Evidence map›Paper›PMID 32145111›Full record

ArticleEuropean journal of haematology2020

c-MYC expression and maturity phenotypes are associated with outcome benefit from addition of ixazomib to lenalidomide-dexamethasone in myeloma.

Alessandra Di Bacco, Nizar J Bahlis, Nikhil C Munshi, Hervé Avet-Loiseau, Tamás Masszi, Luísa Viterbo, Ludek Pour, Peter Ganly, Michele Cavo, Christian Langer and 14 more

Registry-linked trialOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of haematology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01564537 (A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral Ixazomib), which is not on this map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.0field-weighted citation impact, top 22% 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.

NCT01564537 phase3completednot on this map

A Phase 3, Randomized, Double-Blind, Multicenter Study Comparing Oral Ixazomib (MLN9708) Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

TypeinterventionalSponsorTakedaRan2012 to 2022Enrolled722ConditionsRelapsed Multiple Myeloma, Refractory Multiple MyelomaArmsIxazomib, Lenalidomide, Dexamethasone, Placebo
3 · Its place in the literature

Who cites it

7 citing papers in PubMed, 9 citations in OpenAlex.

  1. Trial
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 13 institutions in 10 countries.

Alessandra Di BaccoMillennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), Cambridge, MA, USA.ORCID https://orcid.org/0000-0003-2072-8712
Nizar J BahlisSouthern Alberta Cancer Research Institute, University of Calgary, Calgary, AB, Canada.
Nikhil C MunshiHematologic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Hervé Avet-LoiseauHematology, IUC-Oncopole, Toulouse, France.
Tamás MassziDepartment of Haematology and Stem Cell Transplantation, St. István and St. László Hospital of Budapest, Budapest, Hungary.
Luísa ViterboInstituto Português de Oncologia do Porto Francisco Gentil, Entidade Pública Empresarial (IPOPFG, EPE), Porto, Portugal.
Ludek PourHematology and Oncology, University Hospital Brno, Brno, Czech Republic.
Peter GanlyDepartment of Haematology, Christchurch Hospital, Christchurch, New Zealand.
Michele CavoInstitute of Hematology and Medical Oncology "Seràgnoli", Bologna University School of Medicine, S.Orsola's University Hospital, Bologna, Italy.
Christian LangerUniversity Hospital of Ulm, Ulm, Germany.
Shaji K KumarDivision of Hematology, Mayo Clinic, Rochester, MN, USA.
S Vincent RajkumarDivision of Hematology, Mayo Clinic, Rochester, MN, USA.
Jonathan J KeatsTranslational Genomics Research Institute (TGEN), Phoenix, AZ, USA.
Deborah BergMillennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), Cambridge, MA, USA.
Jianchang LinMillennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), Cambridge, MA, USA.
Bin LiMillennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), Cambridge, MA, USA.
Sunita BadolaMillennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), Cambridge, MA, USA.
Lei ShenMillennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), Cambridge, MA, USA.
Jacob ZhangMillennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), Cambridge, MA, USA.
Dixie-Lee EsseltineMillennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), Cambridge, MA, USA.
Katarina LuptakovaMillennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), Cambridge, MA, USA.
Helgi van de VeldeMillennium Pharmaceuticals, Inc. (a wholly owned subsidiary of Takeda Pharmaceutical Company Limited), Cambridge, MA, USA.
Paul G RichardsonHematologic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Philippe MoreauDepartment of Hematology, University Hospital Hôtel Dieu, University of Nantes, Nantes, France.ORCID https://orcid.org/0000-0003-1780-8746
Takeda (United States) · USDana-Farber Cancer Institute · USMayo Clinic in Arizona · USChristchurch Hospital · NZInstitut universitaire du cancer de Toulouse Oncopole · FRIPO Porto · PTNantes Université · FRSAIT Polytechnic · CASemmelweis University · HUTranslational Genomics Research Institute · USUniversity Hospital Brno · CZUniversity Hospital Ulm · DEUniversity of Bologna · IT

Funding

Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
6 · The paper itself

Abstract

objectivesIn the TOURMALINE-MM1 phase 3 trial in relapsed/refractory multiple myeloma, ixazomib-lenalidomide-dexamethasone (IRd) showed different magnitudes of progression-free survival (PFS) benefit vs placebo-Rd according to number and type of prior therapies, with greater benefit seen in patients with >1 prior line of therapy or 1 prior line of therapy without stem cell transplantation (SCT).

methodsRNA sequencing data were used to investigate the basis of these differences.

resultsThe PFS benefit of IRd vs placebo-Rd was greater in patients with tumors expressing high c-MYC levels (median not reached vs 11.3 months; hazard ratio [HR] 0.42; 95% CI, 0.26, 0.66; P < .001) compared with in those expressing low c-MYC levels (median 20.6 vs 16.6 months; HR 0.75; 95% CI, 0.42, 1.2). Expression of c-MYC in tumors varied based on the number and type of prior therapy received, with the lowest levels observed in tumors of patients who had received 1 prior line of therapy including SCT. These tumors also had higher expression levels of CD19 and CD81.

conclusionsPFS analyses suggest that lenalidomide and ixazomib target tumors with different levels of c-MYC, CD19, and CD81 expression, thus providing a potential rationale for the differential benefits observed in the TOURMALINE-MM1 study. This trial was registered at www.clinicaltrials.gov as: NCT01564537.

Indexed as

Gene ExpressionAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBiomarkers, TumorBoron CompoundsDexamethasoneFemaleGene Expression ProfilingGlycineHumansLenalidomideMaleMiddle AgedMultiple MyelomaNeoplasm GradingBiomarkers, TumorBoron CompoundsDexamethasoneGlycineixazomibLenalidomideProto-Oncogene Proteins c-mycc-myc Proto-Oncogenesmultiple myelomamutationprogression-free survivalRNA sequencing

Identifiers

PMID32145111
PMCPMC7317705
OpenAlexW3010273422

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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.