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Relapsed/Refractory ALL: Inotuzumab Ozogamicin

Panelists:Ryan D. Cassaday, MD, University of Washington School of Medicine; Mark R. Litzow, MD, Mayo Clinic; Aaron C. Logan, MD, PhD, University of California San Francisco; Bijal D. Shah, MD, Anthony S. Stein, MD, Gehr Family Center for Leukemia Research
Published: Monday, Apr 02, 2018



Transcript: 

Mark R. Litzow, MD: Ryan, give us your perspectives on the use of inotuzumab in the relapsed/refractory setting.

Ryan D. Cassaday, MD: As I said before, I think, if you look at endpoints like complete remission, response rate, and these kinds of things, the iNNOVATE study published in the New England Journal of Medicine earlier this year showed pretty clearly that inotuzumab ozogamicin is a more effective therapy than the standard-of-care chemotherapy options it was compared against. Where it starts to get a little bit harder in my opinion, or a little bit less optimistic, is when you start to actually look at the survival outcomes for the patients who were treated on that study. It certainly looks better than chemotherapy, but there’s certainly a lot of room for improvement. The MD Anderson group is now starting to combine low-intensity chemotherapy, the so-called “mini hyper-CVD chemotherapy backbone,” with inotuzumab. They’ve presented some data, both in the relapsed/refractory and also the frontline settings, that are interesting.

The challenge is that there’s still a nontrivial amount of toxicity. They are seeing some evidence of VOD (veno-occlusive disease), even outside the context of allogeneic transplantation. So, it remains a little bit unclear to me. There are also some data that we talked about earlier about adding bosutinib for Ph-positive patients. A very small number of patients with Ph-positive ALL were treated in the iNNOVATE study. It’s approved for Ph-positive ALL. It’s in the NCCN guidelines, but it’s a fairly small proportion. I think it’s a useful drug.

It’s clearly an active drug. Its future is probably going to be, as we said before, in combinations. We may still need to do a little bit of work to figure out what those optimal combinations are, and I would generally agree with all the points stated before about the concerns about auto-hepatotoxicity. Unlike blinatumomab, where there may be a signal of some patients who can have durable responses if they achieve a really deep remission, I am not convinced yet that inotuzumab ozogamicin is something that I would use as a single agent without any further therapy with a realistic expectation that someone is going to stay in remission.

Aaron C. Logan, MD, PhD: One of my concerns is that many providers may reach for inotuzumab because it has some favorable features, such as the ease of administering the drugs once a week for days 1, 8, and 15 as compared with blinatumomab, which requires continuous infusion. I think we just need to urge our colleagues to really think about whether that drug is the right therapy for that patient and to really think about their prior liver toxicities and whether they have ongoing liver abnormalities, especially if they’re en route to a transplant. You don’t want to ruin that 1 opportunity they have for a cure, which right now is going to be that transplant. So really think about use of inotuzumab.

Bijal D. Shah, MD: Extending that observation, you should think critically about who are the patients who were on the trial: white blood cell counts of 10,000 or less, and at first or second relapse. It was a different population, so understand who they were studying to achieve the outcomes that they achieved.

Mark R. Litzow, MD: Inotuzumab is being brought to the frontline setting. The Alliance is leading an intergroup trial that will combine it with the C10403 regimen in a randomized fashion to see if it adds to that pediatric backbone. I’m leading a trial that’s adding blinatumomab in the up-front setting, E1910, so we’ll see where these agents fit into newly diagnosed disease treatment.

Transcript Edited for Clarity 

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Transcript: 

Mark R. Litzow, MD: Ryan, give us your perspectives on the use of inotuzumab in the relapsed/refractory setting.

Ryan D. Cassaday, MD: As I said before, I think, if you look at endpoints like complete remission, response rate, and these kinds of things, the iNNOVATE study published in the New England Journal of Medicine earlier this year showed pretty clearly that inotuzumab ozogamicin is a more effective therapy than the standard-of-care chemotherapy options it was compared against. Where it starts to get a little bit harder in my opinion, or a little bit less optimistic, is when you start to actually look at the survival outcomes for the patients who were treated on that study. It certainly looks better than chemotherapy, but there’s certainly a lot of room for improvement. The MD Anderson group is now starting to combine low-intensity chemotherapy, the so-called “mini hyper-CVD chemotherapy backbone,” with inotuzumab. They’ve presented some data, both in the relapsed/refractory and also the frontline settings, that are interesting.

The challenge is that there’s still a nontrivial amount of toxicity. They are seeing some evidence of VOD (veno-occlusive disease), even outside the context of allogeneic transplantation. So, it remains a little bit unclear to me. There are also some data that we talked about earlier about adding bosutinib for Ph-positive patients. A very small number of patients with Ph-positive ALL were treated in the iNNOVATE study. It’s approved for Ph-positive ALL. It’s in the NCCN guidelines, but it’s a fairly small proportion. I think it’s a useful drug.

It’s clearly an active drug. Its future is probably going to be, as we said before, in combinations. We may still need to do a little bit of work to figure out what those optimal combinations are, and I would generally agree with all the points stated before about the concerns about auto-hepatotoxicity. Unlike blinatumomab, where there may be a signal of some patients who can have durable responses if they achieve a really deep remission, I am not convinced yet that inotuzumab ozogamicin is something that I would use as a single agent without any further therapy with a realistic expectation that someone is going to stay in remission.

Aaron C. Logan, MD, PhD: One of my concerns is that many providers may reach for inotuzumab because it has some favorable features, such as the ease of administering the drugs once a week for days 1, 8, and 15 as compared with blinatumomab, which requires continuous infusion. I think we just need to urge our colleagues to really think about whether that drug is the right therapy for that patient and to really think about their prior liver toxicities and whether they have ongoing liver abnormalities, especially if they’re en route to a transplant. You don’t want to ruin that 1 opportunity they have for a cure, which right now is going to be that transplant. So really think about use of inotuzumab.

Bijal D. Shah, MD: Extending that observation, you should think critically about who are the patients who were on the trial: white blood cell counts of 10,000 or less, and at first or second relapse. It was a different population, so understand who they were studying to achieve the outcomes that they achieved.

Mark R. Litzow, MD: Inotuzumab is being brought to the frontline setting. The Alliance is leading an intergroup trial that will combine it with the C10403 regimen in a randomized fashion to see if it adds to that pediatric backbone. I’m leading a trial that’s adding blinatumomab in the up-front setting, E1910, so we’ll see where these agents fit into newly diagnosed disease treatment.

Transcript Edited for Clarity 
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