Comparison of CALGB 10403 (Alliance) and COG AALL0232 toxicity results in young adults with acute lymphoblastic leukemia

Abstract

Adolescents and young adults (AYAs) with acute lymphoblastic leukemia have improved outcomes when treated with pediatric-inspired regimens. CALGB 10403 was the largest prospective study to evaluate the feasibility of using a pediatric regimen in AYAs with acute lymphoblastic leukemia up to 40 years of age. This article presents the toxicity events observed in the CALGB 10403 study and compares these toxicities vs those observed among AYAs treated on the same arm of the companion Children's Oncology Group (COG) AALL0232 study. Toxicities in CALGB 10403 were similar to those observed in COG AALL0232. Some grade 3 to 4 adverse events were more often reported in CALGB 10403 compared with COG AALL0232 (hyperglycemia, hyperbilirubinemia, transaminase elevation, and febrile neutropenia). Adverse events correlated with body mass index ≥30 kg/m2 and some with increasing age. The mortality rate in CALGB 10403 was low (4%) and similar to that in the COG AALL0232 trial. A caveat to this analysis is that only 39% of CALGB 10403 patients completed all planned protocol treatment. In COG AALL0232, although 74% of patients aged <18 years completed treatment, only 57% of patients aged ≥18 years completed treatment. This scenario suggests that issues associated with age and treating physician may be a factor. Due to its improved survival rates compared with historical controls, the CALGB 10403 regimen is now a standard of care. The hope is that the rate of protocol completion will increase as more familiarity is gained with this regimen. These trials were registered at www.clinicaltrials.gov as #NCT00558519 (CALGB 10403) and #NCT00075725 (COG AALL0232).

Conflict of interest statement

Conflict-of-interest disclosure: D.C. has received research support for clinical studies conducted by the following organizations: Daiichi Sankyo Co. and Astellas Pharma, Incyte Corporation, and Cyclacel Pharmaceuticals, Inc. A.S.A. has received honoraria from Jazz Pharmaceuticals, Sigma Tau, Pfizer, Amgen, Seattle Genetics, and Kite Pharmaceuticals. S.P.H. owns stock in Amgen; and has received consulting fees from Novartis and honoraria from Amgen. R.A.L. has received consulting fees and/or research support for clinical trials to his institution from Amgen, Ariad/Takeda, Cellectis, Celgene, CVS Caremark, Epizyme, Forty Seven, Novartis, and Rafael Pharmaceuticals. M.C.F. reports research funding from Bellicum and Celgene/BMS; research funding and consulting from MacroGenics; and consulting from Agios. R.M.S. reports grant/personal fees from AbbVie, Agios, and Novartis; grants from AROG; and personal fees from Actinium, Argenx, Astellas, AstraZeneca, BioLineRx, Celgene, Daiichi Sankyo, Elevate, Gemoab, Janssen, Jazz, MacroGenics, Otsuka, Pfizer, Hoffmann-La Roche, Stemline, Syndax, Syntrix, Syros, Takeda, and Trovagene. S.M.L. reports honoraria from Daiichi Sankyo, Jazz, Bristol Myers Squibb, Acceleron, and Agios; research funding from Biosight, Celgene, Hoffmann-La Roche, Kura, Onconova, and Ariad. M.L.L. reports advisory board membership for MediSix Therapeutics, Inc. M.S.T. reports research funding from AbbVie, Cellerant, Orsenix, ADC Therapeutics, Biosight, Glycomimetics, Rafael Pharmaceuticals, and Amgen; advisory board membership for AbbVie, BioLineRx, Daiichi Sankyo, Orsenix, KAHR, Rigel, Nohla, Delta-Fly Pharma, Tetraphase, Oncolyze, Jazz Pharma, Roche, Biosight, and Novartis; and royalties from UpToDate. W.S. reports advisory board memberships for Agios, Amgen, Astellas, Kite, Jazz, MorphoSys, and Servier; speaking honoraria from AbbVie and Pfizer; and other from UpToDate and Research to Practice. The remaining authors declare no competing financial interests.

© 2021 by The American Society of Hematology.

Figures

Graphical abstract

Figure 1.

Comparison of select adverse events (grade 3-4) during induction (age group 16-21 years). ALT, alanine aminotransferase.

Figure 2.

Comparison of select adverse events (grade 3-4) during postremission therapy (age group 16-21 years). ALT, alanine aminotransferase; AST, aspartate aminotransferase. *Decreased fibrinogen level.