iwAL 2025 | The value and mission of the International Workshop on Acute Leukemias

Naval Daver:

Hello, my name is Naval Daver. I’m a faculty in the Department of Leukemia at the MD Anderson Cancer Center in Houston, Texas. I focus on acute myeloid leukemia and MDS research, and it’s a pleasure here to have with me two world experts in acute myeloid leukemia who have been key pioneers in developing the iwAL meeting. We have Dr Charlie Craddock, as well as Dr Marina Konopleva. Charlie and Marina, maybe just briefly introduce yourself, please. 

Charlie Craddock:

Yeah, it’s a great pleasure to join. I think iwAL is a really important advance and part of the infrastructure internationally for advancing treatment of AML. I’m a leukemia and transplant doctor. I’m committed to the accelerated delivery of trials of novel therapies in this disease, which until recently has had such a paucity of effective therapies. Over to Marina. 

Marina Konopleva:

Hey, Naval and Charlie. I’m Marina Konopleva. I’m a physician scientist. Right now, I’m at the Montefiore Einstein Cancer Center in Bronx, New York. I focus on AML and novel therapeutics, specifically on BCL2 targeting agents and other novel agents. And I agree with Charlie that iwAL has been instrumental for bringing novel therapies and discussing where we’re going next in AML. It brings together the group of both basic science researchers and translational researchers and clinicians. And it’s famous for its very rich discussions. Sometimes, you know, they go into longer discussions, and we also invite the FDA to some of these meetings. So I’ve been really enjoying iwAL and sort of shaping where we go next. 

Naval Daver:

Yeah, thank you, Charlie and Marina. I mean, yeah, I agree. I think, you know, through our efforts and many others who have been helping with the meeting, it’s kind of really become a platform for open discussion. I think that is one of the key highlights of the iwAL. We all go to many meetings and moderate and participate in meetings where there’s a lot of presentation, didactic, heavy scenario. And those are good as well and important, but I think this meeting is really becoming a platform for the clinical investigators, the clinicians, the basic scientists, as well as the FDA and pharma to kind of really engage in a discussion and future directions. And I think we saw a lot of that at the iwAL meeting this year in 2025, you know, a heavy discussion focused on what is probably the number one thing on the mind of a lot of our AML doctors is MRD. And this impacts, you know, how we treat patients in the frontline, how we modify their treatment, how we transplant, what we do post-transplant. And I think platforms such as iwAL really may help guide us, our trials, both U.S. and international, and also the FDA, who I know was also quite interested with a lot of the discussions and where the field is moving. So maybe Charlie, you know, asking you, what do you think we can do and, you know, maybe increase the impact of iwAL or leverage this meeting into something further? I know you’ve had some thoughts on that. We’d love to hear them. 

Charlie Craddock:

Yes, let’s put a patient’s hat on for the moment, Naval, at a time of such therapeutic promise. I think what patients across the world would want would be a forum whereby clinical trialists from, not just the US, but Europe, Australia, and other jurisdictions can meet together to really identify what the critical tractable trial questions are. And they’d like to do, they should do that really also in the context of regulators so that we can get regulatory advice about appropriate endpoints so that the trials that we do are capable of supporting registration or certainly approval of the agent. And I think also there’s an increasing recognition that, providing it’s framed within the right context, discussions with pharma are also really important. In many ways, our aims are coterminous. And that was one of the excellent features, I thought, of this year’s iwAL meeting. There was, as you and I sometimes refer to, Naval, genuinely a crucible of thought. People coming together, challenging each other from across the world, from different trial organizations, and a number of really key trial propositions were put forward, were tested, were thought about in a regulatory context, and I think have engaged also pharma as innovative strategies for approval. So I think that this is a really unique opportunity internationally for us to come together, think about collaboration, but also think through in 2025, what are the infrastructures that we’re going to need to accelerate not only trial delivery, but also increasingly important real world data. So I think it’s a very special meeting. I think it’s going to increasingly become more interactive with the key partners we’ve talked about and I’m hugely looking forward to next year’s meeting. 

Naval Daver:

Thank you, and Marina, from a translational and science perspective I know we used to have less and we’re trying to increase the prominence and presentation of those aspects. But I still think there’s, you know, the science talks and then the clinical talks. You know, what do you think are other things we can do and kind of missions that iwAL could take on to kind of increase that engagement between the translational and basic science and the clinical? 

Marina Konopleva:

Yeah I think I personally believe that bringing in translational and basic science researchers will definitely enrich this meeting and give it a new perspective. But for example, this year we had a very productive session on immune therapies and we all know that in the AML field we haven’t made as much progress as in the other diseases such as ALL or lymphoma or myeloma even. But I think the discussion of why that was the case, what are the challenges and what are the new frontiers, right? After the CAR-T’s have not been working, after the bispecifics, we don’t have yet a single one approved. But now, you know, NK cells that have been in trials didn’t really make it. But now we have a new, perhaps like NK engagers, new types of NK cells that are armored with cytokines and can survive longer. So that I think we all believe that we will find a way of immunotherapy that will make like progress in this disease, but that’s been challenging. And I think bringing together the experts in the field who can attest to the novel developments in the field, such as Jeff Miller, John DiPersio, Marion Subklewe, and others, and together with the clinicians who have gone through some of these clinical trials and, you know, have evidenced their failure and maybe understand clinical aspects of that, I think that’s critically important for our kind of next step because I feel that, you know, immune therapy should still be our goal for some of the notoriously difficult diseases that we’re trying to cure, like p53-mutated disease or inversion 3 AML. So it’s just one example of what we have done this year and I was personally very impressed by the talks there and I was encouraged that we will find a new frontier in immunotherapy. 

Naval Daver:

Yeah I think that’s yeah I think you know, we discussed MRD quite a bit, and I think there’s definitely future directions there, and even to support early approvals and interventions, immunotherapy, as you mentioned. And I also particularly liked some of the talks, such as Charlie’s talk on the ACT platform and how we can administratively, as well as regulatory wise, kind of improve delivery of trials. You know, many of us spend 70-80 percent of our time on designing and operationalizing and analyzing clinical trials. And I think that there is a lot of slack in the system and inefficiencies. And I think those talks, as well as talks by the FDA, you know, kind of helping us understand what is needed at a regulatory level, because I’ve seen it so many times that what we think may be very promising or what we think may be sufficient data may not be. And I think it’s good for us and the pharma investigators to know early on that what is the expectation? What is the bar? What is the reason for having these particular endpoints as approval? So it helps save many years and lots of money as we design trials. So I think, you know, we want to continue developing the iwAL in the same spirit. It’s not going to be a meeting that is heavily didactic focused. It is kind of made by the experts, but for also experts and regulatory and pharma. And as Charlie mentioned, I think we’re all looking forward to next year’s edition. Any final thoughts from Marina and Charlie? 

Charlie Craddock:

After you, Marina. 

Marina Konopleva:

Okay. I think I would like to highlight, going back to science, one more talk that I was really impressed by is on the cell-free DNA measurements of MRD. You know, I think we had a long session on the MRD regulatory endpoints, but then, you know, we had this presentation of Dr Tian Yi from Stanford who developed this novel assay that can measure minimal residual disease in the plasma. And, you know, of course, that’s been done in solid tumors for a long time, but we haven’t had yet this coming to our clinics. And I think everybody was very excited about that, and everybody was kind of trying to see how we can develop that. What would it take for us to bring that to clinic? Like funding or patients samples and I think that iwAL will facilitate eventually this translation much faster. I think that’s kind of thing from the translational standpoint I would love to see like more and more on the iwAL and I’m sure that in the next meeting we’ll kind of see continuation of that topic and the novel approaches coming up. 

Charlie Craddock:

Yeah, I echo that. I think if we’re putting patients and improving patient outcomes at the heart of what we do. The Greek philosopher Heraclitus, when he said, nothing is permanent but change, these words should ring in our ears. We’re seeing remarkable advances in fundamental and applied science. We’re seeing at last really exciting new therapies, whether they’re drugs or immunotherapy. But we also need to be thinking, how do we work together, as you outlined, Naval, in a regulatory context with pharma who are making these agents, but with big clinical trial groups identifying synergies. So they accelerate the delivery of practice-changing data. And to do that, you need forums such as iwAL, where it’s a trusted space, investigators who are active trialists with scientists, with regulators, with pharma companies. And I actually think this is an idea whose time has come and is particularly suited for the therapeutic ferment that we have in 2025. And if I was a patient, and I think the patients I’ll see in clinic, if I was to describe to them what iwAL is aiming to do and the spirit of the discussions and the content and the excitement, I think my patients would really be delighted that this initiative is happening and has got so much support from across the community. 

Naval Daver:

Yeah, thank you. Really well said, Charlie and Marina. And then I do think, you know, at some point we do want to leverage iwAL more and to help shape trial design and objectively run trials. I think one of the things you mentioned, Charlie, is really critical. I think we’re at a critical juncture here where maybe the long five to seven year phase three trials are going to be very difficult to conduct because there are so many effective new drugs. The science is moving quickly. New therapies, targets, immune agents are coming. And we have to find better, more efficient and optimal ways to identify strong signals and move these drugs forward to get to our patients across the globe quickly without being locked in long, prolonged trials. And I think here, the international community, you know, whether it’s one country or two countries or major sites working together to deliver such data is going to be really, really critical. I think there has to be a change in our trial delivery system as well as endpoints, and I think everything is primed for that to happen and hopefully iwAL can be one of the spearheads to push that forward. 

Charlies Craddock:

Perhaps we should also just say a big thank you to VJHemOnc who had the vision, Charlie Grieve, to see how important creating such an arena would be for the community and his vision really, I think, has been vindicated. 

Marina Konopleva:

Absolutely. I totally agree. 

Naval Daver:

I think this has been a great initiative, not just iwAL, I know there are similar meetings happening in MDS and CLL and others, and really is one of the few platforms which is truly trying to be at least global. Many other meetings tend to have a US or European flavor. I think the efforts and hopefully will continue is to keep this truly global. So I think with that, thank you. And thank you to the VJHemOnc team and Charlie Grieve. And for those who are listening, hopefully if you have not joined, we hope you will be able to join us for one of the future iwAL meetings. And thank you all very much.

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