Dr DeAngelo on Challenges With Utilizing Pediatric-Inspired Regimens in Adult and AYA ALL

"The big issue with the utilization of pediatric-inspired regimens is that they're difficult to adopt…in the community or in smaller academic centers. These are complicated regimens with complicated drugs. The other issue is that this is a rare disease, so it's going to be very hard to ever get a randomized study comparing adult, non-asparaginase–containing vs pediatric-inspired regimens. This prompted us to conduct a meta analysis."

Daniel DeAngelo, MD, PhD, a professor of medicine at Harvard Medical School and chief of the Division of Leukemia at Dana-Farber Cancer Institute, discussed the challenges of using pediatric-inspired, asparaginase-containing regimens compared with hyper-CVAD in adult and adolescent or young adult (AYA) patients with acute lymphoblastic leukemia (ALL), highlighting the rationale behind conducting a meta analysis regarding theses regimens.

Although pediatric-inspired regimens have demonstrated improved outcomes in AYA patients, their adoption remains limited, particularly outside of large academic centers, DeAngelo began. Prior findings have highlighted the underutilization of pediatric-inspired regimens in community-based or smaller academic practices within California, he said, adding that although academic centers were more likely to use these regimens, their broad, real-world use was sparse. This disparity largely reflects the complexity of pediatric-inspired protocols, which require near-weekly regimen modifications and involve intensive outpatient management, DeAngelo explained.

Asparaginase, a key component of these regimens, introduces additional clinical challenges in adult and AYA patients, especially those with elevated body mass index, DeAngelo stated. These include a heightened risk of thrombosis, hepatic toxicity, and pancreatitis, which complicate administration and monitoring, he detailed. These adverse effects, coupled with the need for meticulous outpatient compliance, have made the broader application of pediatric-inspired regimens logistically difficult, he underscored.

Moreover, adult ALL is a rare disease, making large-scale, randomized comparisons between pediatric-inspired regimens and standard adult regimens like hyper-CVAD infeasible, DeAngelo continued. This rarity has impeded efforts to generate definitive prospective comparative data, he said.

As a result, DeAngelo and colleagues designed a meta-analysis to explore the relative efficacy and safety of these approaches. Although such analyses have many limitations, they can provide valuable insights into the comparative effectiveness of pediatric-inspired regimens vs hyper-CVAD in adult and AYA ALL, helping inform practice patterns in the absence of randomized trial data, DeAngelo concluded.