Elotuzumab monotherapy in patients with smouldering multiple myeloma: a phase 2 study.

Abstract

Smouldering multiple myeloma (SMM) is associated with increased risk of progression to multiple myeloma within 2 years, with no approved treatments. Elotuzumab has been shown to promote natural killer (NK) cell stimulation and antibody-dependent cellular cytotoxicity (ADCC) in vitro. CD56dim (CD56dim /CD16+ /CD3- /CD45+ ) NK cells represent the primary subset responsible for elotuzumab-induced ADCC. In this phase II, non-randomized study (NCT01441973), patients with SMM received elotuzumab 20 mg/kg intravenously (cycle 1: days 1, 8; monthly thereafter) or 10 mg/kg (cycles 1, 2: weekly; every 2 weeks thereafter). The primary endpoint was the relationship between baseline proportion of bone marrow-derived CD56dim NK cells and maximal M protein reduction; secondary endpoints included overall response rate (ORR) and progression-free survival (PFS). Fifteen patients received 20 mg/kg and 16 received 10 mg/kg; combined data arepresented. At database lock (DBL, September 2014), no association was found between baseline CD56dim NK cell proportion and maximal M protein reduction. With minimum 28 months' follow-up (DBL: January 2016), ORR (90% CI) was 10% (2·7-23·2) and 2-year PFS rate was 69% (52-81%). Upper respiratory tract infections occurred in 18/31 (58%) patients. Four (13%) patients experienced infusion reactions, all grade 1-2. Elotuzumab plus lenalidomide/dexamethasone is under investigation for SMM.

• Authors: Sundar Jagannath, Jacob Laubach, Ellice Wong, Keith Stockerl-Goldstein, Cara Rosenbaum, Madhav Dhodapkar, Ying-Ming Jou, Mark Lynch, Michael Robbins, Suresh Shelat, Kenneth C Anderson, Paul G Richardson
• Journal: British journal of haematology (Br J Haematol) Vol. 182 Issue 4 Pg. 495-503 (08 2018) ISSN: 1365-2141 [Electronic] England
• PMID: 29808907 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antigens, CD
• Neoplasm Proteins
• elotuzumab
• Dexamethasone
• Lenalidomide

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antibody-Dependent Cell Cytotoxicity (drug effects)
• Antigens, CD (blood, immunology)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Dexamethasone (administration & dosage, adverse effects)
• Disease-Free Survival
• Female
• Humans
• Killer Cells, Natural (immunology, metabolism)
• Lenalidomide (administration & dosage, adverse effects)
• Male
• Middle Aged
• Neoplasm Proteins (blood, immunology)
• Smoldering Multiple Myeloma (blood, drug therapy, immunology, mortality)
• Survival Rate