February 2016, Vol. 5, No. 1
Another Study Shows Benefit with a Pediatric Regimen in Young Adults with ALLASH 2015, ASH Highlights
A pediatric regimen achieves superior outcomes compared with adult regimens in adolescents and young adults with acute lymphoblastic leukemia (ALL). Several studies have already shown this outcome, and a multicenter phase 2 study presented at the meeting adds further confirmatory evidence in support of this approach. The multicenter phase 2 trial enrolled patients with ALL aged 18 to 50 years, whereas other trials evaluating â€śpediatricâ€ť or â€śpediatric inspiredâ€ť regimens had an upper age limit of 30 or 40 years.
Three-year overall survival (OS) with the Dana-Farber pediatric ALL regimen was 75% and 3-year disease-free survival was 73% in this trial, which was better than expected. â€śThe take-home point from trials of pediatric regimens to date is that overall survival and disease-free survival are improved compared with historical controls treated on prior adult regimens,â€ť said lead author Daniel DeAngelo, MD, PhD, Dana-Farber Cancer Institute, Boston, MA.
â€śThe regimen is tolerable in young adults with ALL and represents a major therapeutic advance,â€ť he said.
Thus far, all the trials of pediatric regimens in younger adults with ALL have been phase 2 trials. DeAngelo said it is unlikely that a phase 3 trial will be conducted.
The Dana-Farber regimen used in this trial employed weekly pegylated asparaginase, which is thought to be safer and longer lasting than E coli asparaginase, which this group of investigators used in previous trials.
The study included 110 high-risk young adult ALL patients treated with induction therapy; patients who achieved remission went on to 30 weeks of consolidation and 2 years of maintenance therapy. They were treated with central nervous system prophylaxis consisting of intrathecal chemotherapy and radiation starting on day 1, high doses of asparaginase, and nonâ€“cross-resistant drugs with different side effect profiles that allow use of a number of drugs.
The dose of pegylated asparaginase was adjusted because of toxicity concerns during consolidation therapy; the interval between doses was lengthened to every 3 weeks for a total of 10 doses instead of 15. Prophylactic anticoagulation with low-molecular-weight heparin was used during treatment with asparaginase, which reduced the incidence of thrombosis, DeAngelo said.
Of the 110 patients accrued to the trial, 65 were on higher-dose pegylated asparaginase and 45 on the amended protocol. Median age was 32 years; 61% were male. Eighty percent had B-cell ALL and 20% had T-cell ALL.
The rate of complete remission was 89%; 21 patients went on to transplant. Three deaths occurred due to transplant-related complications.
Subgroup analysis showed that patients under age 30 had a 4-year OS of 80% to 85%, which was significantly better than the other age groups. Also, patients with T-cell ALL did particularly well on this protocol, with an OS of 80% and 70% for B-cell Philadelphia chromosomeâ€“negative ALL.
â€śA surprising finding was the association between poor OS based on body mass index. Underweight and normal weight patients did much better than obese patients,â€ť DeAngelo said.
Minimal residual disease (MRD)-negative patients had improved outcomes compared with MRD-positive patients, but no data were provided at press time.
Adjusting the dosing of pegylated asparaginase reduced the rate of grades 3 and 4 hyperbilirubinemia, ALT elevations, and risk of thrombosis. The investigators noted that pegylated asparaginase had greater toxicity in older adults as well as in those with high body mass index (>30). DeAngelo said that these patients have psychosocial needs that require attention. â€śWe need a unified approach to make progress in ALL, and this means more cooperative group trials in adolescents and young adults with ALL,â€ť he stated.
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