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Anti-CD38 antibody therapy for patients with relapsed/refractory multiple myeloma: differential mechanisms of action and recent clinical trial outcomes
X. Leleu, T. Martin, K. Weisel, F. Schjesvold, S. Iida, F. Malavasi, S. Manier, . Chang-Ki Min, EM. Ocio, C. Pawlyn, A. Perrot, H. Quach, J. Richter, I. Spicka, K. Yong, PG. Richardson
Jazyk angličtina Země Německo
Typ dokumentu časopisecké články, přehledy
NLK
ProQuest Central
od 1997-03-01 do Před 1 rokem
Medline Complete (EBSCOhost)
od 2000-01-01 do Před 1 rokem
Nursing & Allied Health Database (ProQuest)
od 1997-03-01 do Před 1 rokem
Health & Medicine (ProQuest)
od 1997-03-01 do Před 1 rokem
- MeSH
- antigeny CD38 MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- mnohočetný myelom * terapie MeSH
- nádorové mikroprostředí MeSH
- protinádorové látky imunologicky aktivní * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
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.
Clinical Haematology Service St Vincent's Hospital University of Melbourne Melbourne Australia
Department of Haematology University College Hospitals NHS Foundation Trust London UK
Department of Hematology and Oncology Nagoya City University Nagoya Japan
Department of Hematology CHU Universite de Lille Lille France
Department of Hematology Institut Universitaire du Cancer de Toulouse Toulouse France
Department of Medical Oncology Dana Farber Cancer Institute Boston MA USA
Department of Medicine University of California at San Francisco San Francisco CA USA
Division of Cancer Therapeutics The Institute of Cancer Research London UK
Division of Hematology and Medical Oncology Tisch Cancer Institute Mount Sinai New York NY USA
Hospital Universitario Marqués de Valdecilla Universidad de Cantabria Santander Spain
Service d'Hématologie Et Thérapie Cellulaire CHU and CIC Inserm 1402 Poitiers Cedex France
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- $a 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.
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