Piers Blombery

CAR+ T-Cell Lymphoma after Cilta-cel Therapy for Relapsed or Refractory Myeloma | NEJM We describe two patients in whom malignant monoclonal T-cell lymphoproliferation developed after administration of chimeric antigen receptor (CAR) T-cell therapy with ciltacabtagene autoleucel (cil...

Two patients with refractory myeloma who had excellent antitumor responses to cilta-cel CAR T-cell therapy later had T-cell lymphomas that contained the lentivirus construct used to generate the CAR T-cell product. Brief Report on the CARTITUDE-4 trial: nej.md/4gA6G27

#MedSky #Hematology

CD4+ T-Cell Lymphoma Harboring a Chimeric Antigen Receptor Integration in TP53 | NEJM Malignant T-cell transformation after chimeric antigen receptor (CAR) T-cell therapy has been described, but the contribution of CAR integration to oncogenesis is not clear. Here we report a case o...

A recent case report from MSKCC published in the NEJM describes the development of a CD4+ T-cell lymphoma in a patient with multiple myeloma following B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy.

www.nejm.org/doi/full/10....

CD4+ T-Cell Lymphoma Harboring a Chimeric Antigen Receptor Integration in TP53 | NEJM Malignant T-cell transformation after chimeric antigen receptor (CAR) T-cell therapy has been described, but the contribution of CAR integration to oncogenesis is not clear. Here we report a case o...

A woman with multiply relapsed multiple myeloma had complete remission with cilta-cel, but a low-grade T-cell lymphoma soon developed in the GI tract that contained an insertion of the CAR construct disrupting expression of p53. Read the Brief Report: nej.md/40Yq3gO

#MedSky #Oncology

Attempt at putting what we know about #BTK resistance mutations into one figure..

Beware inducing cross-resistant L528Wmuts pre ncBTKi.

#hemesky #hematology #lymsm #hemepath #NGS

pubmed.ncbi.nlm.nih.gov/39808800/

Pediatric Myeloid Neoplasms With UBTF Tandem Duplications:... : The American Journal of Surgical Pathology e of AML. To further our understanding of myeloid neoplasms with UBTF-TD, we analyzed clinical, morphologic, and immunophenotypic characteristics of 27 pediatric patients with UBTF-TD-positive myeloid...

Make sure you are testing for UBTF-TDs in paed MDS/AML (and adult MDS/AML!).
Morphological/immunophenotypic clues = dysplasia in paed AML, CD34/CD117 dim
Molecular clues = FLT3mut/WT1mut
Menin inhibition as potential therapeutic modality.
#hemesky #hemepath

journals.lww.com/ajsp/fulltex...

Genomic mechanisms associated with resistance to PDL1-blockade in a patient with mantle cell lymphoma Published in Leukemia & Lymphoma (Ahead of Print, 2024)

CD274 3’UTR deletion and genomically hardwired #PDL1 over expression as an adaptive survival mechanism to #atezolizumab.. ?specific mechanism to targeting the tumour side of the immune synapse #hemesky #hemepath

doi.org/10.1080/1042...

What a joy it is to hear our very own Sant-Ryan Pasricha presenting Best of #ASH24. Who else could personalise this so much and use a picture of the hallowed ground of the @MCG (Melbourne Cricket Ground) to such good effect? Go Santa!

Therapy related myeloid neoplasm post CART in DLBCL arises from TP53 clones identifiable preCART… but high baseline incidence of TP53/PPM1D CH preCART.. so the challenge is identifying those with clones that will progress - Zhi Han Yeoh from @petermaccc.bsky.social. #ASH24 #hemepath #hemesky #lymsm

Very interesting R-CHOP+X session (or Pola-R-CHP+X..) in DLBCL. 3/6 presentations in the session with data presented on ctDNA MRD!.. including the COALITION study (Adrian Minson/ @drmikedickinson.bsky.social. CtDNA helpful in resolving nature of EOT PET abnormalities #ASH24 #lymsm #hemesky #hemepath

Critical RW data, especially data re: better PFS for pola for non-GC in the post-CAR setting. Huge congratulations to Drs. Cliff and Russler-Germain for this tour de force, and for inviting us at @CULymphoma @CUHematology (and @JessicaAllenMD) to participate. #ASH24 #lymsm

Zoe McQuilten from Monash 🇦🇺presenting the final results of the Diaamond-AVA-first looking at hATG, CSA, and avatromboag. Similar results to eltrombopag seen. #ASH24 @ash-hematology.bsky.social

Dr. Jacoby from Washington University on intervening in AML based on mut clearance at 2.5% VAF across exome level in a variant agnostic way. Great to see this “fingerprint” MRD approach being used in trials.. lots of analogies to current lymphoma ctDNA space #hemepath #hemesky #leusm #lymsm #ASH24

Exciting to see the first results from the INTERCEPT platform study (PI Andrew Wei) expertly presented by Dr. Sun Loo from @petermaccc.bsky.social at #ASH24. Intervening with a molecularly rational approach at early #MRD relapse is feasible in AML and the results with revumenib are encouraging.

Dr. Ing Soo Tiong from @petermaccc.bsky.social presenting his excellent work at #ASH24 on how the remission clonal haematopoietic landscape is shaped by venetoclax in pts with AML. TP53 and BAX microclones! With a bit more sensitive sequencing tech we will find the nanoclones… #hemepath #hemesky

A great (in-person!) meeting of the MM-VCEP #ClinGen group today at #ASH24. Lots of exciting projects and milestones for the group on the horizon including making rules for new genes (SAMD9/SAMD9L/TERT/TERC..) as well as progress on our DDX41 curation rules. Stay tuned..

Loss of function TET2 germline variants.. potentially a lot more common than previously thought.. Well done to Sean Harrop presenting our work on this emerging immune dysregulatory syndrome in the germline BMF workshop at #ASH24 #hemepath #hemesky

Blood experts unite
Hmmm.. so what do we need now?
I know, pickleball..

#ASHaiku #ASH24

YouTube video by Marcin W ASH 2024 Friday Scientific Workshop on Germline Predisposition to Hematologic Malignancies and BMF

Looking forward to the Germline Predisposition FSW at #ASH24… (check out summary at link below!). For those attending - make sure you stay to hear Sean Harrop present our work on germline #TET2 variants and an emerging novel syndrome..
#hemesky #hemepath #hematology
youtu.be/UEKszF06k2Y

NGS variants prior to CAR #ASH24:
- 173 pts, 63% axi-cel
- 43% had CH prior to CAR: 54% DNMT3A, 26% TP53
- 6% developed MN: 3-yr cumulative incidence of 11% with death from LBCL as competing risk
- median time CAR to MN 25 mos
- CH➡️late thrombocytopenia after CAR #lymsm #bmtsm

Why are scientists so excited about genomics? - ABC listen Genomics explores the building blocks of human DNA, in the hopes of uncovering patterns that can lead to lifesaving medical discoveries.

We recently joined forces with the University of Melbourne to create the Collaborative Centre for Genomic Cancer Medicine.

It's Director Prof Sean Grimmond and A/Prof David Westerman joined ABC Melbourne to talk about the new centre's mission and future of #genomicmedicine.

A fascinating listen!

✋!