Evidence map›Paper›PMID 33910333›Full record

Trial reportHaematologica2021

Carfilzomib or bortezomib in combination with cyclophosphamide and dexamethasone followed by carfilzomib maintenance for patients with multiple myeloma after one prior therapy: results from a multicenter, phase II, randomized, controlled trial (MUK

Kwee L Yong, Samantha Hinsley, Holger W Auner, Ceri Bygrave, Martin F Kaiser, Karthik Ramasamy, Ruth M De Tute, Debbie Sherratt, Louise Flanagan, Mamta Garg and 9 more

Open access · goldAbstract readClinical Trial, Phase IIMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Haematologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed, 1 pooled it
1.3field-weighted citation impact, top 20% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Co-Occurrence of Cytogenetic Abnormalities and High-Risk Disease in Newly Diagnosed and Relapsed/Refractory Multiple Myeloma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025
    Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Review
  6. Article
  7. Review
  8. Article
  9. Multiple myeloma.Nature reviews. Disease primers · 2024
    Review
  10. Review
  11. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 14 institutions in 3 countries.

Kwee L YongCancer Institute, University College London, London. kwee.yong@ucl.ac.uk.
Samantha HinsleyClinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds.
Holger W AunerDepartment of Immunology and Inflammation and The Hugh and Josseline Langmuir Centre for Myeloma Research, Imperial College London, London.
Ceri BygraveCardiff and Vale University Health Board, Cardiff.
Martin F KaiserThe Institute of Cancer Research, London, UK and The Royal Marsden Hospital NHS Foundation Trust, London.
Karthik RamasamyDepartment of Clinical Haematology, Oxford University Hospitals NHS Trust, Oxford.
Ruth M De TuteDepartment of Clinical Haematology, Leeds Teaching Hospitals NHS Trust, Leeds.
Debbie SherrattClinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds.
Louise FlanaganClinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds.
Mamta GargDepartment of Haematology, University Hospitals of Leicester NHS Trust, Leicester.
Stephen HawkinsThe Clatterbridge Cancer Centre, Liverpool.
Catherine WilliamsCentre for Clinical Haematology, Nottingham University Hospitals, Nottingham.
Jamie CavenaghDepartment of Haematology, St Bartholomew's Hospital, London.
Neil K RabinDepartment of Haematology, University College Hospital, London.
James CroftThe Institute of Cancer Research, London, UK and The Royal Marsden Hospital NHS Foundation Trust, London.
Gareth MorganPerlmutter Cancer Center, NYU Langone Health, New York.
Faith DaviesPerlmutter Cancer Center, NYU Langone Health, New York.
Roger G OwenHaematological Malignancy Diagnostic Service (HMDS), St James's University Hospital, Leeds.
Sarah R BrownClinical Trials Research Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds.
University of Leeds · GBInstitute of Cancer Research · GBNYU Langone Health · USCancer Institute (WIA) · INCardiff and Vale University Health Board · GBClatterbridge Cancer Centre NHS Foundation Trust · GBImperial College London · GBLeeds Teaching Hospitals NHS Trust · GBNottingham University Hospitals NHS Trust · GBOxford University Hospitals NHS Trust · GBSt Bartholomew's Hospital · GBSt James's University Hospital · GBUniversity College London · GBUniversity Hospitals of Leicester NHS Trust · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The proteasome inhibitors, carfilzomib and bortezomib, are widely used to treat myeloma but head-to-head comparisons have produced conflicting results. We compared the activity of these proteasome inhibitors in combination with cyclophosphamide and dexamethasone (KCd vs. VCd) in second-line treatment using fixed duration therapy and evaluated the efficacy of carfilzomib maintenance. MUKfive was a phase II controlled, parallel group trial that randomized patients (2:1) to KCd (n=201) or VCd (n=99); responding patients on carfilzomib were randomized to maintenance carfilzomib (n=69) or no further treatment (n=72). Primary endpoints were: (i) very good partial response (non-inferiority, odds ratio [OR] 0.8) at 24 weeks, and (ii) progression-free survival. More participants achieved a very good partial response or better with carfilzomib than with bortezomib (40.2% vs. 31.9%, OR=1.48, 90% confidence interval [CI]: 0.95, 2.31; non-inferior), with a trend for particular benefit in patients with adverse-risk disease. KCd was associated with higher overall response (partial response or better, 84.0% vs. 68.1%, OR=2.72, 90% CI: 1.62, 4.55, P=0.001). Neuropathy (grade ≥3 or ≥2 with pain) was more common with bortezomib (19.8% vs. 1.5%, P<0.0001), while grade ≥3 cardiac events and hypertension were only reported in the KCd arm (3.6% each). The median progression-free survival in the KCd arm was 11.7 months vs. 10.2 months in the VCd arm (hazard ratio [HR]=0.95, 80% CI: 0.77, 1.18). Carfilzomib maintenance was associated with longer progression-free survival, median 11.9 months vs. 5.6 months for no maintenance (HR 0.59, 80% CI: 0.46-0.77, P=0.0086). When used as fixed duration therapy in first relapase, KCd is at least as effective as VCd, and carfilzomib is an effective maintenance agent. This trial was registered with International Standard Randomised Controlled Trial Number (ISRCTN) identifier: ISRCTN17354232.

Indexed as

Multiple MyelomaAntineoplastic Combined Chemotherapy ProtocolsBortezomibCyclophosphamideDexamethasoneHumansOligopeptidesBortezomibcarfilzomibCyclophosphamideDexamethasoneOligopeptides

Identifiers

PMID33910333
PMCPMC8485692
OpenAlexW3158532759

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.