Rahul Banerjee: Fatal case of enteric T-cell lymphoma following cilta-cel CAR integration into the TP53 locus
Rahul Banerjee, Assistant professor at Fred Hutchinson Cancer Center at the University of Washington, shared on X:
“Sobering but important work in NEJM by Michael Scordo, Saad Z. Usmani et al: fatal case of enteric T-cell lymphoma following cilta-cel (MM CAR-T) CAR integration into the TP53 locus. One of few papers that informs clinical discussions the moment it comes out. My two takeaways:
Authors: Karlo Perica, Nayan Jain, Michael Scordo, Ruchi Patel, Ozgur Can Eren, Utsav Patel, Gunes Gundem, Dylan Domenico, Sneha Mitra, Nicholas D. Socci, John K. Everett, Aoife M. Roche, Angelina Petrichenko, Gunjan L. Shah, Maria E. Arcila, Laetitia Borsu, Jae H. Park, Steven M. Horwitz, Sergio A. Giralt, Ahmet Dogan, Christina Leslie, Elli Papaemmanuil, Frederic D. Bushman, Saad Z. Usmani, Michel Sadelain, and Sham Mailankody
This is no longer just a theoretical risk we discuss with patients – now a real (but of course incredibly rare) risk. None of our commercial CAR-Ts currently use safety switches or aim for integration into genomic safe harbors… … I’m definitely more interested in them now!
Authors: Ashlesha OdakHan YuanJudith FeuchtVito Adrian CantuJorge Mansilla-SotoFriederike KogelJustin EyquemJohn EverettFrederic D. BushmanChristina S. LeslieMichel Sadelain
On flip side, not all diarrhea after Multiple myeloma CAR-T is enteric lymphoma! We’ve reported in Blood Cancer Journal about polyclonal T-cell infiltration causing IEC-associated enterocolitis – use inflix, not steroids. But ruling out enteric lymphoma is critical.
Authors: Gliceida Galarza Fortuna, Rahul Banerjee, Constanza Savid-Frontera, Jinming Song, Carlos M. Morán-Segura, Jonathan V. Nguyen, Lazaros Lekakis, Sebastian Fernandez-Pol, Annie N. Samraj, Kikkeri N. Naresh, Mariola Vazquez-Martinez, Rachid C. Baz, Jay Y. Spiegel, Lekha Mikkilineni, John M. Gubatan, Surbhi Sidana, Andre de Menezes Silva Corraes, Nilesh M. Kalariya, Krina K. Patel, Kevin G. Shim, Rafael Fonseca, Christopher Ferreri, Peter M. Voorhees, Shambavi Richard, Cesar Rodriguez Valdes, Sireesha Asoori, Jeffrey L. Wolf, Andrew J. Cowan, Douglas W. Sborov, Frederick L. Locke, Yi Lin, Yinghong Wang and Doris K. Hansen
Big unanswered question – is this risk unique to cilta-cel, later lines of therapy versus early lines, or to myeloma? My guess: probably not. Benefits of CAR-T still vastly outweigh risks for most, but I’ll be changing this part of my discussions with patients immediately.”
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