Evidence map›Paper›PMID 25596266›Full record

Trial reportHaematologica2015

The genotype of MLH1 identifies a subgroup of follicular lymphoma patients who do not benefit from doxorubicin: FIL-FOLL study.

Davide Rossi, Alessio Bruscaggin, Piera La Cava, Sara Galimberti, Elena Ciabatti, Stefano Luminari, Luigi Rigacci, Alessandra Tucci, Alessandro Pulsoni, Giovanni Bertoldero and 10 more

Registry-linked trialOpen access · goldAbstract readClinical TrialMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in Haematologica, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00774826 (Phase III Multicentric IIL Study, Three Randomized Arms), which is not on this map. Cited by 4 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 2 pooled it
0.4field-weighted citation impact, top 34% 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.

NCT00774826 phase3unknown statusnot on this map

Phase III Multicentric IIL Study, Three Randomized Arms (R-CVP vs R-CHOP vs R-FM),for Treatment of Patients With Stage II-IV Follicular Lymphoma

TypeinterventionalSponsorFondazione Italiana Linfomi - ETSRan2005 to 2014Enrolled534ConditionsFollicular LymphomaArmsR-CVP, R-CHOP, R-FM
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 2 syntheses or guidelines pooled it, 7 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
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

20 authors at 12 institutions in 2 countries.

Davide RossiDivision of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara.
Alessio BruscagginDivision of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara.
Piera La CavaDivision of Hematology, AOU "Policlinico V. Emanuele", Catania.
Sara GalimbertiDepartment of Oncology, Transplants and Advanced Technologies, Section of Haematology, University of Pisa.
Elena CiabattiDepartment of Oncology, Transplants and Advanced Technologies, Section of Haematology, University of Pisa.
Stefano LuminariDepartment of Oncology and Hematology, University of Modena and Reggio Emilia, Modena.
Luigi RigacciDivision of Hematology, Azienda Ospedaliero Universitaria Careggi, Florence.
Alessandra TucciDivision of Hematology, Spedali Civili Hospital and University, Brescia.
Alessandro PulsoniHematology, Department of Cellular Biotechnologies and Hematology, Sapienza University, Rome.
Giovanni BertolderoDepartment of Oncology, Civic Hospital, Noale, Venice.
Daniele VallisaDivision of Hematology, Ospedale Civile, Piacenza.
Chiara RusconiDivision of Hematology, Department of Hematology and Oncology, Niguarda Hospital, Milan.
Michele SpinaDivision of Medical Oncology A, National Cancer Institute, Aviano.
Luca ArcainiDivisions of Hematology, Fondazione IRCCS Policlinico San Matteo, University of Pavia.
Francesco AngrilliDepartment of Hematology, Local Health Unit of Pescara.
Caterina StelitanoDivision of Hematology, Ospedale di Reggio Calabria.
Francesco MerliHematology Unit, Arcispedale Santa Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy.
Gianluca GaidanoDivision of Hematology, Department of Translational Medicine, Amedeo Avogadro University of Eastern Piedmont, Novara.
Massimo FedericoDepartment of Oncology and Hematology, University of Modena and Reggio Emilia, Modena.
Giuseppe A PalumboDivision of Hematology, AOU "Policlinico V. Emanuele", Catania palumbo.ga@gmail.com.
Università degli Studi del Piemonte Orientale “Amedeo Avogadro” · ITUniversity of Modena and Reggio Emilia · ITUniversity of Pisa · ITAzienda Ospedaliero-Universitaria Careggi · ITAzienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · ITAzienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda · ITAzienda USL di Pescara · ITNational Cancer Institute · UAOspedale Santa Maria · ITPoliclinico San Matteo Fondazione · ITSapienza University of Rome · ITUniversity of Reggio Calabria · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Though most follicular lymphoma biomarkers rely on tumor features, the host genetic background may also be relevant for outcome. Here we aimed at verifying the contribution of candidate polymorphisms of FCγ receptor, DNA repair and detoxification genes to prognostic stratification of follicular lymphoma treated with immunochemotherapy. The study was based on 428 patients enrolled in the FOLL05 prospective trial that compared three standard-of-care regimens (rituximab-cyclophosphamide-vincristine-prednisone versus rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone versus rituximab-fludarabine-mitoxantrone) for the first line therapy of advanced follicular lymphoma. Polymorphisms were genotyped on peripheral blood DNA samples. The primary endpoint was time to treatment failure. Polymorphisms of FCGR2A and FCGR3A, which have been suggested to influence the activity of rituximab as a single agent, did not affect time to treatment failure in the pooled analysis of the three FOLL05 treatment arms that combined rituximab with chemotherapy (P=0.742, P=0.252, respectively). These results were consistent even when the analysis was conducted by intention to treat, indicating that different chemotherapy regimens and loads did not interact differentially with the FCGR2A and FCGR3A genotypes. The genotype of MLH1, which regulates the genotoxic effect of doxorubicin, significantly affected time to treatment failure in patients in the rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone arm (P=0.001; q<0.1), but not in arms in which patients did not receive doxorubicin (i.e., the rituximab-cyclophosphamide-vincristine-prednisone and rituximab-fludarabine-mitoxantrone arms). The impact of MLH1 on time to treatment failure was independent after adjusting for the Follicular Lymphoma International Prognostic Index and other potential confounding variables by multivariate analysis. These data indicate that MLH1 genotype is a predictor of failure to benefit from rituximab-cyclophosphamide-doxorubicin-vincristine-prednisone treatment in advanced follicular lymphoma and confirm that FCGR2A and FCGR3A polymorphisms have no impact when follicular lymphoma is treated with rituximab plus chemotherapy (clinicaltrials.gov identifier: NCT00774826).

Indexed as

GenotypeAdaptor Proteins, Signal TransducingAgedAntibiotics, AntineoplasticAntineoplastic Combined Chemotherapy ProtocolsDoxorubicinFemaleHumansKaplan-Meier EstimateLymphoma, FollicularMaleMiddle AgedMutL Protein Homolog 1Neoplasm GradingNeoplasm MetastasisNeoplasm StagingAdaptor Proteins, Signal TransducingAntibiotics, AntineoplasticDoxorubicinMLH1 protein, humanMutL Protein Homolog 1Nuclear ProteinsReceptors, IgG

Identifiers

PMID25596266
PMCPMC4380725
OpenAlexW2043020294

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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.