Clofarabine monotherapy in aggressive, relapsed and refractory Langerhans cell histiocytosis

Deevyashali Parekh; Howard Lin; Akanksha Batajoo; Erin Peckham-Gregory; Vivekanudeep Karri; Whitney Stanton; Brooks Scull; Ryan Fleishmann; Nader El-Mallawany; Olive S Eckstein; Zachary D Prudowsky; Nitya Gulati; Jennifer E Agrusa; Asra Z Ahmed; Roland Chu; Matthew S Dietz; Stanton C Goldman; Michael D Hogarty; Hamayun Imran; Stefanos Intzes; Jenny M Kim; Lisa M Kopp; Carolyn Fein Levy; Philip Neff; Pallavi M Pillai; Bryan A Sisk; Deborah E Schiff; Angela D Trobaugh-Lotrario; Kelly Walkovich; Kenneth L McClain; Carl E Allen

doi:10.1111/bjh.19376

Clofarabine monotherapy in aggressive, relapsed and refractory Langerhans cell histiocytosis

Br J Haematol. 2024 May;204(5):1888-1893. doi: 10.1111/bjh.19376. Epub 2024 Mar 19.

Authors

Deevyashali Parekh^{1

2}, Howard Lin^{1

2}, Akanksha Batajoo^{1

2}, Erin Peckham-Gregory^{1

2}, Vivekanudeep Karri^{1

2}, Whitney Stanton^{1

2}, Brooks Scull^{1

2}, Ryan Fleishmann^{1

2}, Nader El-Mallawany^{1

2}, Olive S Eckstein^{1

2}, Zachary D Prudowsky^{1

2}, Nitya Gulati^{1

2

3}, Jennifer E Agrusa^{1

2

4}, Asra Z Ahmed⁵, Roland Chu⁶, Matthew S Dietz⁷, Stanton C Goldman⁸, Michael D Hogarty⁹, Hamayun Imran¹⁰, Stefanos Intzes¹¹, Jenny M Kim¹², Lisa M Kopp¹³, Carolyn Fein Levy¹⁴, Philip Neff¹⁵, Pallavi M Pillai¹⁶, Bryan A Sisk¹⁷, Deborah E Schiff¹², Angela D Trobaugh-Lotrario¹¹, Kelly Walkovich⁴, Kenneth L McClain^{1

2}, Carl E Allen^{1

2}

Affiliations

¹ Texas Children's Cancer Center, Texas Children's Hospital, Houston, Texas, USA.
² Department of Pediatrics, Division of Pediatric Hematology and Oncology, Baylor College of Medicine, Houston, Texas, USA.
³ Department of Pediatrics, Weill Cornell Medical College, New York, New York, USA.
⁴ Division of Pediatric Hematology/Oncology, C.S. Mott Children's Hospital, University of Michigan Medical School, Ann Arbor, Michigan, USA.
⁵ Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA.
⁶ Division of Hematology/Oncology/BMT, Central Michigan University College of Medicine, Children's Hospital of Michigan, Detroit, Michigan, USA.
⁷ Division of Pediatric Hematology and Oncology, University of Utah, Primary Children's Hospital, Salt Lake City, Utah, USA.
⁸ Pediatric Hematology/Oncology, Medical City Children's Hospital, Dallas, Texas, USA.
⁹ Division of Oncology, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁰ Department of Pediatrics, University of South Alabama, Mobile, Alberta, USA.
¹¹ Department of Pediatric Hematology/Oncology, Sacred Heart Children's Hospital, Spokane, Washington, USA.
¹² Department of Pediatrics, Division of Hematology/Oncology, University of California San Diego School of Medicine, Rady Children's Hospital, San Diego, California, USA.
¹³ Department of Pediatrics, University of Arizona, Mel and Enid Zuckerman College of Public Health, Tucson, Arizona, USA.
¹⁴ Division of Pediatric Hematology/Oncology, Department of Pediatrics, Cohen Children's Medical Center, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.
¹⁵ Children's Blood and Cancer Center, The University of Texas at Austin, Dell Children's Medical Center of Central Texas, Austin, Texas, USA.
¹⁶ Jack Martin Division of Pediatric Hematology-Oncology, Jack and Lucy Clark Department of Pediatrics, Mount Sinai Kravis Children's Hospital, New York, New York, USA.
¹⁷ Division of Pediatric Hematology and Oncology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.

PMID: 38501389
DOI: 10.1111/bjh.19376

Abstract

Over 50% of patients with systemic LCH are not cured with front-line therapies, and data to guide salvage options are limited. We describe 58 patients with LCH who were treated with clofarabine. Clofarabine monotherapy was active against LCH in this cohort, including heavily pretreated patients with a systemic objective response rate of 92.6%, higher in children (93.8%) than adults (83.3%). BRAF^V600E+ variant allele frequency in peripheral blood is correlated with clinical responses. Prospective multicentre trials are warranted to determine optimal dosing, long-term efficacy, late toxicities, relative cost and patient-reported outcomes of clofarabine compared to alternative LCH salvage therapy strategies.

Keywords: Langerhans cell histiocytosis; clofarabine; myeloid neoplasia.

MeSH terms

Adenine Nucleotides / administration & dosage
Adenine Nucleotides / adverse effects
Adenine Nucleotides / therapeutic use
Adolescent
Adult
Aged
Arabinonucleosides / administration & dosage
Arabinonucleosides / adverse effects
Arabinonucleosides / therapeutic use
Child
Child, Preschool
Clofarabine* / administration & dosage
Clofarabine* / therapeutic use
Female
Histiocytosis, Langerhans-Cell* / drug therapy
Humans
Infant
Male
Middle Aged
Proto-Oncogene Proteins B-raf / genetics
Recurrence
Salvage Therapy
Treatment Outcome
Young Adult

Substances

Clofarabine
Proto-Oncogene Proteins B-raf
BRAF protein, human
Adenine Nucleotides
Arabinonucleosides

Abstract

MeSH terms

Substances

Grants and funding