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VBCC - April 2016, Vol 7, No 3 - Hematologic Malignancies
Phoebe Starr

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 ASH 2015 adds further confirmatory evidence in support of this approach. The trial enrolled patients with ALL aged 18 to 50 years; other trials evaluating “pediatric” or “pediatric-inspired” regimens had an upper age limit of 30 or 40 years.

The 3-year overall survival (OS) with the Dana-Farber Cancer Institute pediatric ALL regimen was 75%, and the 3-year disease-free survival rate was 73%, which was better than expected.

“The 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,” said lead investigator Daniel J. DeAngelo, MD, PhD, Director, Clinical and Translational Research, Adult Leukemia Program, Dana-Farber Cancer Institute, Boston.

“The regimen is tolerable in young adults with ALL and represents a major therapeutic advance,” said Dr DeAngelo.

Thus far, all the trials of pediatric regimens in younger adults with ALL have been phase 2 trials. Dr DeAngelo said that it is unlikely that a phase 3 trial will be conducted.

The Dana-Farber regimen in this trial used weekly pegylated asparagin­ase (Oncaspar), which is thought to be safer and longer-lasting than Escherichia coli asparaginase (Elspar), which this group of investigators used in previous trials.

The study included 110 high-risk young adults with ALL who received treatment with induction therapy; the patients who achieved remission went on to 30 weeks of consolidation treatment and 2 years of maintenance therapy. They received prophylaxis consisting of intrathecal chemotherapy and radiation starting on day 1, high doses of asparaginase, and non–cross-resistant drugs with different side-effect profiles that allow the use of a number of drugs.

The dose of pegylated asparaginase was adjusted for toxicity during consolidation therapy, and the interval between the doses was lengthened to every 3 weeks, for a total of 10 doses instead of 15. Prophylactic anticoagulation was used during treatment with asparaginase, which reduced the incidence of thrombosis, Dr DeAngelo said.

Of the 110 patients accrued to the trial, 65 received higher-dose pegylated asparaginase and 45 received the amended protocol. Overall, the median patient age was 32 years, 80% of the patients had B-cell ALL, and 20% of the patients had T-cell ALL.

The rate of complete remission was 89%; 21 patients went on to transplant and, of those, 23 had a relapse; 3 deaths occurred as a result of transplant-related complications.

Subgroup analysis showed that in patients aged <30 years, 80% to 85% had a 4-year OS, which was significantly better than other age-groups. In addition, patients with T-cell ALL did particularly well with this protocol, with an 80% OS; the OS was 70% in patients with B-cell Philadelphia-negative ALL.

“A surprising finding was the association between poor OS based on body mass index,” said Dr DeAngelo. “Underweight and normal-weight patients did much better than obese patients.”

Minimal residual disease (MRD)-negative patients had improved outcomes compared with patients with MRD.

Adjusting the dosing of pegylated asparaginase reduced the rate of grades 3 or 4 hyperbilirubinemia, alanine aminotransferase elevations, and the risk for thrombosis. Pegylated asparaginase had greater toxicity in older adults and in those with a high body mass index.

Dr DeAngelo said that these patients have psychosocial needs that require attention. “We need a unified approach to make progress in ALL, and this means more cooperative group trials in adolescents and young adults with ALL,” he stated.

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Last modified: May 9, 2016
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