New International Consensus Statement on Diagnosis, Evaluation, and Research of Richter Transformation: the ERIC Recommendations

[CLLerinOz]

An important review article about Richter Transformation was published in the journal Blood on 16 April 2025.

"Key Points

Investigation of RT tissue is required for appropriate diagnosis and to understand the pathobiology of this poor-risk lymphoma subtype.

Due to the poor prognosis of RT with conventional chemoimmunotherapy, participation in clinical trials should be prioritized.

Abstract

Richter transformation (RT) is defined as an aggressive lymphoma emerging in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL). Despite novel therapeutics developed in CLL, RT is associated with poor outcomes. In light of recent progress regarding the diagnostic procedures and therapeutic concepts of RT, an international group of experts, under the coordination of the European Research Initiative on CLL (ERIC), has developed consensus recommendations for clinical procedures and future research on this disease.

Patients with RT typically present with a rapid clinical decline, worsening B-symptoms, elevated LDH, and/or rapidly enlarging lymphadenopathy.

Workup should include a PET-CT for patients with suspected RT. An excisional biopsy should be taken from an accessible lesion, preferably with the highest FDG avidity, and analyzed for the presence of aggressive lymphoma.

The molecular relationship to the original CLL clone(s) should be defined.

As no effective standard treatment for RT exists, patients should be treated in a clinical trial.

Response of both RT and CLL should be assessed at an early time point, and survival endpoints should be prioritized in trial design.

We hope that these recommendations can help to harmonize clinical and translational research and improve outcomes for patients with RT."

See the full pdf of the review article for more details:

Adam S Kittai, Monia Marchetti, Othman Al-Sawaf, Ohad Benjamini, Alexey V Danilov, Matthew S. Davids, Barbara F. Eichhorst, Toby A. Eyre, Anna Maria Frustaci, Michael J Hallek, Paul Joseph Hampel, Yair Herishanu, Rodney John Hicks, Arnon P. Kater, Rebecca L. King, José-Ignacio Ignacio Martín-Subero, Carolyn Owen, Erin M. Parry, Maurilio Ponzoni, Davide Rossi, Tanya Siddiqi, Stephan Stilgenbauer, Constantine S. Tam, Elisa ten Hacken, Philip A Thompson, William G. Wierda, Gianluca Gaidano, Jennifer A. Woyach, Paolo Ghia; International Consensus Statement on Diagnosis, Evaluation, and Research of Richter Transformation: the ERIC Recommendations. Blood 2025; blood.2024028064. doi: doi.org/10.1182/blood.20240...

It covers:

Section 1 - Epidemiology, Diagnosis, and Prognosis of Richter Transformation

Epidemiology & Prevalence

Risk of RT

When to suspect RT

Role of imaging (PET-CT)

Appropriate Biopsy

Appropriate determination of clonal relationship

Prognosis

Section 2 – Baseline Laboratory Testing, Prognostication, and Staging

Prognostication

Laboratory Testing - Importance of NGS and molecular testing and Role for additional molecular or genetic testing in RT

Staging/Pre-treatment Assessment

Section 3 – Clinical Trial Recommendations

"Over the past 20 years, RT has been largely excluded from trials testing novel therapies for both CLL and DLBCL. As the prognosis of RT remains poor, it is essential to conduct prospective clinical trials specifically dedicated to this disease either by academic investigators, the pharmaceutical industry or cooperative groups. We provide recommendations for trial development in RT"

Eligibility criteria for clinical trials

Endpoints of clinical trials

Biobanking and exploratory endpoints

Response assessments

Toxicity Assessment

Sample size planning

Section 4 – Discussion: Future Directions and Exploratory Endpoints

Conclusions:

"Considering recent advances in understanding the biology of RT, meaningful progress by plausible pathology mechanistic-based therapies now seems possible. Further laboratory investigations using primary longitudinal samples, molecular analyses and novel in vivo models are needed to develop rational therapeutic strategies. Current clinical research should incorporate CLL therapies for RT, and clinical trials should monitor the response of both the aggressive lymphoma and the CLL. Through collaborative basic, translational, and clinical research, improvement in outcomes for patients with RT may be achieved."

CLLerinOz (my emphasis)

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[Sushibruno]

IT has been said that richters is curable but then again it has been said that it has a poor outcome. Which one is it? This possibility is always in the back of my mind and it terrifies the living soul out of me. I’m sorry I’m just being honest this is so scary.

[CLLerinOz Administrator in reply to Sushibruno]

Both can be true.

Although RT (Richter Transformation) can have a poor outcome, that's not inevitable and new knowledge about the mechanisms driving it and the availability of newer therapies mean RT can be curable.

Patient Power recently posted the story of Catherine Ferguson, a Richter patient, who described it this way:

"I think it was like a month into treatment when I looked at one of the reports that said something about Richter's transformation, and I was like, oh my god, I'm going to die because everybody thinks Richter's…it's a really bad thing, and it still is to this day. It's an unmet need in the CLL world, but not everybody has to die from Richter’s and not everybody has to do poorly with Richter’s. And so that also, getting through that whole episode, I have been in complete remission from the Richter's and the Hodgkin's since I finished chemo in August of 2018, and I just recently had a bone marrow biopsy, and there's no evidence of any Hodgkin's in my bone marrow." patientpower.info/video/chr...

The tone of the consensus statement is cautiously optimistic, I'd say, so take heart. My grandmother used to tell me, "Don't trouble trouble 'til trouble troubles you" and I try to remember that whenever I start overthinking what might be.

CLLerinOz

[Sushibruno in reply to CLLerinOz]

“Don’t trouble trouble ‘til trouble troubles you” I will think about this quote whenever I start overthinking what might be. Thank you CllerinOz🤗.

[Fowey2009 in reply to CLLerinOz]

Hodgkins richters (referred to in the quote above) has better outcomes than DLBCL (and is far less frequent than DLBCL). However even DLBCL is now getting better outcomes.

Having been through richters (Hodgkins) with my husband, we are determined to enjoy each day at a time. Since he was seriously ill just over two years ago, we have had some wonderful times and will be going on a 3 week walking holiday next month.

Absolutely agree with don’t trouble trouble!

Beryl

[AussieNeil Partner Administrator in reply to Sushibruno]

Both can be true Lydia - we have quite a few members who have beaten Richter's Transformation. RT treatment also knocks back CLL, but unfortunately doesn't cure it. Thankfully we now better know the Richter's risk factors and incidence. When I was diagnosed with CLL back in 2009, the risk was commonly reported as around 10% or higher. For most of us, the risk would now considered to be under 2%.

Ironically, a significant challenge with conducting research into how to improve the likelihood of a good outcome from RT treatment, is that because RT is rare, researchers are finding it difficult to get enrolments in clinical trials. This means that there's a good likelihood of having a clinical trial available for anyone who develops RT. Clinical trials for cancer are set up with the expectation that those in clinical trials on new treatments will do at least as well as those on established treatments.

Also, we need to keep in mind that for those of us coming off BTKi treatments, (the 'brutinibs'), what's thought to be RT, is often a tumor flare that looks very much like RT, termed "pseudo Richter's". Some of us have even been mistakenly treated for RT, when just resuming BTKi therapy would again bring our CLL under control. That's why anyone thinking they have developed RT after stopping acalabrutinib, ibrutinib, pirtobrutinib, zanubrutinib, etc., should have their suspicious node biopsy evaluated by a pathologist associated with a well recognised CLL treatment center.

Neil

[Sushibruno in reply to AussieNeil]

Thank you for the continuous education you give us on these difficult topics for many of us Neil. Appreciate it very much.

[BigfootT]

Great post and good to see the consensus. I just went through this protocol at Mayo in February although they could only core biopsy my highest node (took 10 samples) because of it's difficult location next to my kidney ureter and renal vein. Thankfully it was just SLL.

Bigfoot