TY - JOUR
T1 - Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003)
T2 - A randomised, open-label, phase 3 trial
AU - Miguel, Jesus San
AU - Weisel, Katja
AU - Moreau, Philippe
AU - Lacy, Martha
AU - Song, Kevin
AU - Delforge, Michel
AU - Karlin, Lionel
AU - Goldschmidt, Hartmut
AU - Banos, Anne
AU - Oriol, Albert
AU - Alegre, Adrian
AU - Chen, Christine
AU - Cavo, Michele
AU - Garderet, Laurent
AU - Ivanova, Valentina
AU - Martinez-Lopez, Joaquin
AU - Belch, Andrew
AU - Palumbo, Antonio
AU - Schey, Stephen
AU - Sonneveld, Pieter
AU - Yu, Xin
AU - Sternas, Lars
AU - Jacques, Christian
AU - Zaki, Mohamed
AU - Dimopoulos, Meletios
N1 - Funding Information:
This research was funded by Celgene Corporation. We thank the patients who volunteered to participate in this study and staff members at the study sites who cared for them, and the representatives of the sponsors who were involved in data gathering and analyses. We thank Eva Polk and Anna Georgieva from Excerpta Medica, for their writing assistance, which was funded by Celgene Corporation.
Funding Information:
JSM has had a consultancy or advisory role, and has received honoraria from Celgene Corporation, Jansen, Millennium, Novartis, and Onyx. KW has had a consultancy or advisory role and has received honoraria from Celgene Corporation. PM has had a consultancy or advisory role and has received honoraria from Celgene Corporation, Millennium, and Janssen. ML has received research funding from Celgene Corporation. KS has had a consultancy or advisory role, received honoraria, and has received research funding from Celgene Corporation and Janssen. MD and AA have had a consultancy or advisory role and received research funding from Celgene Corporation and Janssen. LK has had a consultancy or advisory role and provided export testimony for Celgene Corporation, and received honoraria and other remuneration from Celgene Corporation and Janssen. HG has had a consultancy or advisory role, received honoraria and received research funding from Celgene Corporation and Janssen. AO has had a consultancy and advisory role for Celgene Corporation and Janssen. CC has had a consultancy or advisory role, received honoraria, and received research funding from Celgene Corporation. MC has had a consultancy or advisory role and has received honoraria from Celgene Corporation, Janssen, and Millennium. JM-L has received honoraria and research funding from Celgene Corporation. AB has received research funding from Celgene Corporation. AP has received honoraria and was a member of the board of an advisory committee for Celgene Corporation and Janssen-Cilag, and received honoraria from OrthoBiotech. SS has had a consultancy role and received honoraria from Celgene Corporation. PS has received honoraria and funding from Celgene Corporation, Janssen, and Onyx. XY, LS, CJ, and MZ are employed and have equity ownership with Celgene Corporation. MD has had a consultancy or advisory role for Celgene Corporation and Ortho Biotech, and has received research funding from Genesis Pharma. The other authors declare that they have no conflicts of interest.
PY - 2013/10
Y1 - 2013/10
N2 - Background: Few effective treatments exist for patients with refractory or relapsed and refractory multiple myeloma not responding to treatment with bortezomib and lenalidomide. Pomalidomide alone has shown limited efficacy in patients with relapsed multiple myeloma, but synergistic effects have been noted when combined with dexamethasone. We compared the efficacy and safety of pomalidomide plus low-dose dexamethasone with high-dose dexamethasone alone in these patients. Methods: This multicentre, open-label, randomised phase 3 trial was undertaken in Australia, Canada, Europe, Russia, and the USA. Patients were eligible if they had been diagnosed with refractory or relapsed and refractory multiple myeloma, and had failed at least two previous treatments of bortezomib and lenalidomide. They were assigned in a 2:1 ratio with a validated interactive voice and internet response system to either 28 day cycles of pomalidomide (4 mg/day on days 1-21, orally) plus low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally) or high-dose dexamethasone (40 mg/day on days 1-4, 9-12, and 17-20, orally) until disease progression or unacceptable toxicity. Stratification factors were age (≤75 years vs >75 years), disease population (refractory vs relapsed and refractory vs bortezomib intolerant), and number of previous treatments (two vs more than two). The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01311687, and with EudraCT, number 2010-019820-30. Findings: The accrual for the study has been completed and the analyses are presented. 302 patients were randomly assigned to receive pomalidomide plus low-dose dexamethasone and 153 high-dose dexamethasone. After a median follow-up of 10·0 months (IQR 7·2-13·2), median PFS with pomalidomide plus low-dose dexamethasone was 4·0 months (95% CI 3·6-4·7) versus 1·9 months (1·9-2·2) with high-dose dexamethasone (hazard ratio 0·48 [95% CI 0·39-0·60]; p<0·0001). The most common grade 3-4 haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups were neutropenia (143 [48%] of 300 vs 24 [16%] of 150, respectively), anaemia (99 [33%] vs 55 [37%], respectively), and thrombocytopenia (67 [22%] vs 39 [26%], respectively). Grade 3-4 non-haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups included pneumonia (38 [13%] vs 12 [8%], respectively), bone pain (21 [7%] vs seven [5%], respectively), and fatigue (16 [5%] vs nine [6%], respectively). There were 11 (4%) treatment-related adverse events leading to death in the pomalidomide plus low-dose dexamethasone group and seven (5%) in the high-dose dexamethasone group. Interpretation: Pomalidomide plus low-dose dexamethasone, an oral regimen, could be considered a new treatment option in patients with refractory or relapsed and refractory multiple myeloma. Funding: Celgene Corporation.
AB - Background: Few effective treatments exist for patients with refractory or relapsed and refractory multiple myeloma not responding to treatment with bortezomib and lenalidomide. Pomalidomide alone has shown limited efficacy in patients with relapsed multiple myeloma, but synergistic effects have been noted when combined with dexamethasone. We compared the efficacy and safety of pomalidomide plus low-dose dexamethasone with high-dose dexamethasone alone in these patients. Methods: This multicentre, open-label, randomised phase 3 trial was undertaken in Australia, Canada, Europe, Russia, and the USA. Patients were eligible if they had been diagnosed with refractory or relapsed and refractory multiple myeloma, and had failed at least two previous treatments of bortezomib and lenalidomide. They were assigned in a 2:1 ratio with a validated interactive voice and internet response system to either 28 day cycles of pomalidomide (4 mg/day on days 1-21, orally) plus low-dose dexamethasone (40 mg/day on days 1, 8, 15, and 22, orally) or high-dose dexamethasone (40 mg/day on days 1-4, 9-12, and 17-20, orally) until disease progression or unacceptable toxicity. Stratification factors were age (≤75 years vs >75 years), disease population (refractory vs relapsed and refractory vs bortezomib intolerant), and number of previous treatments (two vs more than two). The primary endpoint was progression-free survival (PFS). Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01311687, and with EudraCT, number 2010-019820-30. Findings: The accrual for the study has been completed and the analyses are presented. 302 patients were randomly assigned to receive pomalidomide plus low-dose dexamethasone and 153 high-dose dexamethasone. After a median follow-up of 10·0 months (IQR 7·2-13·2), median PFS with pomalidomide plus low-dose dexamethasone was 4·0 months (95% CI 3·6-4·7) versus 1·9 months (1·9-2·2) with high-dose dexamethasone (hazard ratio 0·48 [95% CI 0·39-0·60]; p<0·0001). The most common grade 3-4 haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups were neutropenia (143 [48%] of 300 vs 24 [16%] of 150, respectively), anaemia (99 [33%] vs 55 [37%], respectively), and thrombocytopenia (67 [22%] vs 39 [26%], respectively). Grade 3-4 non-haematological adverse events in the pomalidomide plus low-dose dexamethasone and high-dose dexamethasone groups included pneumonia (38 [13%] vs 12 [8%], respectively), bone pain (21 [7%] vs seven [5%], respectively), and fatigue (16 [5%] vs nine [6%], respectively). There were 11 (4%) treatment-related adverse events leading to death in the pomalidomide plus low-dose dexamethasone group and seven (5%) in the high-dose dexamethasone group. Interpretation: Pomalidomide plus low-dose dexamethasone, an oral regimen, could be considered a new treatment option in patients with refractory or relapsed and refractory multiple myeloma. Funding: Celgene Corporation.
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U2 - 10.1016/S1470-2045(13)70380-2
DO - 10.1016/S1470-2045(13)70380-2
M3 - Article
C2 - 24007748
AN - SCOPUS:84884702483
VL - 14
SP - 1055
EP - 1066
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 11
ER -