Randomized phase 2 study of elotuzumab plus bortezomib/dexamethasone (Bd) versus Bd for relapsed/refractory multiple myeloma
Mené sur 152 patients atteints d'un myélome multiple récidivant/réfractaire, cet essai randomisé international de phase II évalue l'efficacité, du point de vue de la survie sans progression, et la toxicité de l'ajout d'élotuzumab à un traitement combinant bortézomib et dexaméthasone
Elotuzumab, an immunostimulatory antibody, prolongs PFS with no added clinical toxicity when combined with Bd versus Bd alone in RRMM.Based on results from this phase 2 study, further investigation of elotuzumab with a proteasome inhibitor in RRMM is warranted. 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 versus 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) versus 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 versus 9.8 in EBd-treated patients homozygous for the low-affinity allele. ORR was 66% (EBd) versus 63% (Bd). Very good partial response or better occurred in 36% of patients (EBd) versus 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 versus 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 versus Bd alone. ClinicalTrials.gov NCT01478048.