3.1 Clinical characteristics of LCH patients
The clinical characteristics of enrolled patients were shown in Table 1. There were 230 (62.2%) males and 140 (37.8%) females. The median age at diagnosis of LCH was 3.1 years (ranging from 0.1 to 15.1 years). Two hundred and twenty-four (60.5%) patients were classified with SS LCH, 95 (25.7%) with MS RO- LCH, and 51 (13.8%) with MS RO+ LCH. The most commonly affected organ was the bone (91.4%), followed by the skin (20.0%), lung (15.9%), liver (11.6%) and lymph nodes (11.1%). In fewer cases, spleen (7.3%), hematologic system (7.0%), ear (6.2%), pituitary (5.4%), and eye (3.0%) were affected. Non-pituitary central nervous system (CNS) was rarely involved (1.4%). Among 311 evaluable patients, 55.3% of cases harboredBRAF -V600E mutations, 18.0% carried MAP2K1 mutations, and 9.3% had BRAF other mutations. Furthermore, cfBRAF -V600E mutations were detected positive in 33.2% of 313 patients with available plasma samples for testing.
A comparison of the two cohorts revealed younger patients in the test cohort (P = 0.003), more bone (P = 0.003), and less skin (P = 0.005) involvement in the validation cohort. Besides, more frequent MAP2K1 mutations in tissue lesions (P < 0.001) and fewer BRAF -V600E mutations in plasma cfDNA (P = 0.011) were found in the validation cohort compared to the test cohort. Other baseline characteristics including gender, disease extents categorization, and other organ involvements were not significantly different between the test and validation cohort (Table 1). Other eleven patients with BRAF -V600E mutations directly received dabrafenib treatment, seven were MS RO+, and four MS RO-. The majority of patients (90.9%) were under two years old.
The 3-year PFS was 61.7% ± 2.6% for the whole cohort, with a median follow-up time of 33.4 months. Only one patient died of cirrhosis after first-line and second-line chemotherapy and targeted therapy. The median follow-up time was longer for the test cohort than the validation cohort (62.0 months vs. 32.1 months, P < 0.001). The estimated median PFS time for the test and validation cohorts was 50.0 months and 42.7 months, respectively. Among the eleven patients treated with dabrafenib, six patients discontinued dabrafenib and four of them relapsed.
TABLE 1 clinical characteristics of enrolled patients with Langerhans cell histiocytosis