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R. Mina et al.
genetic features, such as bi-allelic inactivation, was still unknown, and therefore it could not be addressed in our work.
The prolonged use of carfilzomib in our study may have had a beneficial role in HiR patients. The available evi- dence suggests that continuous therapy could be superior to fixed duration therapy and could be of particular bene- fit to HiR patients. However, continuous therapy is not sufficient to overcome the poor prognosis of adverse CA. For example, in the FIRST study, the median PFS of HiR patients treated with continuous Rd was only 9 months.14,15 In our analysis, the median duration of thera- py was similar between SR and HiR patients (16.9 vs. 14.6 months), meaning that both groups of patients benefited from prolonged treatment. In conclusion, the results of our pooled analysis suggest that a carfilzomib-based treat- ment is effective as upfront treatment for HiR, transplant- ineligible MM patients. Carfilzomib may contribute to fill the gap between SR and HiR patients, thus improving the poor prognosis of the latter. Our results provide the basis for a further investigation of carfilzomib as upfront thera- py for the treatment of HiR MM patients.
Disclosures
RM has received honoraria from Sanofi, Celgene, Takeda and Janssen; has served on the advisory boards for Sanofi, Takeda, and Janssen; has received consultancy fees from Janssen; MTP has received honoraria from Celgene, Janssen- Cilag, BMS, Takeda, and Amgen, has served on the advisory boards for Celgene, Janssen-Cilag, BMS, Takeda, and Amgen; AML has received honoraria from Janssen, Celgene, Bristol- Myers Squibb, and Servier, has received clinical trial support from Novartis, AbbVie, Roche, Amgen, and Celgene, has served on the advisory boards for AbbVie, Amgen, Takeda, and Servier, and has undertaken consultancy for Incyte; StB has received honoraria for attending meetings from Janssen and Celgene; PM has received personal fees from Amgen, Novartis, BMS, Celgene, Janssen, and Takeda; GB has served on the advisory boards for Novartis, Celgene, and Amgen; MC has received grants from Janssen and Celgene; has received personal fees from Janssen, Celgene, Amgen, BMS, and Takeda; AP is currently a GlaxoSmithKline AG employee; VM has received speaking fees from and served on the advisory boards for Amgen, Celgene, Janssen, and Takeda; GG has served on the advisory boards for Janssen, AbbVie, Astra-Zeneca, and Sunesys, has served on the speakers’ bureaus for Janssen,
Gilead, and AbbVie; PO has served on the advisory boards for Janssen; MB has received honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers Squibb, and AbbVie; has served on the advisory boards for Janssen and GSK; has received research funding from Sanofi, Celgene, Amgen, Janssen, Novartis, Bristol-Myers Squibb, and Mundipharma; SB has received honoraria from Bristol-Myers Squibb, Celgene, Amgen and Janssen, has served on the advisory boards for Amgen, Karyopharm, Janssen and Celgene, and has received consultancy fees from Takeda and Janssen. The remaining authors have no conflicts of interest to disclose.
Contributions
RM, FB, PO, MB and SB made substantial contributions to the conception or design of the analysis; all authors are responsi- ble for the acquisition, analysis or interpretation of data; RM, FB, AC, MG, PO and SB made the first draft of the manuscript; AC carried out the statistical analysis; MB and SB supervised the analysis; all authors critically revised the manuscript for impor- tant intellectual content; all authors gave their final approval of the version to be published; all authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Acknowledgments
We thank the patients who took part in these studies and their families, the study co-investigators, nurses and co-ordinators at each of the clinical sites. We would also like to thank the nurses Rosalia Capobianco and Giacomo Castorina, and the data man- agers Debora Caldarazzo and Federica Leotta.
Funding
The IST-CAR-561 (NCT01857115) study was sponsored by Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON, the Netherlands), in collaboration with Fondazione Neoplasie Sangue ONLUS (Italy). The IST-CAR-506 (NCT01346787) study was sponsored by the HOVON Foundation and co-sponsored by Fondazione Neoplasie Sangue ONLUS. Both trials were supported by funding from AMGEN (Onyx Pharmaceuticals), which had no role in study design, data collection, data analysis, data interpretation, writing of the report or publication of this article. The corresponding author had full access to all the data in the two studies, and had final responsi- bility for the decision to prepare and submit this manuscript for publication, together with the other authors.
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