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. 2023 Sep 26;7(18):5234-5245.
doi: 10.1182/bloodadvances.2023009976.

Effect of BMI on toxicities and survival among adolescents and young adults treated on DFCI Consortium ALL trials

Shai Shimony  1   2 , Yael Flamand  3 , Yannis K Valtis  4 , Andrew E Place  5 , Lewis B Silverman  5 , Lynda M Vrooman  5 , Andrew M Brunner  6 , Stephen E Sallan  5 , Richard M Stone  1 , Martha Wadleigh  1 , Donna S Neuberg  3 , Daniel J DeAngelo  1 , Marlise R Luskin  1
Affiliations

Effect of BMI on toxicities and survival among adolescents and young adults treated on DFCI Consortium ALL trials

Shai Shimony et al. Blood Adv. .

Abstract

Adolescent and young adults (AYAs) with acute lymphoblastic leukemia (ALL) treated with asparaginase-containing pediatric regimens are commonly overweight or obese. We studied the association of body mass index (BMI) on outcomes of 388 AYAs aged 15 to 50 years treated on Dana-Farber Cancer Institute (DFCI) consortium regimens (2008-2021). BMI was normal in 207 (53.3%) and overweight/obese in 181 (46.7%). Patients who were overweight or obese experienced higher nonrelapse mortality (NRM; 4-year, 11.7% vs 2.8%, P = .006), worse event-free survival (4-year, 63% vs 77%, P = .003), and worse overall survival (OS; 4-year, 64% vs 83%, P = .0001). Because younger (aged 15-29 years) AYAs more frequently had a normal BMI (79% vs 20%, P < .0001), we conducted separate analyses in each BMI group. We found excellent OS among younger and older (30-50 years) AYAs with normal BMI (4-year OS, 83% vs 85%, P = .89). Conversely, in AYAs who were overweight/obese, worse outcomes were seen in older AYAs (4-year OS, 55% vs 73%, P = .023). Regarding toxicity, AYAs who were overweight/obese experienced higher rates of grade 3/4 hepatotoxicity and hyperglycemia (60.7% vs 42.2%, P = .0005, and 36.4% vs 24.4%, P = .014, respectively) but had comparable rates of hypertriglyceridemia (29.5% vs 24.4%, P = .29). In a multivariable analysis, higher BMI was associated with worse OS, hypertriglyceridemia was associated with improved OS, and age was not associated with OS. In conclusion, among AYAs treated on DFCI Consortium ALL regimens, elevated BMI was associated with increased toxicity, increased NRM, and decreased OS. The deleterious effect of elevated BMI was more pronounced in older AYAs.

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Conflict of interest statement

Conflict-of-interest disclosure: L.B.S. reports serving on advisory boards for Jazz, Servier, and Syndax. A.M.B. reports research support from AstraZeneca, Novartis, Roivant, Takeda, Celgene/Bristol Myers Squibb (BMS), GlaxoSmithKline (GSK), and Janssen, and consulting fees from Agios, AbbVie, Acceleron, BMS/Celgene, Novartis, Gilead, Keros Therapeutics, and Taiho Oncology. S.E.S. reports honoraria from Jazz and Servier. R.M.S. reports consulting fees from AbbVie, AbbVie/Genetech, Actinium, Amgen, Aptevo, Aprea, Arog, AvenCell, BerGenBio, BMS, Boston Pharmaceuticals, Cellularity, CTI Pharma, Epizyme, Foghorn Therapeutics, Gemoab, GSK, Innate, Janssen, Jazz, Kura Oncology, Novartis, Onconova, Rigel, Syntrix, Syros, and Takeda. D.S.N. reports consultancy with The American Society of Hematology Research Collaborative as a senior scientific adviser and reports stock ownership in Madrigal Pharmaceuticals. D.J.D. has served as a consultant for Amgen, Autolos, Agios, Blueprint Pharmaceuticals, Forty-Seven, Gilead, Incyte, Jazz, Novartis, Pfizer, Servier, and Takeda, and received research funding from AbbVie, Glycomimetics, Novartis, and Blueprint Pharmaceuticals. M.R.L. receives research support from AbbVie and Novartis, and has served on advisory boards for Novartis, Jazz, and Pfizer. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
ALL DFCI consortium treatment protocols. Including pediatric protocols (00-001 and 05-001) and pediatric-inspired protocols (01-175 and 06-254). Asparaginase administration is marked in red. CNS, central nervous system.
Figure 2.
Figure 2.
Comparison of grade 3/4 toxicity rates between BMI groups (normal vs overweight/obese). TG, hypertriglyceridemia.
Figure 3.
Figure 3.
Kaplan-Meier survival per BMI and age group. (A) OS; (B) EFS.
Figure 4.
Figure 4.
CIR by BMI and age group. (A) All patients by BMI group. (B) Patients with normal BMI by age group. (C) Overweight/obese patients by age group.
Figure 5.
Figure 5.
Nonrelapse mortality by BMI and age group. (A) All patients by BMI group. (B) Patients with normal BMI by age group. (C) Overweight/obese patients by age group.
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Comment in

References

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