Evidence map›Paper›PMID 27166360›Full record

Trial reportBlood2016

Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma.

Sarit E Assouline, Torsten Holm Nielsen, Stephen Yu, Miguel Alcaide, Lauren Chong, David MacDonald, Axel Tosikyan, Vishal Kukreti, Abbas Kezouh, Tina Petrogiannis-Haliotis and 14 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01238692 (A Randomized Phase II Study of Oral Panobinostat), which is not on this map. Cited by 77 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 2 pooled it
14.7field-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.

NCT01238692 phase2completednot on this map

A Randomized Phase II Study of Oral Panobinostat (LBH589) With or Without Rituximab to Treat Relapsed or Refractory Diffuse Large B Cell Lymphoma

TypeinterventionalSponsorSarit AssoulineRan2010 to 2016Enrolled42ConditionsDiffuse Large B Cell LymphomaArmsLBH589, Rituximab
3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 2 syntheses or guidelines pooled it, 139 citations in OpenAlex.

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  9. The identification of challenges in tissue collection for biomarker studies: the Q-CROC-03 neoadjuvant breast cancer translational trial experience.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2017
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17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 10 institutions in 1 country.

Sarit E AssoulineSegal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada;
Torsten Holm NielsenSegal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada;
Stephen YuDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada;
Miguel AlcaideDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada;
Lauren ChongCentre for Lymphoid Cancer, Department of Experimental Therapeutics, University of British Columbia, Vancouver, BC, Canada;
David MacDonaldHematology, QEII Health Sciences Centre, Halifax, NS, Canada;
Axel TosikyanDepartement d'oncologie et hematologie, Hopital Sacre-Coeur, Montreal, QC, Canada;
Vishal KukretiMedical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada;
Abbas KezouhDepartment of Oncology and Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada;
Tina Petrogiannis-HaliotisDepartment of Pathology, Jewish General Hospital, Montreal, QC, Canada;
Marco AlbuquerqueDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada;
Daniel FornikaDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada;
Sepideh AlamoutiDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada;
Remi FromentSegal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada;
Celia M T GreenwoodLady Davis Institute, Department of Oncology and Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada;
Kathleen Klein OrosLady Davis Institute, Department of Oncology and Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, QC, Canada;
Errol CamgliogluDepartment of Radiology, Jewish General Hospital, Montreal, QC, Canada;
Ayushi SharmaOzmosis Research, Toronto, ON, Canada;
Rosa ChristodoulopoulosSegal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada;
Caroline RousseauQuebec Clinical Research Organization in Cancer, Montreal, QC, Canada; and.
Nathalie JohnsonSegal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada;
Michael CrumpMedical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada;
Ryan D MorinDepartment of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, BC, Canada; Genome Sciences Centre, BC Cancer Agency, Vancouver, BC, Canada.
Koren K MannSegal Cancer Center, Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada;
Jewish General Hospital · CASimon Fraser University · CAMcGill University · CAPrincess Margaret Cancer Centre · CABC Cancer Agency · CAHealth Sciences Centre · CAHôpital du Sacré-Cœur de Montréal · CAOzmosis Research (Canada) · CAQuebec - Clinical Research Organization in Cancer · CAUniversity of British Columbia · CA

Funding

CIHR 300738
6 · The paper itself

Abstract

The majority of diffuse large B-cell lymphoma (DLBCL) tumors contain mutations in histone-modifying enzymes (HMEs), indicating a potential therapeutic benefit of histone deacetylase inhibitors (HDIs), and preclinical data suggest that HDIs augment the effect of rituximab. In this randomized phase 2 study, we evaluated the response rate and toxicity of panobinostat, a pan-HDI administered 30 mg orally 3 times weekly, with or without rituximab, in 40 patients with relapsed or refractory de novo (n = 27) or transformed (n = 13) DLBCL. Candidate genes and whole exomes were sequenced in relapse tumor biopsies to search for molecular correlates, and these data were used to quantify circulating tumor DNA (ctDNA) in serial plasma samples. Eleven of 40 patients (28%) responded to panobinostat (95% confidence interval [CI] 14.6-43.9) and rituximab did not increase responses. The median duration of response was 14.5 months (95% CI 9.4 to "not reached"). At time of data censoring, 6 of 11 patients had not progressed. Of the genes tested for mutations, only those in MEF2B were significantly associated with response. We detected ctDNA in at least 1 plasma sample from 96% of tested patients. A significant increase in ctDNA at day 15 relative to baseline was strongly associated with lack of response (sensitivity 71.4%, specificity 100%). We conclude that panobinostat induces very durable responses in some patients with relapsed DLBCL, and early responses can be predicted by mutations in MEF2B or a significant change in ctDNA level at 15 days after treatment initiation. This clinical trial was registered at www.ClinicalTrials.gov (#NCT01238692).

Indexed as

AdultAgedDNA, NeoplasmFemaleHumansHydroxamic AcidsIndolesLymphoma, Large B-Cell, DiffuseMaleMEF2 Transcription FactorsMiddle AgedMutationNeoplasm ProteinsPanobinostatRecurrenceRituximabDNA, NeoplasmHydroxamic AcidsIndolesMEF2B protein, humanMEF2 Transcription FactorsNeoplasm ProteinsPanobinostatRituximab

Identifiers

PMID27166360
PMCPMC4972610
OpenAlexW2484616545

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.