Abstract
Langerhans cell histiocytosis (LCH) is a clonal histiocytic neoplasm with various clinical manifestations and heterogeneous prognoses. No standard therapy is available for recurrent/refractory LCH patients. This single-center, single-arm, phase 2 study enrolled 32 patients diagnosed with recurrent/refractory LCH. The TCD regimen (thalidomide 100 mg daily, cyclophosphamide 300 mg/m2 Day 1, 8, 15, and dexamethasone 40 mg Day 1, 8, 15, 22 every 4 weeks) was administered for 12 cycles and thalidomide alone as maintenance for 12 months. The primary endpoint was event-free survival (EFS). Events were defined as progression during or after TCD therapy or death from any cause. After a median follow-up of 22 months (range 5–24 months), no patient died of all causes. The overall response rate was 87.5%, including 18 patients (56.3%) achieving complete remission and 10 patients (31.3%) as partial remission. The estimated 24-month EFS was 64.0%. Patients with risk organ involvement had similar EFS compared to patients without risk organ involvement (P = 0.38). The common toxicities of TCD regimen include grade 1–2 neutropenia (18.8%), grade 1–2 constipation (12.5%), grade 1–2 tiredness (9.4%) and grade 2 peripheral neuropathy (12.5%). Oral thalidomide, cyclophosphamide and dexamethasone are effective and safe regimen for recurrent/refractory LCH patients, particularly for patients with risk organ involvement.
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Data availability
Individual participant data will not be available. The study protocol will be available beginning 9 months and ending 36 months following article publication at caoxinxin@126.com. Deidentified individual participant data are available indefinitely in Supplementary Table 1.
Change history
08 February 2023
A Correction to this paper has been published: https://doi.org/10.1038/s41375-023-01812-4
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Acknowledgements
The authors thank all the patients and their families for their trust, respect and support. They also acknowledge all clinicians for their help in accomplishing this work.
Funding
This work was supported by the Beijing Natural Science Foundation (Grant No. 7202160) (XC), the Central Research Institute Fund of the Chinese Academy of Medical Sciences (2019-RC-HL-001) (XC).
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Drs XC and JW had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: XC, and MD. Acquisition, analysis, or interpretation of data: JW, TL, and AZ. Drafting of the paper: JW, and TL. Review all pathological findings: JS and BP. Critical revision of the paper for important intellectual content: JL, DZ, XC, and MD. Obtained funding: XC. All authors reviewed and approved the final paper.
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Wang, Jn., Liu, T., Zhao, Al. et al. Phase 2 study of oral thalidomide-cyclophosphamide-dexamethasone for recurrent/refractory adult Langerhans cell histiocytosis. Leukemia 36, 1619–1624 (2022). https://doi.org/10.1038/s41375-022-01555-8
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DOI: https://doi.org/10.1038/s41375-022-01555-8
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