SAN FRANCISCO—About 35% of standard risk B-acute lymphocytic leukemia (B-ALL) patients meet low risk criteria and are almost sure to be cured using low intensity induction with vincristine, dexamethassone, peg-asparaginase, and intrathecal methotrexate, and post-induction therapy without intensive consolidation or high dose methotrexate, the Children’s Oncology Group (COG) AALL0331 study (Abstract 793) presented at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition has shown.
For the study, 5,377 patients with standard risk ALL were enrolled between 2005 and 2010. “This is the largest study to date in these patients,” said Leonard A. Mattano Jr., MD, from HARP Pharma Consulting in Mystic, CT, while presenting at the meeting. All patients received standard induction with vincristine, dexamethasone, peg-asparaginase, and intrathecal methotrexate.
Then, 1,857 patients who met standard risk-low criteria were randomly assigned to receive either a low risk standard (LRS) regimen or a low risk asparaginase (LRA) regimen. All patients received consolidation with mercaptopurine, vincristine, and intrathecal methotrexate and interim maintenance with dexmaethasone, mercaptopurine, oral methotrexate, and intrathecal methotrexate.
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Patients assigned to the low-risk asparaginase group also received peg-asparaginase during consolidation and interim maintenance phases. All patients also received identical subsequent delayed intensification and maintenance regimens. In 2008, the interim maintenance phase was changed to escalating doses of intravenous methotrexate in both treatment arms.
Results showed that the 5-year continuous complete remission and overall survival rates for standard risk-low patients were 96.4% and 98.8%, per the most current COG minimal residual disease definitions for low risk ALL. In addition, the 3-year event free survival was improved with intravenous methotrexate, but not statistically significant (P=0.16).
Intensification with peg-asparaginase was not found to significantly improve outcome as the 5-year continuous complete remission for LRA was 96.0% versus 94.4% for LRS (P=0.1), and the 5-year overall survival rates were 98.3% and 99.3% for LRA and LRS, respectively. No significant improvement with peg-asparaginase intensification was observed with either the oral or intravenous methotrexate.
Treatment-related adverse events were more common with peg-asparaginase intensification, but were overall uncommon. Dr. Mattano noted that there was a higher incidence of pancreatitis, thromboembolic events, osteonecrosis, anaphylaxis, febrile neutropenia, and infection in the peg-asparaginase group
“On this particular trial, pegasparaginase intensification does not significantly improve outcome, with a P value of 0.19,” Dr. Mattano concluded. By using an approach that lacks intensive consolidation and high-dose methotrexate, the cumulative doses of antracyclines and alkylating agents can be limited.
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