Pediatric regimens for ALL show promise in adults

Issue: November 25, 2016

There are several areas of research interest related to the management of young adults with acute lymphoblastic leukemia that stand to impact these patients’ prognosis, according to Ryan D. Cassaday, MD, of Fred Hutchinson Cancer Research Center, the University of Washington School of Medicine and the Seattle Cancer Care Alliance.

“One of the bigger questions right now is what the optimal chemotherapy regimen is,” Cassady said. “There has been a lot of movement recently toward incorporating pediatric regimens into the standard approach to the treatment of young adults.”

Ryan D. Cassaday

A recent analysis conducted in adults aged 18 to 50 years with Philadelphia chromosome-negative ALL (Ph-ALL) compared hematopoietic stem cell transplantation with a pediatric-inspired, non-HSCT regimen. The study included 422 adults who underwent HSCT and an age-matched cohort of 108 patients who received a Dana-Farber Consortium pediatric-inspired non-HSCT regimen.

No significant difference in relapse was observed between the HSCT arm and the chemotherapy arm (24% vs. 23%) at the 4-year follow-up point, although patients in the HSCT arm were more likely to experience treatment-related mortality (37% vs. 6%; P < .0001) and less likely to achieve 4-year DFS (40% vs. 71%; P < .0001). The majority (69%) of deaths among patients who received chemotherapy occurred as a result of relapse; in the HSCT arm, 28% of deaths occurred as a result of leukemic relapse and 70% were related to HSCT-related toxicities.

“Many believe that [the pediatric-inspired regimen] is a better approach to treatment than some of the historical adult regimens that we use,” Cassaday told HemOnc Today.

However, the hyper-CVAD regimen – which includes hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone – may be an exception.

“Some single-institution data from MD Anderson suggests it’s comparable, although one of the limitations of that study is that a lot of patients in the hyper-CVAD arm got rituximab,” he said. “We’ve since learned, from data presented at ASH last year, that rituximab can improve the outcome with pediatric regimens as well.”

More research is needed regarding role of biology, definition of ‘young adults’

The biology of ALL, and how that impacts treatment, is also generating “a lot of interest,” particularly in regard to Philadelphia chromosome-like ALL and the BCR-able-1-like gene signature, according to Cassaday. Research presented at the ASCO Annual Meeting demonstrated that tyrosine kinase inhibitors were effective in both Ph-positive and BCR-able–positive ALL.

A greater understanding of these subtypes of ALL may also “identify a particularly high risk subset of patients,” Cassaday told HemOnc Today.

“It seems like it’s more common in the young adult age group, so understanding who has this subtype of ALL, how we test for it, how we can use it therapeutically, is going to be really important,” he said.

However, one issue that remains unclear – and that stands to impact the use of pediatric-inspired regimens in this patient population as well as the ability to use the biology of ALL to influence treatment – is how to formally classify a patient as a young adult. Currently, the National Cancer Institute defines individuals aged 15 to 39 as adolescents and young adults.

“A lot of studies have looked at this question using an arbitrary cutoff in the 30 to 40 age range,” Cassaday said. “There are some studies suggesting you can give a lot of these pediatric-inspired regimens even into later years, maybe into the 50-year age range. Beyond that, some of the toxicities start to get really difficult to manage.”

Two recent trials examining the use of pediatric-inspired regimens in adult patients with ALL found that the approach is feasible. However, both studies revealed toxicities related to asparaginase that resulted in dose reductions.

“If we believe that pediatric-inspired regimens are better for young adults with ALL, if we continue to push that envelop, when do we start to see that benefit be outweighed by the toxicities associated with it? It’s another issue we’re wrestling with,” Cassaday said. – by Julia Ernst, MS

References:

Adolescents and young adults with cancer. Available at: http://www.cancer.gov/types/aya. Accessed August 25, 2016.

DeAngelo DJ, et al. Abstract 80. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Fathi AT, et al. Cancer. 2016;doi:10.1002/cncr.30037.

Maury S, et al. Abstract 1. Presented at: ASH Annual Meeting and Exposition; Dec. 5-8, 2015; Orlando, Fla.

Seftel M, et al. Am J Hematol. 2015;doi:10.1002/ajh.24285.

Stock W, et al. Abstract 796. Presented at: ASH Annual Meeting and Exhibition; Dec. 6-9, 2014; San Francisco.

Disclosures: Cassaday reports no relevant financial disclosures. Please see the full studies for a list of all researchers’ relevant financial disclosures.