Therapeutic interventions linked with lower toxicity, as well as better targeted therapies, may help to improve outcomes among patients who develop Richter transformation (RT), according to the authors of an article published in the Journal of Clinical Oncology.

RT is defined by the development of aggressive lymphoma among patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Patients with CLL/SLL face a 2%-10% risk of progression to RT, with an approximate risk per year of 0.5%-1%.

However, there is significant heterogeneity in this patient population, and as a result, different studies give different estimates of overall patient risk. For example, patients with heavily pretreated disease may be at a higher risk, whereas patients receiving first-line targeted therapy may have a risk as low as 0%.

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Most patients who progress to RT have diffuse large B-cell lymphoma (DLBCL), though RT has been noted in other lymphoma subtypes. In the present paper, researchers discussed emerging therapies likely to be of value in the subpopulation of patients who develop RT.

The authors noted that RT development signs to watch for include the development of B symptoms, rapidly progressive asymmetric lymphadenopathy, and a notable rise in serum lactate dehydrogenase levels. In these cases, they recommend clincians order a biopsy with subsequent review by an experienced hematopathologist.

Although a number of clinical characteristics — including serum lactate dehydrogenase levels — are predictive of outcomes among patients with RT, a patient’s CLL/SLL treatment status is also a critical component of prognosis. Patients who have received targeted inhibitors, for example, have an estimated median overall survival of less than 4 months.

The authors reviewed published data to determine therapeutic strategies likely to be beneficial among patients who develop RT. These include B-cell inhibition, CD20-targeting therapies, CD19-targeting chimeric antigen receptor (CAR)-T therapies, and checkpoint inhibitors. However, they noted that particularly in the case of CAR-T therapy, large, prospective trials are needed to confirm early — but encouraging — results.

“In conclusion, with a plethora of highly active novel agents in development, the future for patients with RT looks brighter,” the authors wrote in their report. “Combinations of immunotherapies and targeted inhibitors appear particularly promising, and randomized studies combining these agents or adding them to [chemoimmunotherapy] may avoid problems with treatment resistance.”

Disclosure: Some of the study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


Smyth E, Eyre TA, Cheah CY. Emerging therapies for the management of Richter transformation. J Clin Oncol. Published online September 21, 2022. doi:10.1200/JCO.22.01028