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.