A New Standard: Blinatumomab + Chemo in Childhood Acute Lymphoblastic Leukemia | Rachel Rau | #ASH24

Our study was a clinical trial that was conducted by an organization called the Children's Oncology Group, which is the world's largest cancer consortia for children. And this particular trial was focused on children with the most common type of cancer in childhood called B-cell acute laryngoplastic leukemia, or B-ALL. Our study specifically focused on children less than the age of 10 when they're diagnosed. That's the largest subset of patients who have B-ALL. And we wanted to ask the question if adding an immune-based therapy to our standard chemotherapy approach would improve outcomes. The immune-based therapy is called Blenotumab, and it works by binding to a molecule on the surface of the bad B-cells, the cancer cells, and then the other side attaches to the patient's own T-cells, which are a cell that helps fight off cancers. And so it engages the T-cells to kill the malignant B-cells, so it uses the patient's own immune system to attack the cancer. And what we found is that when we added Blenotumab to standard therapy, it significantly improved outcomes. We had 61% reduction in relapses for patients who got Blenotumab compared to standard of care. So we got these results in July, and the week later we posted a memo saying that because this result is so striking that we should change our practice right now. Starting then and there, pretty much every hospital in the country is already giving these patients Blenotumab into their therapy the way we did it on the trial, which is kind of mind-blowing to be a part of. And none of it would have been possible without the research that we did on this trial and, most importantly, the willingness of families and patients to participate in this research study really led to that result, that overnight changed practice for how we treat this disease. And we're already incorporating Blenotumab into most patients' therapy based on this result, so it's really exciting to be a part of. So Blenotumab is, again, pretty well tolerated. It doesn't have the same toxic effects that most of the chemotherapy drugs we use right now do, so it doesn't make your blood counts go really, really low like standard chemotherapy does. But it does have some specific unique toxicities. For one, it can cause something called cytokine release syndrome, and that just means that when it starts doing what it's supposed to do, it breaks down the cancer cells, which release substances into the body that causes fevers and things like that. So that we saw in less than 1% of patients having a severe reaction like that to the Blenotumab. So overall, I would say that's less than most of those reported in adults, but our study was just designed somewhat differently, so it's really hard to compare apples to apples. The other sort of toxicity that we know is unique to Blenotumab are neurologic effects, including seizures and sort of changes in how you can think and tremors and things like that. We also saw pretty low rates of those adverse events as well on our trial, but again, because we gave it to patients who had pretty really low amounts of leukemia in their body at the time we gave it, it's harder to compare to the adult trials who usually give it when there's a bit more disease around, and that can increase the risk of those toxicities. So overall, I would say what we saw was pretty much what we expected in terms of the rates of those complications. Luckily, they weren't very common, but they can be severe, so something for families to be aware of when their child is getting Blenotumab. So Blenotumab is available right now to be given by continuous IV infusion, 28 days at a time. That is incredibly burdensome. If you live in a very rural area where you don't have home health care services and you can't travel back and forth to the clinic, it may not be accessible to you. Or if your child can't go to daycare with Blenotumab infusing and you can't take off 28 days of work to stay with your child, you may not be able to access that medicine. And really, if not every patient who would benefit from Blenotumab has access to it, then what have we accomplished here? So some things that we can do to overcome that is improve formulations. One that can be given by a subcutaneous injection is already being studied and looks very promising. So that would mean you just come to clinic to get shots for Blenotumab. I think that would help. There are also other products out there that are very similar but are longer lasting in the body. So you could get a once a week injection of the medicine. So just come into clinic once a week instead of having something 28 days at a time is probably going to make it more feasible. And I think that's the way the field will move. The medication is good. The mechanism is right. We just have to come up with better ways to give the medicine. In our trial, the only group of patients that didn't qualify for this are ones that we knew did already really, really well with standard chemotherapy alone. So there's a subset of patients who with just our standard treatment already have outcomes of 97, 98% relapse free survival. And at the time we started this trial, Blenotumab was still considered an investigational agent. And so we didn't want to risk interrupting their already effective therapy to try this investigational agent. So right now we wouldn't give it to those patients because they're already doing really, really well with our standard treatment. But for all other patients with BALL, they should get Blenotumab added to their therapy. Eventually what we'd like to do is take that group of patients that are doing really, really well with standard chemotherapy and take out some of that chemotherapy and replace it with Blenotumab, which is better tolerated. So those are sort of the subsequent steps that we'd like to pursue. The most important thing to understand is, again, this would not have happened without a clinical trial being conducted. And so that took families' willingness to participate in research for us to achieve this. And they have a partnership with their physicians and their trust in the process and their commitment to moving the science forward, maybe not even for their own child, but for every child who's diagnosed in the future. And for that we're just immensely grateful, of course. This is step one of what I see as a multi-step process to really get rid of a lot of that chemotherapy that can make it super sick and replace it with Blenotumab, which is much better tolerated. So those are the next sets of trials and studies that we would like to do. So this is where the field is moving, I think, is let's get rid of some of the stuff that we know makes patients really, really sick and replace it with something that's better tolerated.