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NOTCH1, SF3B1, and TP53 mutations in fludarabine-refractory CLL patients treated with alemtuzumab: results from the CLL2H trial of the GCLLSG

Andrea Schnaiter, Peter Paschka, Marianna Rossi, Thorsten Zenz, Andreas Bühler, Dirk Winkler, Mario Cazzola, Konstanze Döhner, Jennifer Edelmann, Daniel Mertens, Sabrina Kless, Silja Mack, Raymonde Busch, Michael Hallek, Hartmut Döhner and Stephan Stilgenbauer

Data supplements

Article Figures & Data

Figures

  • Figure 1

    Incidences and distributions of genetic markers. (A) Incidences of genetic markers for all patients with mutation data of NOTCH1 and SF3B1 available (n = 97). Rows represent genetic markers and columns represent individual patients, color-coded based on the marker status (red: NOTCH1mut; orange: SF3B1mut; yellow: TP53mut; green: 17p deletion; blue: 11q deletion; purple: trisomy 12; dark blue: 13q deletion; gray: IGHV unmutated [UM]). Hatched gray indicates missing data. (B) Circos diagrams illustrating pairwise co-occurrence of gene mutations with genomic aberrations (left) and with IGHV status (right). Circle segments depict the relative frequency of mutations, aberrations, or IGHV status and their co-occurrence. The width of the ribbons corresponds to the proportion of pairwise co-occurring mutations and aberrations or IGHV status. Unoccupied parts of the segments represent cases with only a single mutation or aberration.

  • Figure 2

    Estimated survival times according to NOTCH1mut and SF3B1mut. PFS was defined as the time from first drug administration to disease progression or death, and was censored at the initiation of subsequent treatment without progression. OS was defined as the time from first drug administration to death, and was censored at the time of allo-SCT. (A) Progression-free survival (PFS) of patients with NOTCH1mut (n = 12; median PFS: 15.47 months) was significantly longer as compared with patients with NOTCH1WT (n = 82: median: 6.74 months) (P = .025). (B) OS of patients with NOTCH1mut (n = 12; median OS: not reached) was not significantly different as compared with patients with NOTCH1WT (n = 82; median OS: 18.3 months) (P = .181). (C) PFS of patients with SF3B1mut (n = 17; median PFS: 4.76 months) was not significantly different as compared with patients with SF3B1WT (n = 77; median PFS: 7.72 months) (P = .974). (D) OS of patients with SF3B1mut (n = 17; median OS: 29.0 months) was not significantly different as compared with patients with SF3B1WT (n = 77; median OS: 17.1 months) (P = .243). WT, wild-type.