Real-world performance of the CALGB 10403 regimen in young adults in the United States
Abstract: The Cancer and Leukemia Group B 10403 (C10403) trial prospectively demonstrated the safety and efficacy of administering an asparaginase-containing pediatric regimen for the treatment of adolescents and young adults (AYAs) with acute lymphoblastic leukemia. Since its implementation as stan...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-08-01
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| Series: | Blood Neoplasia |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950328025000469 |
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| author | Brandon DaSilva Alicia Darwin Amy Zhang Rutu D. Vyas Kathryn Russell Jason S. Gilbert Virginia Tan Susan Feldt Hannah Johnston Emily C. Liang Adam S. DuVall Michaela Liedtke Wendy Stock Ryan D. Cassaday Marc Schwartz Jessica T. Leonard Lori S. Muffly Marlise R. Luskin |
| author_facet | Brandon DaSilva Alicia Darwin Amy Zhang Rutu D. Vyas Kathryn Russell Jason S. Gilbert Virginia Tan Susan Feldt Hannah Johnston Emily C. Liang Adam S. DuVall Michaela Liedtke Wendy Stock Ryan D. Cassaday Marc Schwartz Jessica T. Leonard Lori S. Muffly Marlise R. Luskin |
| author_sort | Brandon DaSilva |
| collection | DOAJ |
| description | Abstract: The Cancer and Leukemia Group B 10403 (C10403) trial prospectively demonstrated the safety and efficacy of administering an asparaginase-containing pediatric regimen for the treatment of adolescents and young adults (AYAs) with acute lymphoblastic leukemia. Since its implementation as standard of care, it is unknown how the C10403 regimen performs beyond the clinical trial setting. To bridge this knowledge gap, we designed a multicenter retrospective cohort study to examine the safety, efficacy, and challenges of completing C10403 in the “real world.” From October 2012 through June 2020, a total of 139 patients began induction as per the C10403 regimen across 6 US academic cancer centers. The median age was 26 years (range, 17-39), 69% were male, 55% were non-Hispanic White, and 27% were Hispanic. Among them, 122 patients (88%) achieved complete remission or complete remission with incomplete count recovery (CR/CRi) with C10403, 48 (35%) completed maintenance therapy, and 47 (34%) changed postremission regimens while in CR/CRi. The 3-year event-free survival (EFS) was 66% (95% confidence interval [CI], 55-74), and the 3-year overall survival (OS) was 81% (95% CI, 74-87). Four deaths occurred while on C10403 treatment: 1 during induction; and 3 later in the treatment course. The most common grade 3 or 4 adverse events during induction included alanine aminotransferase elevation (22%) and sepsis (14%). B-cell immunophenotype (hazard ratio [HR], 2.45; 95% CI, 1.09-5.48), Philadelphia chromosome–like genetics (HR, 3.05; 95% CI, 1.25-7.44), and Hispanic ethnicity (HR, 2.00; 95% CI, 1.06-3.78) were associated with worse EFS in univariate analyses. Overall, these real-world results are comparable to those of the C10403 trial. Further improvements are needed to enhance outcomes and regimen tolerability in the AYA population. |
| format | Article |
| id | doaj-art-dfd7e7b3b4b0416485e10a4ad1a096e6 |
| institution | Matheson Library |
| issn | 2950-3280 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Blood Neoplasia |
| spelling | doaj-art-dfd7e7b3b4b0416485e10a4ad1a096e62025-08-01T04:45:33ZengElsevierBlood Neoplasia2950-32802025-08-0123100111Real-world performance of the CALGB 10403 regimen in young adults in the United StatesBrandon DaSilva0Alicia Darwin1Amy Zhang2Rutu D. Vyas3Kathryn Russell4Jason S. Gilbert5Virginia Tan6Susan Feldt7Hannah Johnston8Emily C. Liang9Adam S. DuVall10Michaela Liedtke11Wendy Stock12Ryan D. Cassaday13Marc Schwartz14Jessica T. Leonard15Lori S. Muffly16Marlise R. Luskin17Department of Medicine, Stanford University School of Medicine, Stanford, CA; Division of Hematology Oncology, Department of Medicine, Columbia University, New York, NYDepartment of Medicine, Stanford University School of Medicine, Stanford, CAQuantitative Sciences Unit, Stanford University School of Medicine, Stanford, CAClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WADivision of Hematology and Oncology, University of Washington School of Medicine, Seattle, WADepartment of Medicine, University of Colorado School of Medicine, Aurora, CODepartment of Medicine, Oregon Health & Science University, Portland, ORDepartment of Medicine, The University of Chicago, Chicago, ILSection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, ILClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Department of Medicine, University of Washington, Seattle, WASection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, ILDivision of Hematology, Stanford Cancer Center, Palo Alto, CASection of Hematology/Oncology, Department of Medicine, The University of Chicago, Chicago, ILClinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA; Division of Hematology and Oncology, University of Washington School of Medicine, Seattle, WADivision of Hematology, University of Colorado, Aurora, CODepartment of Hematology and Medical Oncology, Oregon Health & Science University, Portland, ORDivision of Blood and Marrow Transplantation & Cellular Therapy, Stanford University School of Medicine, Stanford, CADepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Correspondence: Marlise R. Luskin, Department of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Ave, Dana 2056, Boston, MA 02215;Abstract: The Cancer and Leukemia Group B 10403 (C10403) trial prospectively demonstrated the safety and efficacy of administering an asparaginase-containing pediatric regimen for the treatment of adolescents and young adults (AYAs) with acute lymphoblastic leukemia. Since its implementation as standard of care, it is unknown how the C10403 regimen performs beyond the clinical trial setting. To bridge this knowledge gap, we designed a multicenter retrospective cohort study to examine the safety, efficacy, and challenges of completing C10403 in the “real world.” From October 2012 through June 2020, a total of 139 patients began induction as per the C10403 regimen across 6 US academic cancer centers. The median age was 26 years (range, 17-39), 69% were male, 55% were non-Hispanic White, and 27% were Hispanic. Among them, 122 patients (88%) achieved complete remission or complete remission with incomplete count recovery (CR/CRi) with C10403, 48 (35%) completed maintenance therapy, and 47 (34%) changed postremission regimens while in CR/CRi. The 3-year event-free survival (EFS) was 66% (95% confidence interval [CI], 55-74), and the 3-year overall survival (OS) was 81% (95% CI, 74-87). Four deaths occurred while on C10403 treatment: 1 during induction; and 3 later in the treatment course. The most common grade 3 or 4 adverse events during induction included alanine aminotransferase elevation (22%) and sepsis (14%). B-cell immunophenotype (hazard ratio [HR], 2.45; 95% CI, 1.09-5.48), Philadelphia chromosome–like genetics (HR, 3.05; 95% CI, 1.25-7.44), and Hispanic ethnicity (HR, 2.00; 95% CI, 1.06-3.78) were associated with worse EFS in univariate analyses. Overall, these real-world results are comparable to those of the C10403 trial. Further improvements are needed to enhance outcomes and regimen tolerability in the AYA population.http://www.sciencedirect.com/science/article/pii/S2950328025000469 |
| spellingShingle | Brandon DaSilva Alicia Darwin Amy Zhang Rutu D. Vyas Kathryn Russell Jason S. Gilbert Virginia Tan Susan Feldt Hannah Johnston Emily C. Liang Adam S. DuVall Michaela Liedtke Wendy Stock Ryan D. Cassaday Marc Schwartz Jessica T. Leonard Lori S. Muffly Marlise R. Luskin Real-world performance of the CALGB 10403 regimen in young adults in the United States Blood Neoplasia |
| title | Real-world performance of the CALGB 10403 regimen in young adults in the United States |
| title_full | Real-world performance of the CALGB 10403 regimen in young adults in the United States |
| title_fullStr | Real-world performance of the CALGB 10403 regimen in young adults in the United States |
| title_full_unstemmed | Real-world performance of the CALGB 10403 regimen in young adults in the United States |
| title_short | Real-world performance of the CALGB 10403 regimen in young adults in the United States |
| title_sort | real world performance of the calgb 10403 regimen in young adults in the united states |
| url | http://www.sciencedirect.com/science/article/pii/S2950328025000469 |
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