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.

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.

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