SAN FRANCISCO– Teens and young adults don’t like being treated like children, but they should make an exception when it comes to acute lymphoblastic leukemia therapy, because pediatric ALL regimens are associated with significantly better event-free and overall survival among patients with ALL from the ages of 16 to 40 years.
Those findings come from a clinical trial 14 years in the making, in which 296 adolescents and young adults (AYA) with ALL were treated with an intensive pediatric chemotherapy combination regiment rather than a less-intensive adult regimen. At 2-year follow-up, the rate of overall survival (OS) was 78%, with the median overall survival not yet reached, and the event-free survival (EFS) rate was 66%, reported Dr. Wendy Stock from the University of Chicago Medical Center.
Dr. Wendy Stock
In contrast, EFS rates among AYA treated with adult regimens have historically ranged from 35-40%, Dr. Stock said at a press briefing at the annual meeting of the American Society of Hematology.
“These data really started 14 years ago at this ASH meeting when we presented data showing that young adults ages 16 to 20 who were treated on adult cooperative group studies in the United States fared much worse than the same age group who were treated on pediatric studies,” she said.
In 2008, Dr. Stock and her colleagues published a study (Blood 2008;112:1646-54) showing that AYAs treated under Children’s Cancer Group (CCG) protocols had an overall survival rate at 7 years of 67% and an EFS rate of 63%. In contrast, AYAs treated under Cancer and Leukemia Group B (CALGB) protocols had an OS of 46% and EFS of only 34%. The risk for worse outcomes was approximately twofold among adolescents treated with adult regimens, compared with those treated with pediatric regimens. The findings were similar in studies from France, the United Kingdom, and the Netherlands, Dr. Stock noted.
The investigators determined at that time that, under the CCG regimens, the teen and young adult patients received earlier and more intensive central nervous system prophylaxis and higher doses of nonmyelosuppressive drugs, especially glucocorticoids, vincristine, and pegylated asparignase, while those on the CALGB regimens received higher doses of myelosuppressive agents such as anthracyclines.
Because their original findings came from a retrospective study, the investigators decided to launch a prospective study,US Intergroup trial C10403, designed to evaluate outcomes among patients with ALL from the ages of 16-40 years when they were treated with a pediatric regimen by adult hematologists/oncologists in the cooperative group setting.
A total of 296 eligible patients with a median age of 25 years were enrolled. The patients had newly diagnosed ALL of T-cell or B-cell lineage; patients with Burkitt’s type ALL or ALL positive for the Philadelphia chromosome were excluded. The patients were treated with a regimen identical to the Capizzi methotrexate arm of the Children’s Oncology Group AALL0232 study. The regimen consisted of four intensive courses: remission induction, remission consolidation, interim maintenance and delayed intensification, and prolonged maintenance therapy. Patients who had an M2 marrow response after remission induction (more than 5% but less than 25% lymphoblasts) received an extended remission induction course of therapy.
As noted before, the EFS rate was 66% and the median EFS duration was 59 months. The 2-year overall survival rate was 79%. EFS rates were similar between patients with B-cell lineage (65%) and T-cell lineage (68%) ALL, and there were no significant differences in EFS or OS by sex or by age.
There were five (2%) treatment-related deaths during protocol therapy, including two cases of liver failure, both occurring during induction; two infections (one in the induction phase and one in the consolidation phase); and one ventricular arrhythmia (during induction). Treatment toxicities in general were similar to those seen in the standard therapy of the COG AALL0232 trial, although patients in the current study had an increase in risk for thrombosis and early hyperbilirubinemia.
“Our outcomes are similar to other prospective international studies which apply pediatric regimens to the young adult population of acute lymphoblastic leukemia,” Dr. Stock said.
In analyses of biological factors that affect outcome, the investigators found that white blood cell counts above 30,000/uL were associated with worse EFS and OS, and that the presence of a BCR-ABL1-like signature and overexpression of the gene CRLF2 were common and associated with significantly worse survival.
The investigators plan to use the study as a basis for future studies incorporating target antibodies and kinase inhibitors in an attempt to improve survival further by eradicating minimal residual disease, Dr. Stock said.