Pediatric Blood Cancers: Building Better Outcomes Through Bold Science

In this episode of the Treating Together podcast, host Pallav Mehta, MD, medical oncologist at MD Anderson Cancer Center at Cooper University Health Care and medical director of Reimagine Care, speaks with E. Anders (Andy) Kolb, MD, president and chief executive officer of Blood Cancer United (formerly The Leukemia & Lymphoma Society; LLS). Together, they unpack the major forces shaping change in pediatric hematologic malignancies—from biology to treatment/care delivery and advocacy—and how they converge to rapidly translate research into practice.

Key Discussion Points

The conversation explores the momentum in pediatric blood cancer research and treatment, highlighting how genomics, clinical trials, and large-scale initiatives are reshaping care. Highlights include:

• Distinct Biology Driving Different Treatment Needs: Advances in genomic profiling reveal that pediatric leukemias are biologically distinct from adult disease, with more structural mutations (eg, translocations) rather than targetable point mutations—limiting applicability of many adult therapies.
• Barriers to Progress in Pediatric Myeloid Malignancies: Despite advances, progress in pediatric myeloid malignancies lags behind due to fewer actionable targets and limited drug development incentives.
• Clinical Trials as the Backbone of Care: Unlike adult oncology, trial participation is deeply embedded in pediatric care, with high enrollment rates driven by limited approved therapies, strong cooperative group infrastructure, and family motivation.
• Measuring Impact Beyond Survival: Beyond traditional end points like overall survival, the concept of life years saved highlights the long-term impact of curing children and informs research prioritization.
• Survivorship as a Research Driver: Long-term treatment effects (eg, infertility, organ damage) shape modern trial design, with increasing efforts to reduce toxicity and replace chemotherapy with targeted or immune-based therapies.
• Global Efforts Accelerating Progress: Initiatives like Blood Cancer United’s Dare to Dream are advancing research, access, and advocacy for high-risk pediatric patients.

Transcript

Mehta: Welcome to another episode of the Treating Together podcast from Targeted Oncology. I am Dr Pallav Mehta; I’m a medical oncologist specializing in breast cancer for the last 20 years. I am really privileged to be able to have a conversation with Dr Andy Kolb, and I will let Dr Kolb introduce himself.

Kolb: Yeah, hi, thank you. Thank you for having me. [I’m] Andy Kolb; I’m a pediatric hematologist/oncologist and practiced at Nemours Children’s Health for many years, as well as in New York at [Memorial] Sloan-Kettering and Montefiore. But for the past 3 years, I’ve served as the president and CEO of Blood Cancer United, previously known as The Leukemia & Lymphoma Society.

Mehta: Great. I'll tell you, I have a personal connection with the LLS because it was just about 15 years ago when we got a phone call from my sister; her daughter was having some bone pain, and the night before, a subconjunctival hemorrhage. And so I told them to go get a [complete blood count]. Her white blood cell count was 140,000 and began an odyssey of relapsed/refractory [acute lymphoblastic leukemia], mismatched allotransplant, etc… She's alive and well today. A [Children’s Oncology Group; COG] protocol that she was randomized to the intervention arm, I think, played a lot into it with high-dose methotrexate. So, the LLS was also really instrumental in helping the family.

Kolb: Glad to hear she’s doing well. That sounds like a pretty rough course. I started with a personal connection as well. My wife was diagnosed with lymphoma back in 2007, and that’s what got me involved at the time.

Mehta: Yeah, and I think we actually are from the same med school. You left right before I came in.

Kolb: Yeah, yeah.

Mehta: So obviously I’m an adult oncologist, and the world of pediatric hematology/oncology, from the outside, sometimes a layperson may look at that as very similar. I think we both know there’s a lot of differences. I remember one of my attendings a long time ago saying, “Children are not small adults.” And children kind of have a [certain] natural history and different physiologies at all different ages, so it’s a really complicated disease set. But as you said, you’ve been at the bedside, you’ve been a leader in oncology; you’ve been—what I saw in your CV—a real builder of programs, and now you’re in a national advocacy space. And so from your vantage point, in your career…and over the last 10 years, what have been the bigger changes in blood cancer? And we’ll get into more specific issues as we talk.

Kolb: Yeah. First of all, thank you for calling out the idea that that children are not little adults, and I think that as pediatricians, we've always known that intuitively. But what has changed really has been the genomics—understanding the genomics—but also understanding host factors. Kids have remarkable metabolism, drug metabolism, remarkable excretion. Setting aside the differences in how kids can process therapeutics and just focusing on the disease itself, we have learned a tremendous amount.

When I took over as the chair of the COG myeloid disease committee—you had mentioned COG before—I chaired the group that focused primarily on AML [acute myeloid leukemia] and CML [chronic myeloid leukemia] and myeloid malignancies. And AML is a disease that increases in incidence with age. So, the older you get, the more likely you are to develop myelodysplasia or AML. Most older adults have clonal hematopoiesis, whether they know it or not, there's evidence of it. So you know that the risk for AML accumulates with time. So then why does an infant get AML? Why does a 5-year-old, a 10-year-old, 18-year-old get AML? And we knew there had to be a reason for it. We didn't know what that reason was.

But when we were thinking about doing clinical trials and we're modifying the doses of cytarabine and daunorubicin and other anthracyclines, it didn't matter so much what those differences were because we have a bunch of tools in our toolbox, but they're all sledgehammers, right? We didn't have any precision tools in our toolbox with, 7, 8, 10 years ago when we started to understand the differences in mutations that children get and adults get in their leukemias. We started to see that children are, in fact, not “little adults.” Children are much more likely to have some of those catastrophic genomic events, the translocations, the large insertions and deletions driving their leukemia. And then in fact, they will get translocations that just don't exist in older adults, whereas an older adult may have 3, 4, 5, single-nucleotide mutations or smaller insertions and deletions that are targetable. IDH1, IDH2 mutations are common. FLT3 mutations are common in both children and adults. NPM1 mutations are common in adults. But these are all NRAS mutations. These are all differences in frequency and in incidence between children and adults. So, the therapies that are developed for older adults with AML where there's a market force, a business reason to develop those therapies, they're really not likely to work in children because they're targeting different mutations. The exceptions now are of course FLT3, but also, NPM1, KMT2A mutations that can now be targeted with menin inhibitors. So there are some exceptions, but for many years we were hoping that there would be some trickle-down phenomenon as drugs were developed for older adults. But as we understood the genomics, we realized that just wasn't going to be the case, and that has stalled, somewhat, progress for children. The mutational events that happen in kids, there aren't a lot of therapeutic options for them right now.

Mehta: That's interesting. So when you say targeted therapies, are these referring to monoclonals, small molecule…?

Kolb: Small molecule kinase primarily. There are some targeted monoclonals like gemtuzumab ozogamicin [Mylotarg] which targets CD33, but for the most part we're talking about the small molecules.

Mehta: Okay. So when you think about some of the therapies that you know, so CAR [chimeric antigen receptor] T-cell therapy clearly started in the pediatric space and then the bispecifics—do you think there's a reason why those might be more effective, or are they more effective in pediatric patients than adult patients?

Kolb: Yeah. So if you're thinking about where we have been successful in pediatrics in developing new therapies, [that is] in the acute lymphoid leukemias and in lymphomas. So the B-cell diseases as opposed to the myeloid diseases, we've been very successful in developing new therapies—CAR T-cells, bispecific antibodies, monoclonal antibodies, rituximab [Rituxan]. It's been around for more than a quarter of a century, and I think that in general, targeting B-cells has proven to be a little bit easier—a lot easier than targeting myeloid malignancies. But yes, I think I do think many of the major advances in the B-cell malignancies, whether it's the initial chemotherapies or these immunotherapies, started in kids. Kids were the first ones to show efficacy and real benefit. And that is in part due to the fact that kids can handle a lot. They don't come to clinical trials with as many comorbidities as older adults, so there is that. But I also think it is the culture of clinical trials as the standard of care in pediatrics. Children don't have access to as many approved therapies, so often access to these drugs is driven by clinical trial participation. And I would say that lastly, it's a rare event. It's a rare and catastrophic event for a family to think about a cancer and a child and that physician, that care team, that parent, and that child want to learn as much as they can about the malignancy so that the next family doesn't have to suffer the same.

Mehta: Yeah, I remember the story of Sidney Farber and the emperor of all maladies. I think it was 1947.

Since you mentioned clinical trials, we'll go into that space a little bit. In the adult oncology space, we're envious of the ability to accrue that the children's space has. As a parent—so I have 3 children, a 24-, 21-, and 17-year-old—and if I wasn't a physician, I would almost be more skeptical of clinical trials. And there's an obvious skepticism built in, I think, as people think about studies. I'm curious what your thoughts are around accrual. Is it simply because there aren't that many therapies? And how do those conversations go?

Kolb: In my 25 years of enrolling patients on clinical studies, it was rare that a family wouldn't want to participate. I think there are a couple reasons behind that. First of all, these aren't double-blind, placebo-controlled trials. If they're randomized, it's an open-label study, meaning you know exactly what you're getting. The standard arm is always the best standard of care that's out there. And then the experimental arm, it's the standard of care plus something or the standard of care minus something in the mind of trying to preserve toxicity.

We also have decades of experience through cooperative groups, starting with CCG, Children’s Cancer Group; Pediatric Oncology Group, or POG, then they merged to be the COG in 2000. We had decades of experience showing that these cooperative group clinical trials sequentially improve survival and sequentially improve outcomes. And in ALL, the survival has gotten to the point where the clinical trials are now taking stuff away; let's see if we can substitute cytotoxic chemotherapies with antibody-based chemotherapy that may have less long-term [adverse] effects, for example. So I think it's decades of experience that these trials are actually not just in the best interest of that patient, but the best interest of all patients.

But really, I think it comes down to the parents. The parents see that this diagnosis has turned their world upside down; their life otherwise has stopped to be at the bedside of their child. And if a clinical trial offers them the opportunity to learn something, potentially the opportunity to get access to a new therapy they may not otherwise have access to, and if it has the potential to help the next kid that's diagnosed, they're all in. And I think for adults that are enrolling, the calculation is probably somewhat different. You would know better than I do. I don't want to make any assumptions, but I think the calculation is a little bit different.

And then, lastly, in a pediatric practice, a pediatric hospital, as I said earlier, enrolling patients on clinical trials is the standard of care. The departments, the staffing, the funding in that world is created to do just that because we know that children who enroll in clinical trials have better outcomes than children who do not. So, clinical trials have become the standard; that’s just how we do it.

Mehta: You’ve created a default culture as it were. I think in adult oncology, there's still a lot of cultural shifts both on the patient side and the clinical side. Currently, I think the [participation] numbers are still hovering around 5% or so.

Kolb: I think there was one year in my job at Nemours where we enrolled something like 140% of children on clinical trials because the number of trials, that numerator was bigger than the denominator. You know, there would be a therapeutic study. There would be a biology study. There may be a psychosocial intervention study. So, it's just multiple different trials.

Mehta: Wow. It’s wonderful.

Kolb: Yeah, it was great.

Mehta: So you have the COG, which I assume is the main [cooperative group]. Is it the only cooperative group?

Kolb: The only NCI [National Cancer Institute]-funded cooperative group.

Mehta: And so, how do you handle the referral networks? We already have a difficult time getting, from a community center, a child who might be 100 miles from an NCI cancer center. Do you collaborate with community oncology and community centers differently or what sort of processes are put in place?

Kolb: The COG is part of the National Clinical Trials Network or NCTN. It's the only NCTN program dedicated to children, so it is the NCI’s pediatric cancer research arm. There are over 200 sites, 220 or so sites in the US that are COG members. And there are very few—I don't want to say none—private practices out there in pediatric oncology. These are usually affiliated with major academic centers because of the intensity of care that's needed, because of the coordination of care that is needed. And if you're a member of one of those academic centers, small, medium, or large, you are most likely a COG member institution. What that gives those centers is, you are part of COG through a single contract, so every trial is governed by that contract, and a single central IRB review. So, within days of the trial being active by COG, it can be activated at 220 centers across the country. It also means that centers have the ability to do just-in-time activation. They can keep their active trial portfolio relatively small, but if they have a rare disease that walks through the door for which there's a COG study, they can activate it relatively quickly. So it really is a wonderful model for how to do rare disease research.

I know that, when I was at Nemours Children's Health, which was a mid-to-large-sized program with multiple sites in Delaware Valley and Florida, we kept a pretty large portfolio of trials open because we were going to most likely see a patient at one of our sites. Smaller centers, like I said, could focus on ALL and neuroblastoma and brain tumors where their highest disease prevalence [was], but still have the ability to open up that rare disease trial when a child walks through the door. Were it not for those NCI-funded efficiencies—the central contracting, the IRB, the just-in-time activation—we would lose a lot of patients. A lot of rare diseases would fall through the cracks of logistics and funding. It has been a very, very effective way to learn.

Mehta: It's a tremendous infrastructure that has been built and every party seems to be working together towards a shared goal. When you're looking at clinical trials, I recently read—I don't know if it's a more recent shift or how you're measuring progress and measuring outcomes—in adult oncology, [it’s] obviously disease-free survival and overall survival. But I read about, I think it was life years…

Kolb: Yeah, life years saved.

Mehta: How do you look at end points, and…

Kolb: So it's not so much a clinical trial end point or it's an extrapolation from a clinical trial end point. It's really looking at event-free survival and overall survival. But to me, as from the standpoint of a pediatrician, it kind of levels the playing field. When we're trying to figure out how [to] allocate funding, if you just look at disease incidence, the NCI funding is going to favor diseases that are most common in adults—lung cancer, colon cancer, breast cancer, some of the leukemias, which is great. We need funding for all of those diseases, but pediatric cancers: 100 different types of cancer, each of them increasingly rare as you go down the list.

But life years saved, when we did this analysis, what we did is we would look at the US population every year from the Social Security Administration. Starting in the 1970s where we have SEER data, we would look at disease prevalence and survival mortality rates. And then you can subtract the mortality rate from the number of people that are alive and figure out how many life years were saved as survival improves. As mortality rates go down, how many years of life have been added? If we look at blood cancers, it's about 25 million years of life have been added since the 1940s because of innovation.

And it also puts into perspective how much a child contributes to that. Saving the life of a 2-year-old, curing cancer in a 2-year-old is 80 plus years of life that have been saved. In a 20-year-old, you're looking at maybe 50, 60 plus years of life that have been saved. So, that is, I think, a wonderful way to look at how we measure success and allocate resources. I also think it acknowledges our mission at Blood Cancer United, [which] is to cure blood cancer and improve the quality of life for all patients. Life years saved I think acknowledges a nuance in that mission, which is yes, cure is the goal, but it's not always possible. Patients who are diagnosed with chronic myelogenous leukemia, when I was in my fellowship, had less than a 20%, 25% chance of surviving today without improving the cure rate by that much. Now, patients with CML have a normal life expectancy. My wife has follicular lymphoma; she may never be cured of her disease, but she hopefully has a normal life expectancy. She tells me that the biggest threat to her quality of life isn't her cancer; it's her husband. So, that means we're doing something right.

Mehta: That's right, that's right. That's the case for a lot of us, I think. I really like that. It's the optimistic, hopeful approach to outcomes, looking at life years saved. I like the premise of that.

Kolb: It very quickly translates into birthdays and anniversaries and milestones and all of that. It's a great way to great way to think about it. And I think cure and overall survival, we tend to look at 2 5-year end points. This is extending that line to its end for any individual. And for a 2-year-old who is cured of their leukemia, we want them to live to 80. We don't want them to die of [adverse] effects in their 20s when they're cured. It's a very important, I think, focus for how we measure long- term success of our work.

Mehta: Right. And actually, that was exactly a good segue because I wanted to touch upon this issue of survivorship. Again, in adult oncology, it's still about following up for appointments and getting mammograms and eating healthy. But in pediatric cancer, the concept of survivorship…my niece was 13 at the time and already was post-puberty, so it was permanent menopause and so she's on hormones. Can you speak a little bit to, both programmatically and even from a trial standpoint, how survivorship is viewed?

Kolb: Yeah. So, I think in pediatrics, we've been very good, though there's always room for improvement at understanding the survivorship impact. Your niece is a great example to survive your cancer but be in menopause or be infertile or need for major joint replacements before you’re 30. Those are important; the trial’s done, the trial’s been published, the survival rate’s up on the board in some publications somewhere, but those kids continue to live on and deal with the effects of their treatment. So understanding those survivorship issues means that maybe [for] the next trial, we’ll reduce the dose of cyclophosphamide so that fertility can be preserved or will substitute cyclophosphamide for a bispecific antibody. That was the basis of the approval of blinatumomab [Blincyto] a couple of years ago, was that blinatumomab improved survival in relapsed patients, but it was also able to be substituted for cytotoxic chemotherapy in upfront patients. Blinatumomab is not easy to give, and it does have some short-term [adverse] effects, but those [adverse] effects will hopefully be washed out when the drug's gone. [Adverse] effects from cyclophosphamide, daunorubicin, and radiation—they are lifelong, and it does govern and guide our research strategy. It has to govern and guide our research strategy. Survivorship isn't just about describing what happened and what the effects are; survivorship is about figuring out what's the next question for the next trials.

Mehta: Right. Switching gears in the last couple of minutes that we have, I want to make sure I touch upon the Dare to Dream project. So we think of these sometimes just as a fundraising project, but I know it's a lot more in terms of operationally what's happening. If you can describe, what's actually changing for the child with leukemia and for the family?

Kolb: I'm glad you asked about Dare to Dream. I think this comes back to the start of the conversation where we were talking about the need to develop precision medicines for pediatric patients. Blood Cancer United recognized this need and committed to investing 175 million dollars into progress for some of the more refractory pediatric blood cancers—pediatric AML and relapsed ALL, for example. The backbone of Dare to Dream is a global master clinical trial that recognizes that to do some of these studies, especially in rare diseases, we really need patients from all around the world to be able to participate. The foundation of the trial in the US is a screening study that is run through COG through the NCI mechanism, but funded by Blood Cancer United, so a really great partnership between some of the leading consortia and support mechanisms in the United States. That has already enrolled and provided diagnostic and screening information for more than 600 pediatric patients around the country, and has sub-trials that are open on 4 different continents, testing novel new therapies for relapsed and refractory leukemias in children.

It's also about funding new research. So we have invested tens of millions of dollars in new research grants and new callouts for pediatric-specific investigations to help identify the foundations of pediatric blood cancer so that we can work on developing the next generation of therapies. And then there are patient support resources available, so clinical trial navigation and support for patients and families who have urgent, financial needs or who need travel support, funding, whatever it might be to get to clinical trials to get to CAR T-cell treatment. Lastly, we have an advocacy arm and we have been very active trying to advocate for national research funding for pediatric cancers, as well as policies that support access to affordable care. About half the kids in the United States who have cancer are supported all or in part by Medicaid and so shifts in Medicaid eligibility and funding at the state level or at the federal level can have a huge impact on patients’ ability to access care. So, that is Dare to Dream in a nutshell. It is a very ambitious program. But if we're going to continue to drive progress for children with blood cancers, we need something big and ambitious like this.

Mehta: I think ambitious was exactly the word I was thinking about. I mean, this is such an all-encompassing initiative. And, again, I think all aspects of health care could learn from the pediatric oncology teams that you're a part of. So, I really thank you for being here. There's so much to talk about. And I think both for families and for children, the progress has been remarkable because of people like you and teams that you lead.