High sIgM levels or signaling capacity associates with shorter TTNT following ibrutinib therapy. SIgM levels and signaling capacity were measured by flow cytometry before start of ibrutinib. (A) Patients with sIgM MFI > 50 (red line) and sIgM MFI < 50 (blue line) were investigated for time to progression requiring a new treatment from ibrutinib start (TTNT). (B) Patients with high sIgM iCa²⁺ (red line, >39% iCa²⁺ using ROC and Youden’s t test) and low signaling (blue line, <39% iCa²⁺) were also investigated for TTNT. The y-axis (%) indicates the cumulative proportion of patients surviving without having progressed to a new treatment need. Cumulative survival analysis was performed by Kaplan-Meier algorithm using log-rank statistics.