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

• Type of Material: Article
• Authors: Sundar Jagannath, Mt. Sinai Medical Center; Jacob Laubach, Harvard Medical School; Ellice Wong, Yale University; Keith Stockerl-Goldstein, Washington University; Cara Rosenbaum, Cornell University; Madhav Dhodapkar, Emory University; Ying-Ming Jou, Bristol Myers Squibb; Mark Lynch, Bristol Myers Squibb; Michael Robbins, Bristol Myers Squibb; Suresh Shelat, Bristol Myers Squibb; Kenneth C. Anderson, Harvard Medical School; Paul G. Richardson, Harvard Medical School
• Language: English
• Date: 2018-08-01
• Publisher: Wiley: 12 months
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1111/bjh.15384
• Title of Journal or Parent Work: British Journal of Haematology
• ISSN: 0007-1048
• Volume: 182
• Issue: 4
• Start Page: 495
• End Page: 503
• Grant/Funding Information: Editorial assistance was provided by Stephanie Wolfe at Caudex, funded by Bristol‐Myers Squibb.; Professional medical writing assistance was provided by Adam Gill at Caudex, funded by Bristol‐Myers Squibb.; This study was funded by Bristol‐Myers Squibb. Elotuzumab was developed in partnership between AbbVie Biotherapeutics and Bristol‐Myers Squibb.; This work was supported by a grant from the National Cancer Institute of the National Institutes of Health, USA (P30CA016359 to Yale Cancer Center).
• Keywords: LENALIDOMIDE PLUS DEXAMETHASONE; THALIDOMIDE; CS1; PROGRESSION; OPEN-LABEL; Science & Technology; elotuzumab; CLINICAL-COURSE; THERAPY; Hematology; monoclonal antibody; multiple myeloma; COMBINATION; natural killer cells; Life Sciences & Biomedicine; smouldering multiple myeloma
• Research Categories: Health Sciences, Oncology

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. CD56 dim (CD56 dim /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 CD56 dim 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 CD56 dim 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.