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Review
. 2023 Dec 8;2023(1):427-432.
doi: 10.1182/hematology.2023000442.

Richter transformation-is there light at the end of this tunnel?

Toby A Eyre  1
Affiliations
Review

Richter transformation-is there light at the end of this tunnel?

Toby A Eyre. Hematology Am Soc Hematol Educ Program. .

Abstract

Richter transformation (RT) represents an uncommon (2% to 10%) but feared complication of chronic lymphocytic leukemia (CLL). The disease is characterized by rapid disease kinetics, a high-risk genetic mutational profile, chemoimmunotherapy resistance, and consequent poor survival. The typical overall survival (OS) from the pre-Bruton tyrosine kinase (BTK)/B-cell lymphoma 2 (BCL2) inhibitor CLL era is 6-12 months, and recent series of RT complicating progression on a BTK or BCL2 inhibitor in heavily pretreated relapsed CLL patients suggests an OS of only 3-4 months. Despite these sobering survival statistics, novel agents have the potential to impact the natural RT disease course. This article reviews recent therapeutic developments, focusing on inhibitors of BTK, BCL2, the PD1-PDL1 axis, and T-cell-activating/engaging therapies. Herein, I discuss the importance of randomized clinical trials in a disease where small single-arm studies dominate; industry engagement, including the role of registrational studies; and the need to integrate prospectively planned correlative biological studies embedded within future clinical trials to help discover which patient benefits most from each class or combination of novel targets.

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Conflict of interest statement

Toby A. Eyre: Roche: education honorarium, advisory board honorarium, travel to scientific conferences; Gilead: honorarium; research support, travel to scientific conferences; KITE: education honorarium, advisory board honorarium; Janssen: honorarium; AbbVie: honorarium, travel to scientific conferences; AstraZeneca: honorarium, research funding, travel to scientific conferences; Loxo Oncology: advisory board honorarium, trial steering committee; Beigene: advisory board honorarium, research funding; Incyte: advisory board honorarium; Secura Bio: advisory board honorarium; Autolus: advisory board honorarium.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
The clinical challenge of RT.
See this image and copyright information in PMC

References

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