Evidence map›Paper›PMID 31109827›Full record

ArticleThe Lancet. Haematology2019

Prognostic risk score for patients with relapsed or refractory chronic lymphocytic leukaemia treated with targeted therapies or chemoimmunotherapy: a retrospective, pooled cohort study with external validations.

Jacob D Soumerai, Ai Ni, Mohamed Darif, Anil Londhe, Guan Xing, Yong Mun, Neil E Kay, Tait D Shanafelt, Kari G Rabe, John C Byrd and 15 more

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

Article in The Lancet. Haematology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04560322 (A Phase 2 Study of MRD Adapted Therapy With Venetoclax-obinutuzumab in Patients With High or Intermediate BALL Risk Relapsed or Refractory CLL, With Addition of Acalabrutinib in Patients Who Fail to Achieve MRD Eradication), which is not on this map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
6.3field-weighted citation impact, top 3% 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.

NCT04560322 phase2recruitingnot on this mapstarted 2020, after this paper: background citation

A Phase 2 Study of MRD Adapted Therapy With Venetoclax-obinutuzumab in Patients With High or Intermediate BALL Risk Relapsed or Refractory CLL, With Addition of Acalabrutinib in Patients Who Fail to Achieve MRD Eradication

TypeinterventionalSponsorMassachusetts General HospitalRan2020 to 2029Enrolled40ConditionsChronic Lymphocytic Leukemia, Small Lymphocytic LymphomaArmsVenetoclax, Obinutuzumab, Acalabrutinib
3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.

  1. Pooled it
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  16. Efficacy and Safety of Ibrutinib Therapy in Patients with Chronic Lymphocytic Leukemia: Retrospective Analysis of Real-Life DataTurkish journal of haematology : official journal of Turkish Society of Haematology · 2021
    Article
  17. Review
  18. The Chronic Lymphocytic Leukemia Comorbidity Index (CLL-CI): A Three-Factor Comorbidity Model.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
  19. Clinical Outcomes in Patients with Multi-HitClinical cancer research : an official journal of the American Association for Cancer Research · 2021
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

25 authors at 13 institutions in 3 countries.

Jacob D SoumeraiMassachusetts General Hospital Cancer Center, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Memorial-Sloan Kettering Cancer Center, New York, NY, USA. Electronic address: jsoumerai@mgh.harvard.edu.
Ai NiMemorial-Sloan Kettering Cancer Center, New York, NY, USA.
Mohamed DarifJanssen Pharmaceuticals, Horsham, PA, USA.
Anil LondheJanssen Pharmaceuticals, Horsham, PA, USA.
Guan XingGilead Sciences, Seattle, WA, USA.
Yong MunGenentech, South San Francisco, CA, USA.
Neil E KayMayo Clinic, Rochester, MN, USA.
Tait D ShanafeltMayo Clinic, Rochester, MN, USA; Stanford University Medical Center, Stanford, CA, USA.
Kari G RabeMayo Clinic, Rochester, MN, USA.
John C ByrdOhio State University Comprehensive Cancer Center, Columbus, OH, USA.
Asher A Chanan-KhanMayo Clinic, Jacksonville, FL, USA.
Richard R FurmanWeill Cornell Medical College/New York Presbyterian Hospital, New York, NY, USA.
Peter HillmenSt James's University Hospital, Leeds, UK.
Jeffrey JonesOhio State University Comprehensive Cancer Center, Columbus, OH, USA.
John F SeymourPeter MacCallum Cancer Centre, Royal Melbourne Hospital, The University of Melbourne, Melbourne, VIC, Australia.
Jeffrey P SharmanWillamette Valley Cancer Institute and Research Center, Eugene, OR, USA.
Lucille FerranteJanssen Pharmaceuticals, Horsham, PA, USA.
Mehrdad MobasherGenentech, South San Francisco, CA, USA.
Thomas StarkGenentech, South San Francisco, CA, USA.
Vijay ReddyPharmacyclics, Sunnyvale, CA, USA.
Lyndah K DreilingGilead Sciences, Seattle, WA, USA.
Pankaj BhargavaGilead Sciences, Seattle, WA, USA.
Angela HowesJanssen Pharmaceuticals, Horsham, PA, USA.
Danelle F JamesMemorial-Sloan Kettering Cancer Center, New York, NY, USA.
Andrew D ZelenetzMemorial-Sloan Kettering Cancer Center, New York, NY, USA.
Janssen (United States) · USGilead Sciences (United States) · USMemorial Sloan Kettering Cancer Center · USMayo Clinic in Arizona · USThe Ohio State University · USMassachusetts General Hospital · USMayo Clinic in Florida · USPharmacyclics (United States) · USPresbyterian Hospital · USStanford University · USSt James's University Hospital · GBThe Royal Melbourne Hospital · AUWillamette Valley Cancer Institute and Research Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
NCI NIH HHS P30 CA008748
6 · The paper itself

Abstract

backgroundClinically validated prognostic models for overall survival do not exist for patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) who are on targeted therapies. We aimed to create a prognostic model to identify high-risk individuals who do not achieve a good outcome with available targeted therapies.

methodsIn this retrospective, pooled cohort study, 2475 patients with CLL treated between June 22, 2012, and Sept 23, 2015, in six randomised trials of ibrutinib, idelalisib, and venetoclax, or at the Mayo Clinic CLL Database (MCCD) were included. Eligible patients had CLL, were previously treated, were aged 18 years or older, had ECOG performance status 0-1, and required further treatment as per the international workshop on CLL 2008 criteria. There was heterogeneity in other eligibility criteria. We evaluated 28 candidate factors known to affect the overall survival of these patients and applied univariate and multivariate analyses to derive the risk score in a training dataset (n=727) of patients treated with ibrutinib or chemoimmunotherapy. We validated the score in an internal-validation dataset (n=242) of patients treated with ibrutinib or chemoimmunotherapy and three external-validation datasets (idelalisib or chemoimmunotherapy dataset, n=897; venetoclax or chemoimmunotherapy dataset, n=389; and the MCCD [including patients treated with heterogeneous therapies], n=220), applying C-statistics as a measure of discrimination.

findingsThe derived model consisted of four factors (one point each; serum β

interpretationWe present the first validated risk score to predict overall survival in patients with relapsed or refractory CLL treated with targeted therapy. The model is applicable to patients treated with all currently approved targeted therapies (ibrutinib, idelalisib, and venetoclax) and chemoimmunotherapy. This tool allows the identification of a well defined cohort of previously treated patients with CLL who are at high risk of death, and could be used in future prospective trials to test therapeutic options for these patients with an unmet clinical need.

fundingLymphoma Research Foundation, Lymphoma Research Fund (Andrew D Zelenetz), and National Institutes of Health/National Cancer Institute.

Indexed as

ImmunotherapyAdenineAntineoplastic Agentsbeta 2-MicroglobulinBridged Bicyclo Compounds, HeterocyclicDatabases, FactualFemaleHemoglobinsHumansLeukemia, Lymphocytic, Chronic, B-CellL-Lactate DehydrogenaseMaleMiddle AgedPiperidinesPrognosisProportional Hazards ModelsAdenineAntineoplastic Agentsbeta 2-MicroglobulinBridged Bicyclo Compounds, HeterocyclicHemoglobinsibrutinibidelalisibL-Lactate DehydrogenasePiperidinesPurinesPyrazolesPyrimidinesQuinazolinonesSulfonamidesvenetoclax

Identifiers

PMID31109827
PMCPMC6620111
OpenAlexW2944976872

What OpenQuestion holds

Textmetadata
LicenceTDM
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.