Richter Transformation Tied to Poor Prognosis, High Death Rate in Patients With CLL

In an interview with Oncology Learning Network, Othman Al-Sawaf, MD, Hematologist-Oncologist, University Hospital of Cologne, Germany, and Study Physician, German Chronic Lymphocytic Leukemia (CLL) Study Group, discussed the findings and clinical significance of a pooled analysis evaluating the incidence, characteristics, and outcomes of patients with CLL and Richter transformation (Leukemia. 2020 Mar 17. Epub ahead of print).

What existing data led you and your co-investigators to conduct this research?

The incidence rate of Richter transformation (ie, aggressive transformation from an indolent lymphoma to an aggressive lymphoma) in patients with chronic lymphocytic leukemia has been estimated between 2% and 10%. It is therefore a rare event and data are relatively heterogeneous and sparse when it comes to characteristics and outcomes of such patients.

Please briefly describe your study and its findings.

In order to generate more knowledge on patients with Richter transformation, we wanted to pool all patients from several large phase 2 and phase 3 trials conducted within the German CLL Study Group. The next step was to detect which patients developed Richter transformation at some stage, which characteristics they had and what outcome was reported for those patients.

A total of 2975 patients with advanced CLL were reviewed for incidence of Richter transformation. Of these patients, 103 (3%) developed Richter transformation, including 95 (92%) patients with diffuse large B-cell lymphoma and 8 (8%) patients with Hodgkin lymphoma (8%).

Some adverse risk factors were more common in patients with Richter transformation than in patients without Richter transformation, such as deletion(17p) or very high risk CLL-IPI.

The median overall survival (OS) after diagnosis of Richter transformation was 9.4 months; interestingly, patients with aggressive NHL had a median OS of just 8.7 months, whereas patients with transformation to Hodgkin's lymphoma had a median OS of 82.6 months.

What are the possible real-world applications of these findings in clinical practice?

This analysis demonstrates the dramatically poor outcome of patients with Richter transformation. The majority of patients have been treated with chemo-immunotherapy similar to de-novo diffuse large B-cell lymphoma, but the efficacy of this treatment seems to be considerably limited given the very short OS.

This indicates that we have to find alternative strategies to improve the prognosis of those patients, as conventional chemotherapy approaches obviously fail to achieve sufficient disease control.

Do you and your co-investigators intend to expand upon this research?

We recently started a phase 2 study in which we investigate the combination of a PD1 inhibitor, tislelizumab, and a Bruton’s tyrosine kinase inhibitor, zanubrutinib, in patients with previously untreated, as well as relapsed, Richter transformation.

This trial runs in Germany, Austria, and Denmark, and will show whether patients do respond to such a regimen that is supposed to be more effective and tolerable, particularly for elderly patients, who are the majority of patients with Richter transformation. 

Is there anything else pertaining to your research and findings that you would like to add?

Given that Richter transformation is a rare event, it is important to collect data and samples from those patients in order to characterize and better understand the biology of transformation.

We therefore always recommend managing these patients together with a nearby specialized center and study group, in order to improve our knowledge and the prognosis of patients with Richter transformation.