TY - JOUR
T1 - Elotuzumab monotherapy in patients with smouldering multiple myeloma
T2 - a phase 2 study
AU - Jagannath, Sundar
AU - Laubach, Jacob
AU - Wong, Ellice
AU - Stockerl-Goldstein, Keith
AU - Rosenbaum, Cara
AU - Dhodapkar, Madhav
AU - Jou, Ying Ming
AU - Lynch, Mark
AU - Robbins, Michael
AU - Shelat, Suresh
AU - Anderson, Kenneth C.
AU - Richardson, Paul G.
N1 - Publisher Copyright:
© 2018 The Authors. British Journal of Haematology published by John Wiley & Sons Ltd
PY - 2018/8
Y1 - 2018/8
N2 - 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.
AB - 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.
KW - elotuzumab
KW - monoclonal antibody
KW - multiple myeloma
KW - natural killer cells
KW - smouldering multiple myeloma
UR - http://www.scopus.com/inward/record.url?scp=85047730624&partnerID=8YFLogxK
U2 - 10.1111/bjh.15384
DO - 10.1111/bjh.15384
M3 - Article
C2 - 29808907
AN - SCOPUS:85047730624
SN - 0007-1048
VL - 182
SP - 495
EP - 503
JO - British Journal of Haematology
JF - British Journal of Haematology
IS - 4
ER -