Dr Maese on Asparaginase-Based Regimens in Adult/Young Adult ALL

“Significant adverse effects [with asparaginase] for adult and young adult patients with ALL include hepatotoxicity, pancreatitis, and thrombosis. There are data [that indicate] that liver toxicity may be higher in these older patients compared with younger patients, although it may depend on body habitus and demographic factors such as ethnicity.”

Luke Maese, DO, an associate professor on the Clinical Track in the Division of Pediatric Hematology/Oncology at the University of Utah School of Medicine; director of the pediatric Leukemia/Lymphoma and pediatric Cancer Genetics programs; director of the Clinical Trial Research Enterprise and co-director of the Bone Marrow Failure Program at Primary Children’s Hospital; and a member of the Family Cancer Assessment Clinic and Schiffman lab at Huntsman Cancer Institute, discussed treatment considerations for the use of asparaginase-containing regimens for the treatment of adult and young adult patients with acute lymphoblastic leukemia (ALL).

Asparaginase is an important component of treatment protocols for pediatric patients with ALL and has been incorporated into treatment regimens for these patients since the 1970s, Maese began. However, there was hesitancy to adopt the agent in the young adult patient population due to adverse effects (AEs) such as allergic and infusion-related reactions, as well as hypersensitivity toxicities, he added. Although these AEs are not as frequently observed in adult and young adult patients, they are still of concern, he noted.

More common AEs in the adult and young adult patient population include hepatotoxicity, pancreatitis, and thrombosis, Maese emphasized. Although these toxicities are more common in this patient population, their instance and severity can depend on patient characteristics such as body habitus and ethnicity, he said.

Maese noted that investigators have largely been unable to identify which patients are at the highest risk of pancreatitis following treatment with asparaginase. This can be an AE of significance, especially in patients with ALL who often have other comorbidities.

Thrombosis, another commonly observed AE, can be largely well managed with available and novel agents, Maese said. However, hepatotoxicity and thrombosis still contribute to hesitancy surrounding the use of asparaginase in adult and young adult patients with ALL, he concluded.

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Luke Maese, DO, discusses treatment considerations for asparaginase-containing regimens in adult and young adult patients with ALL.

Dr Maese on the Use of Pediatric-Inspired Regimens in AYA and Adult ALL

“Adapting our new agents to pediatric-inspired protocols is something that's in the works, and I do think that there is an appetite out there to continue to investigate.”

Luke Maese, DO, an associate professor at the University of Utah School of Medicine; director of the Pediatric Leukemia/Lymphoma and Pediatric Cancer Genetics programs, director of the Clinical Trial Research Enterprise, and co-director of the Bone Marrow Failure program in the Division of Pediatric Hematology/Oncology at the University of Utah Primary Children’s Hospital; and a member of the Family Cancer Assessment Clinic at the University of Utah Huntsman Cancer Institute, discussed how the evolution of acute lymphoblastic leukemia (ALL) management may bring treatment protocols from the pediatric realm to adolescent and young adult (AYA) and adult patient populations. 

During the 1940s and 1950s, ALL began to garner significant attention within the scientific and medical communities, particularly as chemotherapy emerged as a novel therapeutic approach, Maese began. At that time, the primary focus was on pediatric patients, given that ALL predominantly affected children, he said. The historical emphasis on managing pediatric ALL led to the development of large, collaborative research networks—both nationally and internationally—forming a highly cooperative pediatric oncology community, he explained. These efforts prioritized ALL as a central area of study, given its status as the most common malignancy in children, he noted.

As a result of this early focus, pediatric-specific treatment protocols were established, Maese described. These protocols were tailored to a population with minimal baseline organ dysfunction and the ability to adhere closely to prescribed regimens, with parental oversight facilitating consistent treatment administration, according to Maese. Consequently, these pediatric regimens achieved remarkable success, and current cure rates for pediatric B-cell ALL now exceed 90%, he emphasized.

In contrast, AYA and adult patients historically received different therapeutic regimens compared with pediatric patients, Maese reported. Over time, there has been growing interest in evaluating whether pediatric-inspired treatment protocols could be effective and feasible in older populations, he stated. Since approximately the early 2000s, accumulating data have demonstrated that such regimens can offer clinical benefit in AYA and adult patients with ALL; however, applying these intensive regimens in older cohorts requires careful consideration of patient-specific factors, including age, comorbidities, and psychosocial readiness, he added. Treatment tolerability—both physical and psychological—must be evaluated, as adherence is essential to treatment success, and therapy discontinuation due to non-medical reasons must be avoided whenever possible, he explained.

Evidence continues to support the use of pediatric-inspired regimens in AYA patients, showing favorable outcomes, Maese emphasized. As new therapeutic agents emerge, integrating them into these established pediatric-style backbones remains an area of active investigation, he concluded.

Luke Maese, DO, discusses how the evolution of AYA and adult ALL management may be inspired by treatment protocols used in the pediatric population.

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.

 in February 2025, findings showed that AYA patients treated with pediatric-inspired regimens were approximately twice as likely to experience a complete response compared with patients treated with hyper-CVAD. Additionally, patients given pediatric-inspired regimens were 1.8x more likely to survive vs those given hyper-CVAD. DeAngelo and colleagues concluded that asparaginase-containing, pediatric-inspired regimens were associated with improved outcomes vs hyper-CVAD in the AYA population. 

Although pediatric-inspired regimens have been associated with improved outcomes in AYA patients, one challenge in the field is that their adoption has remained 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. 

Asparaginase, a key component of these regimens, can also introduce 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.

Daniel DeAngelo, MD, PhD, shares the rationale behind a meta analysis of asparaginase regimens vs hyper‐CVAD in adult and AYA patients with ALL. 

Navigating Pediatric-Inspired Regimens in Acute Lymphoblastic Leukemia | Supplements and Featured Publications

Dr Maese on Asparaginase-Based Regimens in Adult/Young Adult ALL

Dr Maese on the Use of Pediatric-Inspired Regimens in AYA and Adult ALL

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