Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM

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 survi...

Full description

Saved in:
Bibliographic Details
Published in:Blood Vol. 127; no. 23; pp. 2833 - 2840
Main Authors: Jakubowiak, Andrzej, Offidani, Massimo, Pégourie, Brigitte, De La Rubia, Javier, Garderet, Laurent, Laribi, Kamel, Bosi, Alberto, Marasca, Roberto, Laubach, Jacob, Mohrbacher, Ann, Carella, Angelo Michele, Singhal, Anil K., Tsao, L.Claire, Lynch, Mark, Bleickardt, Eric, Jou, Ying-Ming, Robbins, Michael, Palumbo, Antonio
Format: Journal Article
Language:English
Published: United States Elsevier Inc 09-06-2016
American Society of Hematology
Subjects:
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal, Humanized - administration & dosage
Antibodies, Monoclonal, Humanized - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Bortezomib - administration & dosage
Bortezomib - adverse effects
Clinical Trials and Observations
Dexamethasone - administration & dosage
Dexamethasone - adverse effects
Drug Resistance, Neoplasm - drug effects
Female
Humans
Male
Middle Aged
Multiple Myeloma - drug therapy
Neoplasm Recurrence, Local - drug therapy
Treatment Outcome
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. •Elotuzumab, an immunostimulatory antibody, prolongs PFS with no added clinical toxicity when combined with Bd vs Bd alone in RRMM.•Based on results from this phase 2 study, further investigation of elotuzumab with a proteasome inhibitor in RRMM is warranted.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2016-01-694604