Phase 2 study using low dose cytarabine for adult patients with newly diagnosed Langerhans cell histiocytosis

• Published in: Leukemia Vol. 38; no. 4; pp. 803 - 809
• Main Authors: Chang, Long, Lang, Min, Lin, He, Cai, Hao, Duan, Ming-Hui, Zhou, Dao-Bin, Cao, Xin-Xin
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.04.2024
• Subjects: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Autoimmune diseases; Cytarabine; Disease-Free Survival; Histiocytosis; Histiocytosis, Langerhans-Cell - diagnosis; Histiocytosis, Langerhans-Cell - drug therapy; Humans; Lungs; MAP kinase; Medical prognosis; Middle Aged; Multivariate analysis; Neutropenia; Next-generation sequencing; Organs; p53 Protein; Prospective Studies; Thrombocytopenia; Young Adult
• ISSN: 0887-6924; 1476-5551; 1476-5551
• DOI: 10.1038/s41375-024-02174-1

Langerhans cell histiocytosis (LCH) lacks a standardized first-line therapy. This single-center, phase 2 prospective study (NCT04121819) enrolled 61 newly diagnosed adult LCH patients with multisystem or multifocal single system disease from October 2019 to June 2022. Subcutaneous cytarabine (100 mg/m2 for 5 days) was administered in 35-day cycles for 12 total cycles. The primary endpoint was event-free survival (EFS). The median age was 33 years (range 18-66). Twelve patients (19.7%) had liver involvement, of which 2 also had spleen involvement. Among 43 patients undergoing next-generation sequencing, BRAF alterations (44.2%) were most frequent, followed by TP53 (16.3%), MAP2K1 (14.0%) and IDH2 (11.6%). MAPK pathway alterations occurred in 28 patients (65.1%). The overall response rate was 93.4%, with 20 (32.7%) achieving complete response and 37 (60.7%) partial response. After a median 30 months follow-up, 21 (34.4%) relapsed without deaths. Estimated 3-year OS and EFS were 100.0% and 58.5%, respectively. Multivariate analysis identified ≥3 involved organs (P = 0.007; HR 3.937, 95% CI: 1.456-9.804) and baseline lung involvement (P = 0.028; HR 2.976, 95% CI: 1.126-7.874) as poor prognostic factors for EFS. The most common grade 3-4 toxicities were neutropenia (27.9%), thrombocytopenia (1.6%), and nausea (1.6%). In conclusion, cytarabine monotherapy is an effective and safe regimen for newly diagnosed adults, while baseline lung or ≥3 involved organs confers poor prognosis.