# From Chronic Lymphocytic Leukemia to Plasmablastic Myeloma: Beyond the Usual Richter Transformation

## TL;DR

A rare case of chronic lymphocytic leukemia transforming into plasmablastic myeloma is reported, highlighting its unique biology and resistance to treatment.

## Contribution

The first documented case of chronic lymphocytic leukemia transforming into plasmablastic myeloma with clonal evidence and distinct clinical features.

## Key findings

- The transformation involved a new del(17p) and TP53 mutation, indicating genetic changes.
- The patient was refractory to standard myeloma therapy and had a rapid fatal outcome.
- Plasmablastic Richter transformation is suggested as a distinct clinical entity requiring classification.

## Abstract

Transformation of chronic lymphocytic leukemia (CLL) into a lymphoproliferative neoplasm with plasmablastic differentiation is exceptionally rare and remains poorly characterized. We report the first case of a patient with CLL developing a clonally related plasmablastic myeloma (PBM). The disease was defined by the emergence of a new del(17p) and TP53 mutation. Clinically, the PBM displayed an aggressive course, with primary refractoriness to frontline daratumumab, bortezomib, lenalidomide, and dexamethasone (Dara-VRd), leading to rapid fatality. This case highlights the importance of recognizing plasmablastic Richter transformation (RT) as a distinct entity in future classifications, given its unique biology and resistance profile compared with classical RT.

Background: Richter transformation (RT) is defined as the histologic transformation of Chronic Lymphocytic Leukemia (CLL) to either diffuse large B-cell lymphoma or Hodgkin lymphoma. Transformation into lymphoproliferative neoplasms with plasmablastic differentiation is exceptionally rare and poorly characterized. Case Presentation: We present the first case of a patient with CLL evolving into plasmablastic myeloma (PBM). A 62-year-old man with previously treated CLL developed thrombocytopenia and rapidly progressive acute kidney injury. Serum electrophoresis showed new IgA-λ protein (2.2 g/L) with λ and κ light chains at 3445.4 and 7.3 mg/L. Bone marrow examination showed extensive infiltration (>95%) by plasmablasts and mature plasma cells, with a consistent immunophenotype (CD38+, CD138+, MUM1+, CD19−, CD20−). In situ hybridization with EBER was negative. Mutation assessment by NGS demonstrated a TP53 mutation and FISH prob panel revealed a new del17p. Clonal relatedness was confirmed by shared IGHV somatic hypermutation using NGS. The patient was primary refractory to frontline myeloma therapy with Dara-VRd and succumbed rapidly to his disease. Discussion: This case illustrates an exceptionally rare form of RT. Recognition and incorporation in new classifications of plasmablastic RT as a distinct entity is critical, as its biology and resistance profile differ from classical RT.