Randomized phase 2 study

Elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM

Andrzej Jakubowiak, Massimo Offidani, Brigitte Pégourie, Javier de la Rubia, Laurent Garderet, Kamel Laribi, Alberto Bosi, Roberto Marasca, Jacob P. Laubach, Ann Mohrbacher, Angelo Michele Carella, Anil K. Singhal, L. Claire Tsao, Mark Lynch, Eric Bleickardt, Ying Ming Jou, Michael Robbins, Giuseppe Antonio Palumbo

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

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 5 .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.

Original languageEnglish
Pages (from-to)2833-2840
Number of pages8
JournalBlood
Volume127
Issue number23
DOIs
Publication statusPublished - Jun 9 2016

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Refractory materials
Dexamethasone
Disease-Free Survival
elotuzumab
Bortezomib
Hazards
Multiple Myeloma
Toxicity
Alleles
Confidence Intervals
Premedication

ASJC Scopus subject areas

  • Immunology
  • Biochemistry
  • Hematology
  • Cell Biology

Cite this

Jakubowiak, A., Offidani, M., Pégourie, B., de la Rubia, J., Garderet, L., Laribi, K., ... Palumbo, G. A. (2016). Randomized phase 2 study: Elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood, 127(23), 2833-2840. https://doi.org/10.1182/blood-2016-01-694604

Randomized phase 2 study : Elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. / Jakubowiak, Andrzej; Offidani, Massimo; Pégourie, Brigitte; de la Rubia, Javier; Garderet, Laurent; Laribi, Kamel; Bosi, Alberto; Marasca, Roberto; Laubach, Jacob P.; Mohrbacher, Ann; Carella, Angelo Michele; Singhal, Anil K.; Tsao, L. Claire; Lynch, Mark; Bleickardt, Eric; Jou, Ying Ming; Robbins, Michael; Palumbo, Giuseppe Antonio.

In: Blood, Vol. 127, No. 23, 09.06.2016, p. 2833-2840.

Research output: Contribution to journalArticle

Jakubowiak, A, Offidani, M, Pégourie, B, de la Rubia, J, Garderet, L, Laribi, K, Bosi, A, Marasca, R, Laubach, JP, Mohrbacher, A, Carella, AM, Singhal, AK, Tsao, LC, Lynch, M, Bleickardt, E, Jou, YM, Robbins, M & Palumbo, GA 2016, 'Randomized phase 2 study: Elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM', Blood, vol. 127, no. 23, pp. 2833-2840. https://doi.org/10.1182/blood-2016-01-694604
Jakubowiak A, Offidani M, Pégourie B, de la Rubia J, Garderet L, Laribi K et al. Randomized phase 2 study: Elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood. 2016 Jun 9;127(23):2833-2840. https://doi.org/10.1182/blood-2016-01-694604
Jakubowiak, Andrzej ; Offidani, Massimo ; Pégourie, Brigitte ; de la Rubia, Javier ; Garderet, Laurent ; Laribi, Kamel ; Bosi, Alberto ; Marasca, Roberto ; Laubach, Jacob P. ; Mohrbacher, Ann ; Carella, Angelo Michele ; Singhal, Anil K. ; Tsao, L. Claire ; Lynch, Mark ; Bleickardt, Eric ; Jou, Ying Ming ; Robbins, Michael ; Palumbo, Giuseppe Antonio. / Randomized phase 2 study : Elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. In: Blood. 2016 ; Vol. 127, No. 23. pp. 2833-2840.
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abstract = "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 5 .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.",
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AU - de la Rubia, Javier

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