the drug is a monoclonal antibody—it’s going to show up as a band in the workup in the lab. So, if the patient has an IgG kappa M-spike, you now see the disease is more prominent because you could see the drug in the laboratory.

Keith Stewart, MD, CHB: I wondered about that because in the EHA abstract, which is all we’ve seen so far, the complete response rate was astonishingly high, and I wondered how they measured that then with the circulating antibody.

C. Ola Landgren, MD, PhD: I think they have done the reflex assays where they have had idiotypic antibodies that bound to the drug so they could migrate the bands, and then they could distinguish the drug from the disease. Those are not available. I think for the publications, the data is probably a little cleaner than in reality, so I caution that.

Keith Stewart, MD, CHB: And Rafael, you mentioned isatuximab is also an anti-CD30 antibody. It’s a little bit behind in its clinical development, but some data were presented on that yesterday here at the ASCO meeting.

Rafael Fonseca, MD: Yes, there’s a number of studies that are looking at isatuximab-based combination. And we have had the privilege of being involved in some of those sites with the leadership of Joe Mikhael. I think it’s very clear. It’s a highly active regimen; isatuximab is a highly active drug. But just like what we’re seeing with daratumumab, the rate of responses increases when it’s combined with other agents. And we’ve seen that with Tom Martin presenting some data with the lenalidomide/dexamethasone combinations, which really are fantastic. So, I would anticipate it’s just going to be right behind the heels of daratumumab and will provide another option. And, again, all this is temporary because now we’re going to start talking about new formulations, new routes of administrations that will hopefully circumvent some of the challenges with infusions.

Jatin P. Shah, MD: I think you asked a very nice question, which I think highlights something a little bit deeper—“Is it worth it?. And when you ask, “Is it worth it?” the conversation that we all have with our patients has always been around risks and benefits, right? Here are the risks, here are the benefits, here’s infusion reactions, and here’s this, right? And then, so you talk about the response rates, and the PFS, and the long-term survival, etc. I think that’s still the most important conversation to have with patients. And the reason I say that is because I think there’s been a change in that conversation where I may offer you a “would you like” question. As opposed to giving you the risks and benefits, I’m giving you a different conversation, which is subtly different, which is, “Would you like IV or oral therapy?” That does not go into the full depth of the oral because, potentially, the IV may be much better tolerated, a much more potent combination.

But if you phrase the conversation to the patient as, “Would you like all oral or would you like all IV?”, you’re not really getting to the depth of the conversation about the risks and benefits. And so I think that if you marginalize the rest of that by asking oral or IV, you’re missing some of that. I think it’s important, when we start talking about this, to make sure that as we look at these new therapies, to really focus on the risks and benefits, response rates, PFS, long-term survival, and not just, “Would you like oral or IV?”, and then have a conversation go from there. That’s just an important subtle point, which I think is important for our physicians.

Keith Stewart, MD, CHB: Before we close on treating relapsed disease, any differences in the elderly versus the younger patient here with approaches?

C. Ola Landgren, MD, PhD: I have given daratumumab to older people, and they seem to tolerate that very well. I think that’s one of the benefits with the monoclonal antibodies—that they seem to be very well tolerated.

Keith Stewart, MD, CHB: But elotuzumab in this setting, would you use daratumumab first, elotuzumab second; elotuzumab first, daratumumab second? Eugene says we should use them all at some point.

C. Ola Landgren, MD, PhD: Well, I think it comes back to the same question we talked about before. We don’t really know the right sequence, if it’s better to do them stepwise, or you do the more powerful up front. If you do them stepwise, I do think elotuzumab first and then you could go to daratumumab. But no one really knows which model is the right…

Keith Stewart, MD, CHB: Maybe you should use them together.

C. Ola Landgren, MD, PhD: Maybe that. We don’t know that. We don’t have the data. We don’t have head-to-head comparison. But for sure in clinical practice, I think for patients with an indolent relapse, there is nothing wrong using elotuzumab first and go to daratumumab later.

Transcript Edited for Clarity

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Transcript:

Keith Stewart, MD, CHB:
If you’re in a community, this is a drug that takes a whole day to infuse. Is it worth it?

C. Ola Landgren, MD, PhD: I think the practical implications are very important, and beyond the durations of the first dose is the dose when you have the infusion reactions. Probably in 30%, 40% of patients you see these reactions, and they’re allergic-type of reactions. But also importantly…

Keith Stewart, MD, CHB: What kind of reactions are they, for those who haven’t used it?

C. Ola Landgren, MD, PhD: You have, like, drops in blood pressure, tachycardia. You could have bleeding.

Keith Stewart, MD, CHB: Often upper respiratory.

C. Ola Landgren, MD, PhD: Upper respiratory, exactly. Patients who have asthma as a background history, they need to be on bronchodilators to prevent that from getting worse. I think other very important aspects: you need to make sure you do type and screen, if you need to give blood later, because the drug interferes with the workup you do in the blood bank. And also when you draw the blood for evaluation of the M-spike—because the drug is a monoclonal antibody—it’s going to show up as a band in the workup in the lab. So, if the patient has an IgG kappa M-spike, you now see the disease is more prominent because you could see the drug in the laboratory.

Keith Stewart, MD, CHB: I wondered about that because in the EHA abstract, which is all we’ve seen so far, the complete response rate was astonishingly high, and I wondered how they measured that then with the circulating antibody.

C. Ola Landgren, MD, PhD: I think they have done the reflex assays where they have had idiotypic antibodies that bound to the drug so they could migrate the bands, and then they could distinguish the drug from the disease. Those are not available. I think for the publications, the data is probably a little cleaner than in reality, so I caution that.

Keith Stewart, MD, CHB: And Rafael, you mentioned isatuximab is also an anti-CD30 antibody. It’s a little bit behind in its clinical development, but some data were presented on that yesterday here at the ASCO meeting.

Rafael Fonseca, MD: Yes, there’s a number of studies that are looking at isatuximab-based combination. And we have had the privilege of being involved in some of those sites with the leadership of Joe Mikhael. I think it’s very clear. It’s a highly active regimen; isatuximab is a highly active drug. But just like what we’re seeing with daratumumab, the rate of responses increases when it’s combined with other agents. And we’ve seen that with Tom Martin presenting some data with the lenalidomide/dexamethasone combinations, which really are fantastic. So, I would anticipate it’s just going to be right behind the heels of daratumumab and will provide another option. And, again, all this is temporary because now we’re going to start talking about new formulations, new routes of administrations that will hopefully circumvent some of the challenges with infusions.

Jatin P. Shah, MD: I think you asked a very nice question, which I think highlights something a little bit deeper—“Is it worth it?. And when you ask, “Is it worth it?” the conversation that we all have with our patients has always been around risks and benefits, right? Here are the risks, here are the benefits, here’s infusion reactions, and here’s this, right? And then, so you talk about the response rates, and the PFS, and the long-term survival, etc. I think that’s still the most important conversation to have with patients. And the reason I say that is because I think there’s been a change in that conversation where I may offer you a “would you like” question. As opposed to giving you the risks and benefits, I’m giving you a different conversation, which is subtly different, which is, “Would you like IV or oral therapy?” That does not go into the full depth of the oral because, potentially, the IV may be much better tolerated, a much more potent combination.

But if you phrase the conversation to the patient as, “Would you like all oral or would you like all IV?”, you’re not really getting to the depth of the conversation about the risks and benefits. And so I think that if you marginalize the rest of that by asking oral or IV, you’re missing some of that. I think it’s important, when we start talking about this, to make sure that as we look at these new therapies, to really focus on the risks and benefits, response rates, PFS, long-term survival, and not just, “Would you like oral or IV?”, and then have a conversation go from there. That’s just an important subtle point, which I think is important for our physicians.

Keith Stewart, MD, CHB: Before we close on treating relapsed disease, any differences in the elderly versus the younger patient here with approaches?

C. Ola Landgren, MD, PhD: I have given daratumumab to older people, and they seem to tolerate that very well. I think that’s one of the benefits with the monoclonal antibodies—that they seem to be very well tolerated.

Keith Stewart, MD, CHB: But elotuzumab in this setting, would you use daratumumab first, elotuzumab second; elotuzumab first, daratumumab second? Eugene says we should use them all at some point.

C. Ola Landgren, MD, PhD: Well, I think it comes back to the same question we talked about before. We don’t really know the right sequence, if it’s better to do them stepwise, or you do the more powerful up front. If you do them stepwise, I do think elotuzumab first and then you could go to daratumumab. But no one really knows which model is the right…

Keith Stewart, MD, CHB: Maybe you should use them together.

C. Ola Landgren, MD, PhD: Maybe that. We don’t know that. We don’t have the data. We don’t have head-to-head comparison. But for sure in clinical practice, I think for patients with an indolent relapse, there is nothing wrong using elotuzumab first and go to daratumumab later.

Transcript Edited for Clarity
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