Treatment Advancements Bring Optimism in Infant Leukemia

Recent advancements have brought optimism when it comes to treating infant patients with leukemia, particularly those with acute lymphoblastic leukemia, or ALL, as one expert explained in an interview with CURE.

CURE sat down with Dr. Tanja A. Gruber, Division Chief of Pediatric Hematology, Oncology, Stem Cell Transplantation & Regenerative Medicine at Stanford Medicine Children's Health.

Transcript

What are some current clinical trials that patients and their families should be aware of, particularly with regards to infant leukemia?

What we know from genetic studies on the tumor cells themselves is that the majority of these babies or infants have a very particular mutation that makes the leukemia cells resistant to standard chemo. We've actually been using a very standard chemotherapy regimen for the past 25 years, and we know that that treatment doesn't cure the majority of the infants.

So, what we did in my laboratory is we took samples. Patients' families were very generous and donated leftover leukemia cells from bone marrows that were done to diagnose the cancer. We took those cells and screened them with over 1,000 FDA-approved drugs to try and find drugs that were active against this leukemia that weren't being used. That was how we established the treatment regimen for the first study we conducted, called TINI, which stands for Total Therapy for Infants with ALL. We incorporated two drugs into the chemotherapy regimen that previously weren't being used. These drugs were being used for other types of cancers but not for infants with acute lymphoblastic leukemia. One of these drugs is a proteasome inhibitor called Velcade (bortezomib), and one drug is a histone deacetylase inhibitor called resminostat. What we found is that when we incorporated those medicines into the treatment, we were able to get a much lower disease burden.

After one cycle of chemo, we were able to get the leukemia down much better than with the standard chemotherapy that was being used for the first six weeks of treatment. We presented that at the American Society of Hematology meeting in December 2023, and the full paper is now under review, so we hope to publish it very soon. This now provides us with a more effective chemo on which to build from.

With this second trial, which is now open, we've activated at 10 sites across the U.S. and will have a total of 25 sites opening the study. The study builds on that chemo, and what we've done is we've added a type of immune-directed therapy called Blincyto (blinatumomab). What it does is it's an antibody, a molecule that recognizes the leukemia and then also brings one of the patient's own immune cells into proximity, and then the immune cell kills that leukemia cell. So, it's a type of immunotherapy, but it's not maybe as complex as CAR-T cell therapy because we have vials of it and can administer it to patients, and this drug has been shown to be very effective at improving outcomes for childhood acute lymphoblastic leukemia. What it's recognizing on the leukemia cells is a protein called CD19, which is also present on the infant acute lymphoblastic leukemia cells.

The other thing we're doing is there's a new drug which is very specific for leukemia cells that have that mutation that the infant leukemia patients have. We call that mutation a KMT2A rearrangement. Essentially, the drug is active against cells that have that KMT2A mutation but not against cells that don't. So what we're doing is we're incorporating this drug as well into the chemotherapy regimen for the babies. We're very excited. We've activated and are open to enrollment. We've already enrolled five patients, and we're very optimistic that this is going to improve the cure rates for these infants.

Transcript has been edited for clarity and conciseness.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.