Near-tetraploidy is associated with Richter transformation in chronic lymphocytic leukemia patients receiving ibrutinib.

Miller CR, Ruppert AS, Heerema NA, Maddocks KJ, Labanowska J, Breidenbach H, Lozanski G, Zhao W, Gordon AL, Jones JA, Flynn JM, Jaglowski SM, Andritsos LA, Blum KA, T Awan F, Rogers KA, Grever MR, Johnson AJ, Abruzzo LV, Hertlein EK, Blachly JS, Woyach JA, Byrd JC
Blood Adv 1 1584-1588 08/22/2017

Abstract

Ibrutinib is a highly effective targeted therapy for chronic lymphocytic leukemia (CLL). However, ibrutinib must be discontinued in a subset of patients due to progressive CLL or transformation to aggressive lymphoma (Richter transformation). Transformation occurs early in the course of therapy and has an extremely poor prognosis. Thus, identification of prognostic markers associated with transformation is of utmost importance. Near-tetraploidy (4 copies of most chromosomes within a cell) has been reported in various lymphomas, but its incidence and significance in CLL has not been described. Using fluorescence in situ hybridization, we detected near-tetraploidy in 9 of 297 patients with CLL prior to beginning ibrutinib treatment on 1 of 4 clinical trials (3.0%; 95% confidence interval [CI], 1.4%-5.7%). Near-tetraploidy was associated with aggressive disease characteristics: Rai stage 3/4 (

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