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Multicenter Study
. 2019 Jul;121(2):150-156.
doi: 10.1038/s41416-019-0502-x. Epub 2019 Jun 18.

The combination of complex karyotype subtypes and IGHV mutational status identifies new prognostic and predictive groups in chronic lymphocytic leukaemia

Andrea Visentin  1   2 , Laura Bonaldi  3 , Gian Matteo Rigolin  4 , Francesca Romana Mauro  5 , Annalisa Martines  3 , Federica Frezzato  1   2 , Silvia Imbergamo  1   2 , Edoardo Scomazzon  1   2 , Stefano Pravato  1   2 , Maria Antonella Bardi  4 , Maurizio Cavallari  4 , Eleonora Volta  4 , Francesco Cavazzini  4 , Maurizio Nanni  5 , Ilaria Del Giudice  5 , Monica Facco  1   2 , Anna Guarini  5 , Gianpietro Semenzato  1   2 , Robin Foà  5 , Antonio Cuneo  4 , Livio Trentin  6   7
Affiliations
Multicenter Study

The combination of complex karyotype subtypes and IGHV mutational status identifies new prognostic and predictive groups in chronic lymphocytic leukaemia

Andrea Visentin et al. Br J Cancer. 2019 Jul.

Abstract

Background: Complex karyotype (CK) is a heterogeneous category with a negative impact in chronic lymphocytic leukaemia (CLL). Our group has recently reported that CK patients with major structural abnormalities (i.e. CK2) are characterised by a worse prognosis, as compared to other lesions within CK(CK1).

Methods: We performed a multicentre retrospective study to test whether the combination of CK subtypes with IGHV status could be a relevant prognostic and predictive tool.

Results: Among 522 patients 13% harboured CK2, 41% CK1 and/or U-IGHV (U-CK1) and 46% M-IGHV without any CK subtypes (M-noCK). After a median follow-up of 5.8 years, CK2 patients had the shortest TTFT (5-year TTFT 31%, 39 and 81%, p < 0.0001) and OS (5-year OS 67%, 85 and 93%, p < 0.0001) as compared to U-CK1 or M-noCK cases, regardless of TP53 abnormalities. CK2 patients also had the worst outcome after chemoimmunotherapy. In fact, the median TTNT after FCR or BR was 1.86 and 4.79 years for CK2 and U-CK1, but not reached for M-noCK patients (p < 0.0005).

Conclusions: We herein suggest that the combined assessment of the IGHV mutational status and CK subtypes refines the prognostication of CLL, allowing to identify M-IGHV patients without any CK subtypes who are characterised by an indolent disease and excellent outcome after chemoimmunotherapy.

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Conflict of interest statement

A.V. received honoraria from Janssen and Abbvie. L.T. received research funding by Gilead and Janssen, advisory board for Roche, Shire and Abbvie. G.M.R. received research funding by Gilead. F.R.M. advisory board for Janssen, Shire and Abbvie. A.C. advisory board and speaker bureau for Roche, Abbvie, Gilead and Janssen. G.S. board member of Abbvie, Roche, Janssen and Celgene. R.F. advisory board or speaker bureau for Roche, Abbvie, Celgene, Incyte, Amgen, Janssen, Celtrion, Gilead and Novartis. The remaining authors declare no competing interests.

Figures

Fig. 1
Fig. 1
In the upper-left panel a the apple-pie graph represents the distribution of patients harbouring type 2 complex karyotype (CK2, 13%), type 1 CK or unmutated IGHV gene (U-CK1, 41%) and mutated IGHV gene without any CK subtypes (M-noCK, 46%). The upper-right panel b shows histograms for frequencies of biological variables among identified subgroups. CK2 subgroups was significantly enriched for CD38 ≥ 30% (CD38+), 11q deletion (11q−), 17p deletions (17p−), TP53 abnormalities (TP53 abn) cases compared to M-noCK or U-CK1 subjects. Panels c–f show Kaplan–Meier curves for survival analysis. Patients with CK2 (light grey curve) had the shortest time to first treatment (c) and overall survival (d) from diagnosis, as well as the worst time to next treatment (e) and overall survival (f) after chemoimmunotherapy with FCR or BR as compared with U-CK1 (dark grey curves) and M-noCK cases (black curves)
See this image and copyright information in PMC

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