Treatment of Richter's syndrome - ASH 2022 Education Program

[CLLerinOz]

This year's American Society of Hematology (ASH) annual conference is now underway and the ASH Education Program, Volume 2022, Issue 1 booklet that was published on 9 December 2022 is now available at: ashpublications.org/hematol...

It contains three review articles from sessions about CLL. This post is about one of those three articles: "Treatment of Richter's syndrome" by Philip A. Thompson, The University of Texas MD Anderson Cancer Center, and Tanya Siddiqi, City of Hope National Medical Center.

"ABSTRACT: Richter's syndrome (RS) is an aggressive histologic transformation of chronic lymphocytic leukemia (CLL), most commonly to diffuse large B-cell lymphoma (DLBCL). Outcomes are generally poor, with complete remission (CR) rates of only about 20% and less than 20% long-term survival with chemoimmunotherapy (CIT). RS is biologically heterogeneous, and in 80% of patients with CLL who develop DLBCL, the disease is clonally related to the CLL. Clonally unrelated cases are genetically and immunologically distinct from clonally related DLBCL-RS, have more favorable responses to CIT, and are best treated as de novo DLBCL. Relatively favorable outcomes with CIT are also seen in patients who have never previously received treatment for CLL and who lack TP53 mutation or deletion. For the remaining patients, treatment on a clinical trial is optimal. Fortunately, numerous agents are now in clinical development that show encouraging results. Here we review clinical data for some of the most promising approaches. DLBCL-RS tumor cells frequently express programmed cell death 1 protein (PD-1), and several studies have demonstrated activity for PD-1 inhibitors, especially in combination with ibrutinib. The BCL2 inhibitor venetoclax in combination with R-EPOCH CIT achieved CR in 50% of patients, and a study of venetoclax–R-CHOP is ongoing. The noncovalent Bruton's tyrosine kinase inhibitor pirtobrutinib has achieved responses in approximately two-thirds of heavily pretreated patients and, given its favorable toxicity profile, appears ideally suited to combining with other active agents. Finally, we review available data for bispecific antibodies, antibody-drug conjugates, and chimeric antigen receptor T-cell therapy, which, after revolutionizing the treatment of DLBCL, are now being evaluated in RS."

In addition to a case study, this article discusses:

Diagnosis of RS

PET/CT and Biopsy

Risk factors, molecular pathogenesis, and prognosis

Prognostic features

Variants

CIT in the treatment of DLBCL-RS

Hematopoietic progenitor cell transplantation in DLBCL-RS

Novel approaches to DLBCL-RS treatment

Small-molecule targeted agents

Antibody-based therapy

Chimeric antigen receptor T-cell and chimeric antigen receptor natural killer cell therapy

Trials of interest

How we treat

Philip A. Thompson, Tanya Siddiqi; Treatment of Richter's syndrome. Hematology Am Soc Hematol Educ Program 2022; 2022 (1): 329–336. doi: doi.org/10.1182/hematology....

[Pippety]

This is an awesome paper, thanks for posting!

[CLLerinOz Administrator in reply to Pippety]

👍

[Pippety]

CLLerinOz, this is another good paper from ASH 2022 regarding Richters: ash.confex.com/ash/2022/web...

[CLLerinOz Administrator in reply to Pippety]

Thanks, Pippety. Some other relevant abstracts are also included in a separate post about this year's ASH conference:

healthunlocked.com/cllsuppo...

You will also see some other older posts that have been allocated the Richter's tag if you select "Richter's" from our Topics list (which you'll see to the right of your screen if you're on a PC or laptop or at the bottom of your screen if you scroll down on a phone). There may be others that haven't been allocated a tag by their author and you could find them using the Post search function for our community.