Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511

Author:

Wetzler Meir1,Sanford Ben L.2,Kurtzberg Joanne3,DeOliveira Divino3,Frankel Stanley R.4,Powell Bayard L.5,Kolitz Jonathan E.6,Bloomfield Clara D.7,Larson Richard A.8

Affiliation:

1. Leukemia Section, Roswell Park Cancer Institute, Buffalo, NY;

2. Cancer and Leukemia Group B (CALGB) Biostatistics, Duke University Medical Center, Durham, NC;

3. Duke University Medical Center, Durham, NC;

4. Marlene and Stewart Greenebaum Cancer Center, University of Maryland Cancer Center, Baltimore;

5. Wake Forest University School of Medicine, Winston-Salem, NC;

6. North Shore University Hospital, Manhasset, NY;

7. Ohio State University Comprehensive Cancer Center, Columbus;

8. University of Chicago, IL

Abstract

Abstract CALGB 9511 used pegaspargase (PEG-ASP) in lieu of the native enzyme. The aim was to compare differences in overall survival (OS) and disease-free survival (DFS) between patients who did and did not achieve asparagine depletion, defined by enzyme levels greater than 0.03 U/mL plasma for 14 consecutive days after at least 1 of 4 planned PEG-ASP administrations. Samples were available from 85 eligible patients. On univariate analyses, the 22 patients who did not achieve asparagine depletion had inferior OS (P = .002; hazard ratio [HR] = 2.37; 95% CI = 1.38-4.09) and DFS (P = .012; HR = 2.21; 95% CI = 1.19-4.13). After adjusting for age, performance status, leukocyte count, and karyotype in a proportional hazards model, both the OS and DFS HRs decreased to 1.8 (P = .056; 95% CI = 1.0-3.2 and P = .084; 95% CI = 0.9-3.6, respectively). We conclude that effective asparagine depletion with PEG-ASP is feasible as part of an intensive multiagent therapeutic regimen in adult acute lymphoblastic leukemia and appears associated with improved outcomes.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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