Sequencing of Novel Therapies for Mantle Cell Lymphoma

Romancik, Jason T.; Cohen, Jonathon B.

doi:10.1007/s11864-021-00907-3

Cited by 5 publications

(5 citation statements)

References 89 publications

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“…1B ). Aside from chemoimmunotherapy, other options for bridging therapy include lenalidomide or venetoclax-based regimens [ 73 , 74 ], radiation, or corticosteroids. In patients who previously received a covalent BTKi, treatment with a non-covalent BTKi may be considered if approved.…”

Section: Expert Opinionmentioning

confidence: 99%

BTK Inhibitors and CAR T-Cell Therapy in Treating Mantle Cell Lymphoma—Finding a Dancing Partner

et al. 2022

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Purpose of Review This review focuses on the feasibility of combining Bruton’s tyrosine kinase (BTK) inhibitors (BTKis) with chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL). Potential scenarios for combination treatment with these agents are presented. Recent Findings BTKis and CAR T-cell therapy have revolutionized the treatment paradigm for R/R MCL. Ibrutinib, acalabrutinib, and zanubrutinib are covalent irreversible BTKis approved for R/R MCL. Brexucabtagene autoleucel was the first CAR T-cell therapy approved for R/R MCL based on findings from the ZUMA-2 trial. There is evidence to suggest that combination treatment with BTKis and CAR T-cell therapy may improve CAR T-cell efficacy. Summary As BTKis and CAR T-cell therapy become mainstays in R/R MCL therapy, combination treatment strategies should be evaluated for their potential benefit in R/R MCL.

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Section: Expert Opinionmentioning

confidence: 99%

BTK Inhibitors and CAR T-Cell Therapy in Treating Mantle Cell Lymphoma—Finding a Dancing Partner

et al. 2022

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“…Patienten mit R/R MCL nach Exposition gegenüber einem kovalenten BTKi sollten für eine CAR-T-Zell-Therapie in Betracht gezogen werden (Abb 1B). Neben der Chemoimmuntherapie gibt es weitere Optionen für eine Überbrückungstherapie wie Lenalidomid- oder Venetoclax-basierte Therapien [73, 74], Bestrahlung oder Kortikosteroide. Bei Patienten, die zuvor einen kovalenten BTKi erhalten haben, kann eine Behandlung mit einem ggf.…”

Section: Einführungunclassified

BTK-Inhibitoren und CAR-T-Zell-Therapie bei der Behandlung des Mantelzelllymphoms – einen Tanzpartner finden

Muñoz

Wang

Jain³

et al. 2022

Kompass Onkol

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Diese Übersichtsarbeit konzentriert sich auf die Machbarkeit der Kombination von Bruton-Tyrosinkinase (BTK)-Inhibitoren (BTKi) mit einer chimären Antigenrezeptor (CAR)-T-Zell-Therapie bei Patienten mit rezidiviertem oder refraktärem (R/R) Mantelzelllymphom (MCL). Es werden mögliche Szenarien für eine Kombinationsbehandlung mit diesen Wirkstoffen vorgestellt. <b>Jüngste Erkenntnisse:</b> BTKi und die CAR-T-Zell-Therapie haben das Behandlungsparadigma für R/R MCL revolutioniert. Ibrutinib, Acalabrutinib und Zanubrutinib sind kovalente irreversible BTKi, die für R/R MCL zugelassen sind. Brexucabtagen-Autoleucel war die erste CAR-T-Zell-Therapie, die in Folge der Ergebnisse der ZUMA-2-Studie für R/R MCL zugelassen wurde. Es gibt Hinweise darauf, dass eine kombinierte Behandlung mit BTKi und einer CAR-T-Zell-Therapie die Wirksamkeit der CAR-T-Zellen verbessern kann. <b>Zusammenfassung:</b> Da BTKi und CAR-T-Zell-Therapien in der R/R-MCL-Therapie immer wichtiger werden, sollten Kombinationsbehandlungsstrategien für R/R-MCL auf ihren potenziellen Nutzen untersucht werden.

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“…For the latter, it is combined with a hypomethylating agent (either azacitidine or decitabine) or low-dose chemotherapy (cytarabine) ( 12 – 14 ). Venetoclax is also sometimes used off-label as a bridge-to-transplant or bridge-to-CAR T cell therapy in ALL and B cell NHL ( 15 , 16 ).…”

Section: Introductionmentioning

confidence: 99%

Comparative analysis of Bcl-2 family protein overexpression in CAR T cells alone and in combination with BH3 mimetics

Korell,

Olson,

Salas-Benito

et al. 2024

Sci. Transl. Med.

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Approximately 50% of patients with hematologic malignancies relapse after chimeric antigen receptor (CAR) T cell treatment; mechanisms of failure include loss of CAR T persistence and tumor resistance to apoptosis. We hypothesized that both of these challenges could potentially be overcome by overexpressing one or more of the Bcl-2 family proteins in CAR T cells to reduce their susceptibility to apoptosis, both alone and in the presence of BH3 mimetics, which can be used to activate apoptotic machinery in malignant cells. We comprehensively investigated overexpression of different Bcl-2 family proteins in CAR T cells with different signaling domains as well as in different tumor types. We found that Bcl-xL and Bcl-2 overexpression in CAR T cells bearing a 4-1BB costimulatory domain resulted in increased expansion and antitumor activity, reduced exhaustion, and decreased apoptotic priming. In addition, CAR T cells expressing either Bcl-xL or a venetoclax-resistant Bcl-2 variant led to enhanced antitumor efficacy and survival in murine xenograft models of lymphoma and leukemia in the presence or absence of the BH3 mimetic venetoclax, a clinically approved BH3 mimetic. In this setting, Bcl-xL overexpression had stronger effects than overexpression of Bcl-2 or the Bcl-2(G101V) variant. These findings suggest that CAR T cells could be optimally engineered by overexpressing Bcl-xL to enhance their persistence while opening a therapeutic window for combination with BH3 mimetics to prime tumors for apoptosis.

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Sequencing of Novel Therapies for Mantle Cell Lymphoma

Cited by 5 publications

References 89 publications

BTK Inhibitors and CAR T-Cell Therapy in Treating Mantle Cell Lymphoma—Finding a Dancing Partner

BTK Inhibitors and CAR T-Cell Therapy in Treating Mantle Cell Lymphoma—Finding a Dancing Partner

BTK-Inhibitoren und CAR-T-Zell-Therapie bei der Behandlung des Mantelzelllymphoms – einen Tanzpartner finden

Comparative analysis of Bcl-2 family protein overexpression in CAR T cells alone and in combination with BH3 mimetics

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