Promising Immunotherapy Approaches in AML

Transcript:

Harry Erba, MD, PhD: Let me close with just a few comments from you, Jorge. Your institution has been very active in looking at these checkpoint inhibitors and combinations in AML. Does this have legs?

Jorge E. Cortes, MD: We certainly have very high hopes for that because I think there is potential for immune approaches in AML. We think that there may be something there. So, we’ve been looking at many different ways of using these checkpoint inhibitors. We have more experience with nivolumab; that’s where we started. There are a few studies that have been presented here. One is in combination with azacitidine: first in the relapsed/refractory setting; then in the newly diagnosed, older patients; and then in the more intensive standard combination, cytarabine and idarubicin.

They’re single-arm studies, and certainly we’ve shown the safety, although you do see the toxicities that you would expect: pneumonitis and nephritis and all these things. We have good responses, and we have some comparisons with historical data that make us believe there is possibly some improvement. It certainly doesn’t look like it’s a dramatic shift in the curves. There are some trends, and these are historic controls. So, we have to take those results with caution, but there may be something there.

We also have a maintenance study that we showed at EAHAD (the European Association for Hemophilia and Allied Disorders) that suggested these high-risk patients who are relapsed are maybe maintaining responses longer. I think we still have a way to go to understand which inhibitor to use, how to combine them, and what the best setting is. Is it at the beginning, when they’re in remission? There’s a lot to learn. I have the bias to think that they will find a way into leukemia, but I don’t think we’re there yet.

Harry Erba, MD, PhD: I think there are lot of other immune-based approaches that we’re taking past immunity. We’re not done with antibody—drug conjugates. With the approval of gemtuzumab, I think there is hope that we can improve on that and improve the outcome for our patients. The bispecific T-cell engagers and the DARTs (dual-affinity retargeting agents) will engage the patient’s own immune system. And then, of course, there are CAR T cells, which is a panel discussion of all its own. So, I think we better not touch that one. I think this has been extremely informative. Before we end this discussion, I’d like to get closing thoughts from each of our panelists. Let’s start with you, Jorge.

Jorge E. Cortes, MD: I think AML has gotten a lot more exciting from the point of view of the knowledge and the activity and the research, etc. But importantly, it is much more hopeful for our patients because we are starting to see some improvement in outcomes in areas where we had not before. There is a lot of room to grow and to improve. We’re not done in any of the areas of drugs where we have approvals. And of course, there are many areas that are still uncovered. I think it emphasizes the importance of characterizing our patients well so that we can apply these drugs when they’re applicable in individual patients, use them wisely, and know where we have good data and where there are no indications, etc. And of course, we must continue enrolling patients in clinical trials because that’s what has led us to these approvals. There are many more tools and many more drugs in the development. If we do it well, I think in a few years, the landscape and the outcomes for our patients are going to be dramatically better.

Harry Erba, MD, PhD: Sasha?

Alexander E. Perl, MD: I think we spent many, many, many years arguing about things like how much daunorubicin we need to give to patients, and we’re not talking about that anymore because we’ve got better things to talk about. We’ve come to a point where the questions we have to answer have to do with, how do we take this new and exciting drug and make it work the best? How do we find as many drugs for as many patients? They’re there. There really are some really exciting avenues. This has been a great year in drug development for AML, and I can only hope that 2018 will be the same. With all the drugs on the landscape, whether it’s immunotherapeutics, new FLT3 inhibitors, IDH1 inhibitors, or a number of drugs that are coming down the pike—these could be at our fingertips very soon, drugs that we hope will become approved in the near future. It’s a great time to be in the AML docket.

Harry Erba, MD, PhD: Yes, but you don’t really know the right dose of daunorubicin still, do you?

Alexander E. Perl, MD: Of course. Now we can argue about the right dose of Mylotarg (gemtuzumab ozogamicin) and be confused about that. We didn’t have time for that.

Harry Erba, MD, PhD: Eunice?

Eunice Wang, MD: I’m also incredibly encouraged. I hate to use this stock term, but I think we are moving toward a truly personalized approach to AML in individual patients. I think that we have struggled with the complexity and the heterogeneity, both of our patients and the biology of the disease, for many years. We’re finally beginning to crack that.

I think the most exciting thing is not only these novel drugs targeting immunotherapy and microenvironment coming down the pike, but I also see now that we have known active agents, and a lot of the discussion that I’ve seen at this conference is how to combine them. We have one agent, this agent, and this agent. Why don’t we combine 3 agents? Why don’t we take an IDH inhibitor and a BCL2 inhibitor and Mylotarg? Why don’t we take liposomal 7-and-3 chemotherapy and add an FLT3 inhibitor? I think the real fun is going to be, as in myeloma, figuring out the myriad of combinations that could be possible over the next few years and seeing which one is really going to be the best. I’m excited to see that we actually have active agents we can play with, layering them together, and really looking at the patient, looking at the disease, and figuring out which thing to take from each category to make that patient live the longest.

Harry Erba, MD, PhD: You guys have taken all the thoughts I had, so I’m done. I think we should leave it at that. Thank you for all your contributions to this discussion. On behalf of our panel, we thank you for joining us, and we hope you found this OncLive^® Peer Exchange^® to be useful and informative. Thank you.

Transcript Edited for Clarity