title: Elotuzumab in combination with thalidomide and low-dose dexamethasone: a phase 2 single-arm safety study in patients with relapsed/refractory multiple myeloma.
abstract: Elotuzumab is an immunostimulatory, humanized immunoglobulin G1 monoclonal antibody that selectively targets and kills signalling lymphocytic activation molecule family member 7-expressing myeloma cells. We evaluated the safety and tolerability of elotuzumab 10 mg/kg combined with thalidomide 50-200 mg and dexamethasone 40 mg (with/without cyclophosphamide 50 mg) in patients with relapsed/refractory multiple myeloma (RRMM). The primary endpoint was the proportion of grade ≥3 non-haematological adverse events (AEs); other endpoints included the number of dose reductions/discontinuations and efficacy. Forty patients were treated, who had a median of three previous therapies, including bortezomib (98%) and lenalidomide (73%). Grade ≥3 non-haematological AEs were reported in 63% of patients, most commonly asthenia (35%) and peripheral oedema (25%). Six (15%) patients had an infusion reaction. Twenty-six (65%) patients had ≥1 dose reduction/discontinuation due to an AE, none related to elotuzumab. Overall response rate was 38%; median progression-free survival was 3·9 months. Median overall survival was 16·3 months and the 1-year survival rate was 63%. Minimal incremental toxicity was observed with addition of elotuzumab to thalidomide/dexamethasone with or without cyclophosphamide, and efficacy data suggest clinical benefit in a highly pre-treated population. Elotuzumab combined with thalidomide may provide an additional treatment option for patients with RRMM.
authors.affiliation: Haematology Department, Complejo Asistencial Universitario de Salamanca/Instituto Biosanitario de Salamanca (IBSAL), Salamanca, Spain. mvmateos@usal.es.
authors.forename: María-Victoria
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Haematology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Granell
authors.affiliation: Institut Català d'Oncologia, Institut Josep Carreras, Hospital Germans Trias, Pujol, Badalona, Spain.
authors.forename: Albert
authors.initials: A
authors.lastname: Oriol
authors.affiliation: Haematology Department, Hospital Universitario 12 de Octubre, Medicine School Complutense University, CNIO, Madrid, Spain.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Martinez-Lopez
authors.affiliation: Haematology Department, Hospital Clinica, IDIBAPS, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Blade
authors.affiliation: Complejo Hospitalario Universitario de Canarias, Santa Cruz de Tenerife, Spain.
authors.forename: Miguel T
authors.initials: MT
authors.lastname: Hernandez
authors.affiliation: Haematology Department, Hospital Universitario Virgen del Rocío, Sevilla, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: Martín
authors.affiliation: Haematology Department, Hospital Universitario Vall d'Hebron, Barcelona, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Gironella
authors.affiliation: Oncology Clinical Development, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Lynch
authors.affiliation: Oncology Clinical Development, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Bleickardt
authors.affiliation: Global Regulatory Safety and Biometrics, Bristol-Myers Squibb, Princeton, NJ, USA.
authors.forename: Prashni
authors.initials: P
authors.lastname: Paliwal
authors.affiliation: AbbVie Biotherapeutics Inc. (ABR), Redwood City, CA, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Singhal
authors.affiliation: Clinical and Translational Medicine, Clínica Universidad de Navarra - CIMA (Centro de Investigación Médica Aplicada) - IdiSNA (Instituto de Investigación Sanitaria de Navarra), Pamplona, Spain.
authors.forename: Jesus
authors.initials: J
authors.lastname: San-Miguel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D009367:Neoplasm Staging; D012008:Recurrence; D019233:Retreatment; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C546027:elotuzumab; D013792:Thalidomide; D003907:Dexamethasone
keywords: elotuzumab; multiple myeloma; relapsed/refractory; signalling lymphocytic activation molecule family member 7; thalidomide