Page 177 - 2021_10-Haematologica-web

Carfilzomib or bortezomib in first relapse MM
that achieved in response to bortezomib, and in the effica- cy of maintenance therapy. With an increasing number of patients who, at first relapse, are exposed or refractory to bortezomib and lenalidomide, KCd followed by carfil- zomib maintenance represents an economically competi- tive and clinically feasible regimen, reserving other novel agent combinations such as those with CD38 and poma- lidomide, or the new agents targeting B-cell maturation antigen and T-cell redirecting therapies, for a subsequent relapse or progression. Further studies are needed to explore the potential greater activity of carfilzomib in patients with adverse-risk disease, in whom the tolerabil- ity during prolonged use may make this the proteasome inhibitor of choice.
Disclosures
KLY reports grants and personal fees from Amgen, Celgene, Novartis, Janssen, and Takeda. HWA reports grants from Myeloma UK, during the conduct of the study; grants from Amgen and personal fees from Amgen, Karyopharm, Takeda, Novartis, Janssen, outside the submitted work. MFK reports per- sonal fees from Abbvie and Amgen; grants and personal fees from Celgene; grants, personal fees and other from Janssen; and per- sonal fees and other from Takeda, outside the submitted work. KR reports grants and personal fees from Celgene, Janssen, Takeda, and Amgen; and personal fees from Abbvie, Sanofi, Oncopeptides, outside the submitted work. LF reports grants and non-financial support from Amgen, during the conduct of the study. SHa reports personal fees from Amgen, outside the submit- ted work. CW reports personal fees from Amgen, outside the sub- mitted work. NKR reports personal fees from Amgen, during the conduct of the study. JCr reports personal fees from Celgene, out- side the submitted work. GM reports other from AbbVie, Amgen, Celgene, Janssen, Oncopeptide, Roche, and Takeda, outside the submitted work. FD reports grants and other from Celgene and Janssen; and other from AbbVie, Adaptive Biotech, Amgen, Oncopeptide, Roche, Sanofi, and Takeda, outside the submitted work. RGO reports personal fees from Amgen, Janssen, Takeda, and Adaptive Biotech. RD (RMdT), SHi, DS, MG, JCa, CB, and SRB have nothing to disclose.
Contributions
KLY, DS, LF, CW, JCa, RGO, GM, FD and SRB designed the study. KLY, KR, MG, NR, CW, JCa, NKR, RGO and MFK performed the research and collected data. DS and LF performed trial and data management. HWA, SHa and CB performed independent clinical review of endpoint data. SHi and SRB per- formed statistical analyses. RMdT and RGO performed analysis of minimal residual disease. MFK and JCr performed central assessment of genetic risk. KLY, HWA, CB, SHi and SRB wrote the manuscript. All authors provided input into, and had control over, the final version of the manuscript.
Acknowledgments
The authors are deeply indebted to all the participants in this study and to their families and carers. We would like to thank all staff, past and present, at the participating hospitals: University College London Hospital, Leicester Royal Infirmary, Churchill Hospital Oxford, Nottingham University Hospitals, King’s College Hospital, Imperial College London Healthcare NHS Trust, Royal Hallamshire Hospital, St James University Hospital, University Hospital of Wales, University Hospital Southampton NHS Foundation Trust, Birmingham Heartlands Hospital, Bristol Haematology and Oncology Centre, Manchester Royal Infirmary, Royal Bournemouth General Hospital, The Christie Hospital, Royal Devon & Exeter Hospital, Princess Royal University Hospital, Royal Marsden Hospital, Lincoln County Hospital, New Cross Hospital, Ninewells Hospital, Pilgrim Hospital Boston, St Bartholomew's Hospital, Beatson West of Scotland Cancer Centre, University Hospital of North Tees, Queens Hospital Burton, Royal Cornwall Hospital, Royal Sussex County Hospital, Torbay District General Hospital, University Hospital Coventry, Addenbrooke’s Hospital, Ayr Hospital, Countess of Chester Hospital, George Eliot Hospital, Grantham and District Hospital, Crosshouse Hospital, and Northwick Park Hospital. The authors would like to thank the Myeloma UK Clinical Trials Coordinating Office Trial Steering Committee and Data Monitoring and Ethics Committee members, without whom the trial would not have been possible: Chris Twelves, Kevin Boyd, Michael Brown, Philippe Moreau, Simon Rule, Tomasz Burzykowski, Curly Morris, Alan Anthoney, Graham Jackson, James Wason, Malcolm Ranson, Richard Soutar, and Roger Ahern. The authors are also grateful to the staff at Leeds Institute of Clinical Trials Research, who made this study pos- sible: Lucy Bailey, Sue Bourne, Wendy Burton, Jenny Fell, Suja George, Walter Gregory, Diane Hartley, Emma Ingleson, Jessica Kendall, Paul McGarry, Rachel Naylor, Matthew Newby, Katie Robinson, Saqib Saghir, Alex Szubert, and Alan Wan.
Funding
KLY receives funding from the UCL/UCLH Biomedical Research Centre.
Data-sharing statement
Any requests for trial data will be reviewed by the trial man- agement group in the first instance. Only requests that have a methodologically sound proposal and whose proposed use of the data has been approved by the independent trial steering commit- tee will be considered. Proposals should be directed to the corre- sponding author in the first instance; to gain access; data requestors will need to sign a data access agreement. The study protocol is publicly available.15
References
1. Moreau P, San Miguel J, Sonneveld P, et al. Multiple myeloma: ESMO clinical practice guidelines for diagnosis, treatment and fol- low-up. Ann Oncol. 2017;28(suppl_4):iv52- iv61.
2. Yong K, Gonzalez-McQuire S, Szabo Z, Schoen P, Hajek R. The start of a new wave: developments in proteasome inhibition in multiple myeloma. Eur J Haematol. 2018 Mar 30. [Epub ahead of print]
3. Bringhen S, Larocca A, Rossid D, et al. Efficacy and safety of once-weekly borte- zomib in multiple myeloma patients. Blood. 2010;116(23):4745-4753.
4. Dimopoulos MA, Moreau P, Palumbo A, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myelo- ma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17(1):27-38.
5. Stewart AK, Rajkumar SV, Dimopoulos MA, et al. Carfilzomib, lenalidomide, and dexam-
ethasone for relapsed multiple myeloma. N
Engl J Med. 2015;372(2):142-152.
6. Dimopoulos M, Quach H, Mateos MV, et al. Carfilzomib, dexamethasone, and daratu- mumab versus carfilzomib and dexametha- sone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet. 2020;396(10245):186-
197.
7.Bringhen S, Milan A, Ferri C, et al.
Cardiovascular adverse events in modern myeloma therapy - incidence and risks. A
haematologica | 2021; 106(10)
2705