Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM.
In this proof-of-concept, open-label, phase 2 study, patients with relapsed/refractory multiple myeloma (RRMM) received elotuzumab with bortezomib and dexamethasone (EBd) or bortezomib and dexamethasone (Bd) until disease progression/unacceptable toxicity. Primary endpoint was progression-free survival (PFS); secondary/exploratory endpoints included overall response rate (ORR) and overall survival (OS). Two-sided 0.30 significance level was specified (80% power, 103 events) to detect hazard ratio (HR) of 0.69. Efficacy and safety analyses were performed on all randomized patients and all treated patients, respectively. Of 152 randomized patients (77 EBd, 75 Bd), 150 were treated (75 EBd, 75 Bd). PFS was greater with EBd vs Bd (HR, 0.72; 70% confidence interval [CI], 0.59-0.88; stratified log-rank P = .09); median PFS was longer with EBd (9.7 months) vs Bd (6.9 months). In an updated analysis, EBd-treated patients homozygous for the high-affinity FcγRIIIa allele had median PFS of 22.3 months vs 9.8 months in EBd-treated patients homozygous for the low-affinity allele. ORR was 66% (EBd) vs 63% (Bd). Very good partial response or better occurred in 36% of patients (EBd) vs 27% (Bd). Early OS results, based on 40 deaths, revealed an HR of 0.61 (70% CI, 0.43-0.85). To date, 60 deaths have occurred (28 EBd, 32 Bd). No additional clinically significant adverse events occurred with EBd vs Bd. Grade 1/2 infusion reaction rate was low (5% EBd) and mitigated with premedication. In patients with RRMM, elotuzumab, an immunostimulatory antibody, appears to provide clinical benefit without added clinically significant toxicity when combined with Bd vs Bd alone. Registered to ClinicalTrials.gov as NCT01478048.
Myeloma Program, Section of Hematology/Oncology, University of Chicago Medical Center, Chicago, IL;
Andrzej
0000-0002-2597-6822
A
Jakubowiak
Clinica di Ematologia, Azienda Ospedaliero Universitaria Ospedali Riuniti di Ancona, Ancona, Italy;
Massimo
M
Offidani
Centre Hospitalier Universitaire de Grenoble-Hôpital Albert Michallon, Grenoble, France;
Brigitte
B
Pégourie
Hospital Universitario Doctor Peset and Universidad Católica "San Vicente Mártir," Valencia, Spain;
Javier
J
De La Rubia
Service d'hématologie, Hôpital Saint Antoine, Paris, France;
Laurent
L
Garderet
Department of Hematology, Centre Hospitalier, Le Mans, France;
Kamel
K
Laribi
Department of Hematology, Azienda Ospedaliero Universitaria Careggi, Florence, Italy;
Alberto
A
Bosi
Department of Hematology, Azienda Ospedaliera Universitaria-Policlinico di Modena, Modena, Italy;
Roberto
R
Marasca
Department of Hematology/Oncology, Dana-Farber Cancer Institute, Boston, MA;
Jacob
J
Laubach
Division of Hematology, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA;
Ann
A
Mohrbacher
Hematology Unit, Istituto di Ricovero e Cura a Carattere Scientifico San Martino-Istituto Scientifico Tumori, Genoa, Italy;
Angelo Michele
AM
Carella
Statistics, AbbVie Biotherapeutics Inc, Redwood City, CA;
Anil K
AK
Singhal
Statistics, AbbVie Biotherapeutics Inc, Redwood City, CA;
L Claire
LC
Tsao
Oncology Clinical Development, Bristol-Myers Squibb, Wallingford, CT;
Mark
M
Lynch
Oncology Clinical Development, Bristol-Myers Squibb, Wallingford, CT;
Eric
E
Bleickardt
Global Biometric Sciences, Bristol-Myers Squibb, Hopewell, NJ;
Ying-Ming
YM
Jou
Exploratory Clinical and Translational Research-Oncology, Bristol-Myers Squibb, Princeton, NJ; and.
Michael
M
Robbins
Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
Antonio
A
Palumbo
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage* / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; C546027:elotuzumab; D000069286:Bortezomib; D003907:Dexamethasone