The preclinical discovery and clinical development of ciltacabtagene autoleucel (Cilta-cel) for the treatment of multiple myeloma

INTRODUCTION: Despite remarkable therapeutic advances over the last two decades, which have resulted in dramatic improvements in patient survival, multiple myeloma (MM) is still considered an incurable disease. Therefore, there is a high need for new treatment strategies. Genetically engineered/redirected chimeric antigen receptor (CAR) T cells may represent the most compelling modality of immunotherapy for cancer treatment in general, and MM in particular. Indeed, unprecedented response rates have led to the recent approvals of the first two BCMA-targeted CAR T cell products idecabtagene-vicleucel ('Ide-cel') and ciltacabtagene-autoleucel ('Cilta-Cel') for the treatment of heavily pretreated MM patients. In addition, both are emerging as a new standard-of-care also in earlier lines of therapy.

AREAS COVERED: This article briefly reviews the history of the preclinical development of CAR T cells, with a particular focus on Cilta-cel. Moreover, it summarizes the newest clinical data on Cilta-cel and discusses strategies to further improve its activity and reduce its toxicity.

EXPERT OPINION: Modern next-generation immunotherapy is continuously transforming the MM treatment landscape. Despite several caveats of CAR T cell therapy, including its toxicity, costs, and limited access, prolonged disease-free survival and potential cure of MM are finally within reach.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:19

Enthalten in:

Expert opinion on drug discovery - 19(2024), 4 vom: 16. März, Seite 377-391

Sprache:

Englisch

Beteiligte Personen:

Strassl, Irene [VerfasserIn]
Podar, Klaus [VerfasserIn]

Links:

Volltext

Themen:

B cell maturation antigen (BCMA)
Cytokine release syndrome (CRS)
Immune effector cell-associated neurotoxicity syndrome (ICANS)
Journal Article
Multiple myeloma (MM)
Second-generation CAR T cells

Anmerkungen:

Date Completed 20.03.2024

Date Revised 20.03.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1080/17460441.2024.2319672

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM368598209