Navigating the Logistical and Clinical Hurdles of Richter Transformation

The treatment landscape for Richter transformation and aggressive B-cell lymphomas is undergoing a rapid molecular evolution, yet clinical success remains tethered to the last mile of care: patient access and inter-institutional collaboration. While the emergence of chimeric antigen receptor (CAR) T-cell therapy has the potential to triple cure rates in large cell lymphoma, current estimates suggest only 25% to 30% of eligible patients receive these life-saving interventions.

In an interview with Targeted Oncology, Marc S. Hoffmann, MD, associate professor and director of the Lymphoma Program at the University of Kansas Cancer Center, discussed the urgent need to bridge the gap between academic centers and community practices. He explored the logistical and emotional hurdles of the referral process—from managing caregiver burden and proximity requirements to the vital role of the "strident recommendation" from a community oncologist.

Beyond access, Dr Hoffmann outlined his practical clinical algorithm for managing Richter transformation when clinical trials are not immediately accessible.

Targeted Oncology: The Richter transformation remains one of the most daunting diagnoses in hematology. Given your recent work with the BRUIN (NCT03740529)¹ study, what are the red flags community oncologists should look for to catch this transformation early?

Marc S. Hoffmann, MD: The one piece I would say is that there really aren't any. These patients generally come in sick, so trying to get some kind of early detection is usually not going to be helpful. If you have a patient with chronic lymphocytic leukemia (CLL), particularly somebody with higher risk features who has received multiple lines of therapy, if they're coming in with new and concerning symptoms, I would work them up promptly. The biggest thing you can do is make sure that you're getting aggressive with their workup early on with imaging and lymph node biopsies.

What is your practical algorithm for managing these patients when clinical trials aren't immediately accessible?

My strongest recommendation in this population is to refer them to a transplant center, preferably one with a high-volume CLL program as well. In general, these patients benefit from some sort of cellular therapy, whether it be CAR T or allogenic stem cell transplantation. The window for transplantation can regrettably be somewhat short.

I generally do not give chemoimmunotherapy without targeted treatments as salvage. There was a paper that Matthew Davids, [MD, MMSc, attending physician in the Division of Lymphoma at Dana-Farber Cancer Institute],² published 2 or 3 years ago looking at venetoclax [Venclexta] with dose adjusted R-EPOCH, [rituximab (Rituxan), etoposide, prednisone, vincristine (Oncovin), cyclophosphamide, and doxorubicin (Hydroxydaunorubicin)], and in a patient that maybe has never had venetoclax or has never had a BCL2 inhibitor, we will sometimes do that as the remission rates were quite impressive.

Pirtobrutinib [Jaypirca] is also useful, with high response rates around 60%, but the responses just aren't durable, which is what we've generally seen with single-agent targeted therapy in Richter transformation. The pirtobrutinib will help control symptoms, improve counts, and reduce lymph nodes, but it is not going to clear marrow disease or lead to durable remissions. So, in general, you're going to need something beyond just the pirtobrutinib alone, with my preference being to add T-cell redirecting therapy with either CAR T or bispecifics

From a CAR T standpoint, we do have data on utilization of pirtobrutinib with CAR T in the relapsed CLL population that I think is applicable in Richter transformation as well.  These data were recently presented at ASH in December, and the durable response rates appear to be quite impressive. Additionally, there are some small series with epcoritamab [Epkinly] and I have found that the combination of epcoritamab with pirtobrutinib can be effective in managing Richter transformation.

However, and referencing back to my initial comments, I do strongly believe that current data suggest that patients with Richter transformation have the highest likelihood of cure with allogenic stem cell transplantation.  The above strategies can be used to get them into remission and prepare them for transplant, but generally we will transplant our Richter transformation patients, provided that they are candidates for transplant.

REFERENCES

1.A study of oral LOXO-305 in patients with previously treated CLL/SLL or NHL. ClinicalTrials.gov. Updated January 27, 2026. Accessed February 10, 2026. https://clinicaltrials.gov/study/NCT03740529

2.Davids M, Rogers K, Tyekucheva S, et al. Venetoclax plus dose-adjusted R-EPOCH for Richter syndrome. Blood. 2022 Feb 3;139(5):686-689. doi: 10.1182/blood.2021011386