Evidence map›Paper›PMID 30501868›Full record

Trial reportThe Lancet. Haematology2018

Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement: a prospective, multicentre, single-arm phase 2 study.

Kieron Dunleavy, Michelle A Fanale, Jeremy S Abramson, Ariela Noy, Paolo Fabrizio Caimi, Stefania Pittaluga, Samir Parekh, Ann Lacasce, John W Hayslip, Deepa Jagadeesh and 13 more

2 registry-linked trialsAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Haematology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 122 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
122citing papers in PubMed, 2 pooled it
16.1field-weighted citation impact, top 1% 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.

NCT01092182 phase2completednot on this map

Phase II Study of Dose-Adjusted EPOCH+/-Rituximab in Adults With Untreated Burkitt Lymphoma, c-MYC Positive Diffuse Large B-Cell Lymphoma and Plasmablastic Lymphoma

TypeinterventionalSponsorNational Cancer Institute (NCI)Ran2010 to 2023Enrolled194ConditionsBurkitt Lymphoma, Diffuse Large B-cell Lymphoma, c-MYC Positive, Plasmablastic LymphomaArmsEPOCH-R, EPOCH-RR
NCT04432714 phase1 / phase2recruitingnot on this mapstarted 2020, after this paper: background citation

A Phase II, Prospective, Single-center Study of Lenalidomide in Combination With R-DA-EPOCH in Patients With Untreated DLBCL With MYC Rearrangement

TypeinterventionalSponsorThe First Affiliated Hospital with Nanjing Medical UniversityRan2020 to 2026Enrolled81ConditionsDLBCL, Untreated, MYC Gene RearrangementArmsLenalidomide, Rituximab, Etoposide, Doxorubicin, Vincristine
3 · Its place in the literature

Who cites it

122 citing papers in PubMed, 2 syntheses or guidelines pooled it, 227 citations in OpenAlex.

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62 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors at 14 institutions in 1 country.

Kieron DunleavyLymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Michelle A FanaleMD Anderson Cancer Center, Houston, TX, USA.
Jeremy S AbramsonMassachusetts General Hospital and Dana Farber Cancer Institute, Boston, MA, USA.
Ariela NoyMemorial Sloan Kettering Cancer Center, New York, NY, USA.
Paolo Fabrizio CaimiCase Western Reserve University, Cleveland, Ohio, USA.
Stefania PittalugaHematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Samir ParekhHess Center for Science and Medicine, New York, NY, USA.
Ann LacasceMassachusetts General Hospital and Dana Farber Cancer Institute, Boston, MA, USA.
John W HayslipUniversity of Kentucky, Lexington, KY, USA.
Deepa JagadeeshCleveland Clinic, Cleveland, Ohio, USA.
Sunil NagpalWest Michigan Cancer Center, Kalamazoo, MI, USA.
Mary Jo LechowiczEmory University, Atlanta, GA, USA.
Rakesh GaurSaint Luke's, Kansas City, KS, USA.
Andrea LucasLymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Christopher MelaniLymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Mark RoschewskiLymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD, USA.
Seth M SteinbergCenter for Cancer Research, and Biostatistics and Data Management Section, National Cancer Institute, Bethesda, MD, USA.
Elaine S JaffeHematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA.
Brad KahlWashington University, St Louis, MO, USA.
Jonathan W FriedbergUniversity of Rochester, Rochester, NY, USA.
Richard F LittleCancer and Therapeutic Evaluation Program, National Cancer Institute, Bethesda, MD, USA.
Nancy L BartlettWashington University, St Louis, MO, USA.
Wyndham H WilsonLymphoid Malignancies Branch, National Cancer Institute, Bethesda, MD, USA. Electronic address: wilsonw@mail.nih.gov.
National Cancer Institute · USWashington University in St. Louis · USCase Western Reserve University · USCleveland Clinic · USDana-Farber Cancer Institute · USEmory University · USHess (United States) · USMassachusetts General Hospital · USMemorial Sloan Kettering Cancer Center · USSaint Luke's Hospital · USThe University of Texas MD Anderson Cancer Center · USUniversity of Kentucky · USUniversity of Rochester · USWest Michigan Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
SWOG Network Group Operations Center of the NCTNU10CA180888 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI PRIMO N. LARA · 2014 to 2026
$152.1M
Hematopathology DiagnosisZIABC011070 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI JAFFE, ELAINE · 2009 to 2025
$14.5M
Therapeutic Strategies and Molecular Correlates in Aggressive B-cell LymphomasZIASC006741 · NCI · DIVISION OF CLINICAL SCIENCES - NCI · PI WILSON, WYNDHAM H · 2009 to 2025
$10.4M
LYMPHOMA STUDIESZ01SC006741 · SC · DIVISION OF CLINICAL SCIENCES - NCI · PI WILSON, WYNDHAM H · 1996 to 2008
$893k
Intramural NIH HHS Z01 SC006741NCI NIH HHS P30 CA008748NCI NIH HHS U10 CA180888
6 · The paper itself

Abstract

backgroundMYC gene rearrangement is present in approximately 10% of aggressive B-cell lymphomas, with half also harbouring a BCL2 gene rearrangement. Multiple retrospective studies of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone or prednisolone) have shown a worse outcome in patients with MYC rearrangement (alone or with rearrangement of BCL2 or BCL6, or both) than in patients without MYC rearrangement, and suggest improved outcomes after more intensive treatment. We aimed to determine the outcome of dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; DA-EPOCH-R), an intensive infusional treatment regimen, in untreated aggressive B-cell lymphoma with MYC rearrangement.

methodsWe present the final analysis of a prospective, multicentre, single-arm, phase 2 study of DA-EPOCH-R in patients with untreated aggressive B-cell lymphoma with MYC rearrangement. DA-EPOCH-R was scheduled to be administered with CNS prophylaxis for six cycles. Primary endpoints included event-free and overall survival. This study is registered with ClinicalTrials.gov (NCT01092182).

findings53 patients were enrolled, with median age of 61 years (range 29-80; IQR 50-70); 43 (81%) patients had stage III-IV disease and 26 (49%) had high-intermediate or high international prognostic index (IPI) scores. 19 patients had confirmed MYC rearrangement alone (single-hit) and 24 also had rearrangement of BCL2, BCL6, or both (double-hit), with similar characteristics between these two groups. After a median follow-up of 55·6 months (IQR 50·5-61·1), 48-month event-free survival was 71·0% (95% CI 56·5-81·4) and 48-month overall survival was 76·7% (95% CI 62·6-86·1) for all patients. Toxicity included grade 4 neutropenia in 160 (53%) of 301 cycles, grade 4 thrombocytopenia in 40 (13%) cycles, and any grade of fever with neutropenia in 56 (19%) cycles. There were three treatment-related deaths (all infections).

interpretationIn this study, DA-EPOCH-R produced durable remission in patients with MYC-rearranged aggressive B-cell lymphomas and should be considered for the treatment of these diseases.

fundingCancer Trials Support Unit and Center for Cancer Research of the National Cancer Institute and Genentech.

Indexed as

Gene RearrangementAdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsCyclophosphamideDose-Response Relationship, DrugDoxorubicinEtoposideFemaleHumansLymphoma, Large B-Cell, DiffuseMaleMiddle AgedPrednisoneProto-Oncogene Proteins c-mycCyclophosphamideDoxorubicinEtoposideMYC protein, humanPrednisoneProto-Oncogene Proteins c-mycRituximabVincristine

Identifiers

PMID30501868
PMCPMC6342507
OpenAlexW2902608107

What OpenQuestion holds

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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.