Maximilian Merz, Associate Attending Physician at Memorial Sloan Kettering Cancer Center, shared a post on LinkedIn, about a recent article he and his colleagues co-authored, adding:
“What’s the secret sauce behind Cilta-cel.
I am very proud to share our answer to that question published today in Cancer Cell by Cell Press.
When I started treating myeloma patients with T-cell engaging therapies, my immunology world was in order: activation, expansion and persistence of cytotoxic CD8 T cells was associated with responses after Idecel and bispecific antibodies in relapsed myeloma.
While I was amazed by the responses after Ciltacel, I was even more surprised by the first flow studies from our lab showing robust expansion of CD4-positive CAR T cells after Cilta-cel.
Our longitudinal single-cell multi-omic atlas now shows that response, but also side effects are linked to expansion of eomesodermin- and granulosyin-expressing, cytotoxic CD4 CAR T cells.
Other key findings include
- the pre-existing TCR repertoire and its dynamics are important to predict outcomes and side effects
- sBCMA is a great marker to predict and monitor response
- plasmacytoid dendritic cells (pDCs) are the cells with the highest BCMA-expression outside the B-cell compartment
- BCMA-directed therapies eradicate hashtag#BPDCN cell lines offering a new treatment for patients with this rare disease
Major clinical takeaways
- monitor CAR T cells to manage side effects!
- use CAR T cells like any other cellular therapy in MM, as consolidation and not to induce remissions
- optimize response prior to CAR T with effective holding/bridging therapies
- monitor B-cell and T-cell recovery to time preventive measures (IVIGs, vaccinations, bactrim/acic)
This work would not have been possible without the generous support from the Paula and Rodger Riney Foundation, International Myeloma Society, Johnson and Johnson, SpringWorks Therapeutics, Fundación Josep Carreras, German Research Foundation and the European Commission.
Building on this work, we will now try to answer some of the most pertinent questions connected to CAR T cell therapies: Deciphering the biology and finding treatments for IEC-colitis, delayed neurotoxicity and CAR-positive T cell lymphomas!
So lot’s of work to do for our amazing group from University Hospital Leipzig Public Law Foundation, Memorial Sloan Kettering Cancer Center, Universitätsklinikum Carl Gustav Carus Dresden, Singleron Biotechnologies, Utrecht University, University Hospital of Würzburg, and ScaDS.AI Dresden/Leipzig.
Big shout out to the amazing first authors: Michael Rade, David Fandrei, and Markus Kreuz.”
Title: A longitudinal single-cell atlas to predict outcome and toxicity after BCMA-directed CAR T cell therapy in multiple myeloma
Authors: Michael Rade, David Fandrei, Markus Kreuz, Sabine Seiffert, Anja Grahnert, Maik Friedrich, Thomas Wiemers, Patrick Born, Luise Fischer, Heike Weidner, Lorenz C. Hofbauer, Ronny Baber, Song Yau Wang, Enrica Bach, Sandra Hoffmann, Jonathan Scolnick, Mirco Friedrich, Farid Keramati, Peter Brazda, Zsolt Sebestyen, Jürgen Kuball, Miriam Alb, Lukas Scheller, Michael Hudecek, Hermann Einsele, Klaus H. Metzeler, Marco Herling, Carmen Diana Herling, Madlen Jentzsch, Georg-Nikolaus Franke, Andreas Boldt, Ulrike Köhl, Uwe Platzbecker, Vladan Vucinic, Kristin Reiche, Maximilian Merz
Read the Full Article on Cancer Cell by Cell Press
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