Patient-Level Meta-analysis of Clofarabine in Acute Lymphoblastic Leukemia

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Abstract

Introduction

Clofarabine monotherapy at a dose of 52 mg/m ² per day was approved in the USA in 2004 for the treatment of relapsed or refractory acute lymphoblastic leukemia (R/R ALL) in patients aged 1–21 years after at least two prior regimens. To address a post-marketing requirement for additional evidence of the clinical benefit of clofarabine in its approved indication, a meta-analysis of patient-level data was conducted.

Methods

A systematic literature review was conducted, using the Dr.Evidence software platform, DOC Search, and Embase, to identify clinical trials with patients with R/R ALL who received clofarabine monotherapy at 52 mg/m ². The primary endpoint was complete remission (CR). Secondary endpoints were overall remission (OR, defined by CR or CR with either incomplete platelet recovery or incomplete neutrophil and platelet recovery), duration of response, overall survival (OS), and safety.

Results

A total of 754 patients in 12 clinical studies were analyzed including 682 patients with R/R ALL treated with clofarabine monotherapy at 52 mg/m ²; of them, 374 were aged < 22 years (pediatric population). Rates of CR and OR were 16% (95% confidence interval [CI] 7, 26) and 28% (95% CI 20, 37), respectively, in the pediatric population and 12% (95% CI 5, 21) and 21% (95% CI 13, 31) in the overall population. Median OS (evaluable in three studies in pediatric patients) was 3.7 months (95% CI 0.1, 31.4), reaching 10.1 months (95% CI 0.3, 68.9) for those achieving OR. Sensitivity analyses supported these findings. The most frequent grade 3–4 adverse events were liver abnormalities, anemia, diarrhea, and febrile neutropenia.

Conclusion

In this meta-analysis, CR duration and median OS in pediatric patients with R/R ALL appeared to be slightly longer than in the phase II study. No new safety signals were identified. Results support the use of clofarabine monotherapy in its approved indication.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12325-023-02696-7.

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Author and article information

Contributors

Sima Jeha: sima.jeha@stjude.org

Journal

Journal ID (nlm-ta): Adv Ther

Journal ID (iso-abbrev): Adv Ther

Title: Advances in Therapy

Publisher: Springer Healthcare (Cheshire )

ISSN (Print): 0741-238X

ISSN (Electronic): 1865-8652

Publication date (Electronic): 11 October 2023

Publication date PMC-release: 11 October 2023

Publication date (Print): 2023

Volume: 40

Issue: 12

Pages: 5447-5463

Affiliations

[1 ]St Jude Children’s Hospital Research, ( https://ror.org/02r3e0967) 262 Danny Thomas Place, Memphis, TN 38105-3678 USA

[2 ]Division of Hematology/Oncology, Kanagawa Children’s Medical Center, ( https://ror.org/022h0tq76) Minami-ku, Yokohama, Kanagawa Japan

[3 ]GRID grid.413235.2, ISNI 0000 0004 1937 0589, Department of Pediatric Hemato-Immunology, , Hôpital Universitaire Robert Debré (APHP and Université Paris Cité), ; Paris, France

[4 ]Sanofi, Department of Statistics R&D, ( https://ror.org/02n6c9837) 1 avenue Pierre Brossolette, 91385 Chilly-Mazarin, France

[5 ]Sanofi, Global Medical Oncology, ( https://ror.org/02n6c9837) 46 avenue de la Grande Armée, 75017 Paris, France

[6 ]GRID grid.487647.e, Princess Máxima Center for Pediatric Oncology, ; Utrecht, The Netherlands

[7 ]Department of Pediatrics, Seoul National University Children’s Hospital, Seoul National University College of Medicine, Seoul, Korea

Article

Publisher ID: 2696

DOI: 10.1007/s12325-023-02696-7

PMC ID: 10611855

PubMed ID: 37819554

SO-VID: e98c4ce5-b2e3-443d-87e8-4ee5ada8ff66

License:

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

History

Date received : 4 August 2023

Date accepted : 22 September 2023

Funding

Funded by: FundRef http://dx.doi.org/10.13039/100014588, Sanofi Pasteur;

Custom metadata

Keywords: acute lymphoblastic leukemia,clofarabine,pediatric,oncology,hematological malignancies

Data availability:

Keywords: acute lymphoblastic leukemia, clofarabine, pediatric, oncology, hematological malignancies

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