Anti-CD38 antibody therapy for patients with relapsed/refractory multiple myeloma: differential mechanisms of action and recent clinical trial outcomes.
CD38
Monoclonal antibody
Myeloma
Therapy
Journal
Annals of hematology
ISSN: 1432-0584
Titre abrégé: Ann Hematol
Pays: Germany
ID NLM: 9107334
Informations de publication
Date de publication:
Oct 2022
Oct 2022
Historique:
received:
26
01
2022
accepted:
02
07
2022
pubmed:
10
8
2022
medline:
14
9
2022
entrez:
9
8
2022
Statut:
ppublish
Résumé
CD38 is a transmembrane glycoprotein that functions both as a receptor and an ectoenzyme, playing key roles in the regulation of calcium signaling and migration of immune cells to tumor microenvironments. High expression on multiple myeloma (MM) cells and limited expression on normal cells makes CD38 an ideal target for the treatment of MM patients. Two monoclonal antibodies directed at CD38, isatuximab and daratumumab, are available for use in patients with relapsed and/or refractory MM (RRMM); daratumumab is also approved in newly diagnosed MM and light-chain amyloidosis. Clinical experience has shown that anti-CD38 antibody therapy is transforming treatment of MM owing to its anti-myeloma efficacy and manageable safety profile. Isatuximab and daratumumab possess similarities and differences in their mechanisms of action, likely imparted by their binding to distinct, non-overlapping epitopes on the CD38 molecule. In this review, we present the mechanistic properties of these two antibodies and outline available evidence on their abilities to induce adaptive immune responses and modulate the bone marrow niche in MM. Further, we discuss differences in regulatory labeling between these two agents and analyze recent key clinical trial results, including evidence in patients with underlying renal impairment and other poor prognostic factors. Finally, we describe the limited existing evidence for the use of isatuximab or daratumumab after disease progression on prior anti-CD38 mono- or combination therapy, highlighting the need for additional clinical evaluations to define optimal anti-CD38 antibody therapy selection and sequencing in RRMM.
Identifiants
pubmed: 35943588
doi: 10.1007/s00277-022-04917-5
pii: 10.1007/s00277-022-04917-5
pmc: PMC9463192
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
ADP-ribosyl Cyclase 1
EC 3.2.2.6
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2123-2137Informations de copyright
© 2022. The Author(s).
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