Severe pegaspargase hypersensitivity reaction rates (grade ≥3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children's oncology group (COG) clinical trials

Michael J Burke; Meenakshi Devidas; Kelly Maloney; Anne Angiolillo; Reuven Schore; Kimberly Dunsmore; Eric Larsen; Len A Mattano Jr; Wanda Salzer; Stuart S Winter; William Carroll; Naomi J Winick; Mignon L Loh; Elizabeth Raetz; Stephen P Hunger; Archie Bleyer

doi:10.1080/10428194.2017.1397658

Severe pegaspargase hypersensitivity reaction rates (grade ≥3) with intravenous infusion vs. intramuscular injection: analysis of 54,280 doses administered to 16,534 patients on children's oncology group (COG) clinical trials

Leuk Lymphoma. 2018 Jul;59(7):1624-1633. doi: 10.1080/10428194.2017.1397658. Epub 2017 Nov 8.

Authors

Michael J Burke¹, Meenakshi Devidas², Kelly Maloney³, Anne Angiolillo⁴, Reuven Schore⁴, Kimberly Dunsmore⁵, Eric Larsen⁶, Len A Mattano Jr⁷, Wanda Salzer⁸, Stuart S Winter⁹, William Carroll¹⁰, Naomi J Winick¹¹, Mignon L Loh¹², Elizabeth Raetz¹³, Stephen P Hunger¹⁴, Archie Bleyer¹⁵

Affiliations

¹ a Medical College of Wisconsin and Children's Hospital of Wisconsin , Milwaukee , WI , USA.
² b Department of Biostatistics , University of Florida , Gainesville , FL , USA.
³ c School of Medicine and Children's Hospital of Colorado, University of Colorado , Aurora , CO , USA.
⁴ d Children's National Medical Center , Washington , DC , USA.
⁵ e University of Virginia Children's Hospital , Charlottesville , VA , USA.
⁶ f Maine Children's Cancer Program , Scarborough , ME , USA.
⁷ g HARP Pharma Consulting , Mystic , CT , USA.
⁸ h US Army Medical Research and Materiel Command , Fort Detrick , MD , USA.
⁹ i Health Sciences Center, University of New Mexico , Albuquerque , NM , USA.
¹⁰ j Laura and Issac Perlmutter Cancer Center at NYU , New York , NY , USA.
¹¹ k Southwestern Simmons Cancer Center, University of Texas , Dallas , TX , USA.
¹² l Benioff Children's Hospital, University of California San Francisco , San Francisco , CA , USA.
¹³ m Department of Pediatrics , University of Utah , Salt Lake City , UT , USA.
¹⁴ n Children's Hospital of Philadelphia, The Perelman School of Medicine, University of Pennsylvania , Philadelphia , PA , USA.
¹⁵ o Department of Pediatrics , Oregon Health and Science University , Portland , OR , USA.

Abstract

PEGylated asparaginase (pegaspargase) can be administered via intramuscular (IM) injection or intravenous (IV) infusion with a hypersensitivity reaction (HSR) incidence ranging 3-41%. We evaluated grade ≥3 HSRs when given IM vs. IV on six Children's Oncology Group (COG) leukemia trials (2003-2015) to determine differences in HSR rates. 54,280 doses were administered to 16,534 patients. Considering all doses of pegaspargase during induction, consolidation, and delayed intensification, grade ≥3 HSR rate with IM injection was 5.4% (n = 482/8981) compared to 3.2% for IV (n = 245/7553) (p < .0001). If only the second and third doses of pegaspargase were analyzed, where the majority of grade ≥3 HSRs occur, the rate following IM injection was 10.1% (n = 459/4534) compared to 5.0% (n = 222/4443) for IV (p < .0001). On standardized treatment protocols conducted by the COG during 2003-2015, grade ≥3 HSR rates to pegaspargase occurred less frequently with IV infusion than IM injection.

Keywords: ALL; Pegaspargase; asparaginase; hypersensitivity; intramuscular; intravenous.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adolescent
Age Factors
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / adverse effects*
Antineoplastic Agents / therapeutic use
Asparaginase / administration & dosage
Asparaginase / adverse effects*
Asparaginase / therapeutic use
Biomarkers
Child
Child, Preschool
Drug Hypersensitivity / diagnosis
Drug Hypersensitivity / epidemiology*
Drug Hypersensitivity / etiology*
Female
Humans
Incidence
Infusions, Intravenous
Injections, Intramuscular
Leukemia / complications
Leukemia / drug therapy
Male
Polyethylene Glycols / administration & dosage
Polyethylene Glycols / adverse effects*
Polyethylene Glycols / therapeutic use
Public Health Surveillance
Severity of Illness Index

Substances

Antineoplastic Agents
Biomarkers
Polyethylene Glycols
pegaspargase
Asparaginase

Abstract

Publication types

MeSH terms

Substances

Grants and funding