Thrilled to share our latest study on secondary myeloid malignancies after CAR-T cell therapy led by Dr Francesca Sillito .@uclh @drclaireroddie @Capt__Kirkwood @Haematologica .

RT @TheEBMT: There are plenty of reasons to join #ITCTC25 this September in 📍 Barcelona. 🏛️. It's time to plan your trip and explore the f….

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RT @alliancerm: This week, the European Union approved its second cell and gene therapy of 2025. Autolus Therapeutics announced that the….

RT @larsgjaerde: Come join us at the TCWP Educational Meeting in Dubrovnik on 1-3 October! Early Bird registration deadline on 28 July and….

RT @RahulBanerjeeMD: Clever title! By @RoloffGreg in @Haematologica editorial about SPM following CAR-T by @ARampotas @drclaireroddie et al….

RT @ARampotas: At @uclh, 10 cases of tMN were identified among 403 NHL patients receiving CAR-T (2.48% incidence). Median onset: Just ~7 mo….

Also read the very nice editorial by @RoloffGreg . “And her mother bare Chimera, in rage and flame, a creature mingled of diverse parts.” - Ovid, Metamorphoses (Book IX)

The potential benefit and curative potential of CAR-T cell therapy far outweighs the risk of secondary malignancies, but strategies to identify the ones who are most at risk are important for the safe delivery of this revolutionary therapy.

What now?.🔹 Screen high-risk patients for CHIP pre-CAR-T?.🔹 Monitor those with CHIP more closely post-infusion?.🔹 Consider earlier allo-SCT in those who develop tMN?.

Mechanistically, CAR-T may create a pro-inflammatory bone marrow niche favoring expansion of pre-leukemic clones.

Interestingly, ferritin and CRP (inflammatory markers) didn’t correlate with risk, but higher lymphocyte counts (and a trend for higher CRS grade) did, raising the question: does CAR-driven inflammation accelerate tMN?.

So who’s at risk?.Univariable analysis showed strong associations with:.🔺 Higher CAR-Hematotox (HT) score pre-CAR-T. 🔺 More prior lines of therapy. 🔺 Prior autologous transplant. 🔺 Peak lymphocyte count post-CAR-T (surrogate for CAR expansion).

Importantly, these mutations expanded or persisted post-CAR-T, suggesting CAR-T therapy may promote clonal progression in susceptible patients. However, one should take into account the burden of prior chemotherapy burden.

Genomic analysis revealed pre-existing CHIP in 4/7 tested patients before CAR-T. Common mutations included TP53, TET2, ASXL1, DNMT3A, and PPM1D—all known drivers of clonal evolution under stress.

What kinds of tMN?. AML: 2/10. MDS: 8/10 (often with poor-risk features like bi-allelic TP53 inactivation, monosomy 7, or complex karyotypes).

At @uclh, 10 cases of tMN were identified among 403 NHL patients receiving CAR-T (2.48% incidence). Median onset: Just ~7 months post-infusion. Outcomes were poor: median OS after tMN diagnosis was 8.1 months.

While CAR-T trials didn’t flag tMN as a major issue, real-world data suggests up to 6% of patients develop secondary cancers, often within months of infusion.

RT @iannisaifantis1: Good to see some good press from @TheEconomist on the impact of cancer basic+clinical research. #CancerResearch #Canc….

RT @TheElfLab: Honored to write this with @nsarellano9 and congratulations to dear friends @mkonople and @doctorpemm on such important and….