Monitoring sCSF1R levels during treatment
sCSF1R levels at week 6 of induction therapy were determined in 23 available plasma samples. After the 6-week course of initial induction treatment, ten patients were evaluated as active-disease (AD)-better, six patients were considered AD-stable, and seven patients developed progression and were evaluated as AD-worse. sCSF1R levels decreased significantly in the 16 patients who had AD-better/stable responses (P < 0.0001), whereas sCSF1R remained at high levels in those seven patients with disease progression (Figure 5A).
sCSF1R was sequentially monitored during dabrafenib treatment in thirteen MS LCH patients with theBRAF -V600E mutation (Supplementary Table S2). Six patients experienced relapse after discontinuation of dabrafenib (Figure 5B-G). The levels of sCSF1R obviously decreased after the initiation of dabrafenib administration but increased again at relapse, which was in accordance with the trend of cfBRAF- V600E. Notably, five (patients 1, 2, 4, 5 and 6) of the six patients had elevated sCSF1R levels 1-3 months before the clinical or radiographic appearance of recurrent lesions, which increased earlier than that of cfBRAF- V600E, indicating that sCSF1R levels provided a lead-time advantage over cfBRAF- V600E in predicting relapse (Figure 5B-G).
Of the seven patients who remained in remission, three had drug discontinuation (patients 7 to 9; Supplementary Figure S4A), and four had continuation (patients 10 to 13; Supplementary Figure S4B), and their sCSF1R levels were maintained at low levels during follow-up. Details of the longitudinal changes in sCSF1R and cfBRAF -V600E levels during dabrafenib treatment are shown in Supplementary Table S3.