The indication was periprocedural and the total duration of interruption was 14 days in each of the 3 cases. Management of Richter transformation was restarting ibrutinib in all cases.

IGHV, immunoglobulin heavy chain gene; iwCLL, International Workshop on Chronic Lymphocytic Leukemia; N/A, not applicable; NGS, next-generation sequencing results; PR, partial remission; Pt, unique patient; RT, Richter transformation; TTNT, time to next treatment; Unmut, unmutated.

Dose reduced from 420 mg daily after 6 months of treatment due to easy bruising.

Tempus next-generation sequencing performed on the DLBCL surgical pathology specimen. This revealed multiple TP53 aberrations (c.376-1G>A splice region variant resulting in loss of function [22.77% allelic frequency], p.Y220C missense variant resulting in loss of function [6.97% allelic frequency], and p.C135W missense variant resulting in loss of function [6.54% allelic frequency]). Also noted were 2 variants in GPS2, a gene encoding a protein involved in the MAPK pathway (c.204+2T>G splice region variant resulting in loss of function [6.42% allelic frequency] and p.M153fs frameshift resulting in loss of function [2.90% allelic frequency]). Tumor mutational burden was 2.2 nonsynonymous mutations/Mb. RNA sequencing performed through Tempus noted overexpression of BCL2, CREBBP, and MTOR.

Fludarabine and cyclophosphamide; pentostatin, cyclophosphamide, and rituximab; cyclophosphamide and rituximab; bendamustine; lenalidomide and dexamethasone; second course of pentostatin, cyclophosphamide, and rituximab; fludarabine, cyclophosphamide, and rituximab; ofatumumab; and rituximab and methylprednisolone.