Transformation of Richter's Transformation Treatment to combination targeted therapy - tislelizumab +zanubrutinib (ASH 2023)

[AussieNeil]

Richter's Transformation treatments are typically fixed term R-CHOP*, or modifications of that chemoimmunity therapy. So it's encouraging to hear that "In a phase 2 trial, anti-PD-1 inibitor tislelizumab + next gen BTK inhibitor zanubrutinib had an overall response rate of 58.3% in patients with Richter's transformation"

Here's the paper from German CLL study group authors at the University of Cologne

nature.com/articles/s41591-...

*R-CHOP is a combination of;

R = Rituximab, an anti-CD20 monoclonal antibody, the 'R' in FCR, BR, VR, etc

C = Cyclophosphamide, an alkylating agent, the 'C' in FCR

H = Doxorubicin Hydrochloride (Hydroxydaunomycin), an anthracycline

O = Vincristine Sulfate (Oncovin), an antimicrotubule agent used in the treatment of many different types of cancer

P = Prednisone, a corticosteroid

Interestingly, Vincristine is derived from the Madagascar Periwinkle and was initially investigated for the treatment of diabetes, when it was found that it lowered white cell counts.

jic.ac.uk/blog/vinblastine-... It's also known for its cardiotoxicity.

Neil

[CLLerinOz Administrator]

It’s so good to see such positive advances being made in the treatment of Richter’s Transformation with novel agents.

Commenting on this paper on social media today, lead author of the study, Othman Al-Sawaf, said, “Detailed translational studies to identify predictors of response and survival are ongoing and we look forward to sharing those data soon!”. x.com/othman_al_sawaf/statu...

Dr Toby Eyre has also delivered a presentation about Richters at the 2023 ASH conference and a link to his abstract is included in the following post: healthunlocked.com/cllsuppo...

In that abstract, he details historically poorer outcomes that make this study published today look so encouraging by comparison.

” … novel agents have the potential to impact the natural RT disease course”. That would be a very good thing indeed.

CLLerinOz

[Walkingtall62]

Hi, thanks for explaining what RCHOP is. Research is never ending. Take care

[Smakwater]

Although research is showing promising advances, from my view efficacy and endpoint measures are still pretty grimm. I hope the trend in advancing efficacy and durability continue exponentially.

Tolerability and side effect profiles are a bit rough as well.

Richters is an area of research that needs a knock it out of the park moment!

Thanks for some encouraging insight.

JM