Evidence map›Paper›PMID 28418267›Full record

Trial reportJournal of clinical oncology : official journal of the American Society of Clinical Oncology2017

BTK

Jennifer A Woyach, Amy S Ruppert, Daphne Guinn, Amy Lehman, James S Blachly, Arletta Lozanski, Nyla A Heerema, Weiqiang Zhao, Joshua Coleman, Daniel Jones and 22 more

Abstract readClinical Trial, Phase IClinical Trial, Phase IIClinical Trial, Phase III
In one paragraph

Trial report in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 277 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
277citing papers in PubMed, 2 pooled it
25.7field-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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

277 citing papers in PubMed, 2 syntheses or guidelines pooled it, 466 citations in OpenAlex.

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  8. Adding Umbralisib and Ublituximab (U2) to Ibrutinib in Patients with CLL: A Phase II Study of an MRD-Driven Approach.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022
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217 more citing papers are in PubMed but not listed here.

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

32 authors at 1 institution in 1 country.

Jennifer A WoyachAll authors: The Ohio State University, Columbus, OH.
Amy S RuppertAll authors: The Ohio State University, Columbus, OH.
Daphne GuinnAll authors: The Ohio State University, Columbus, OH.
Amy LehmanAll authors: The Ohio State University, Columbus, OH.
James S BlachlyAll authors: The Ohio State University, Columbus, OH.
Arletta LozanskiAll authors: The Ohio State University, Columbus, OH.
Nyla A HeeremaAll authors: The Ohio State University, Columbus, OH.
Weiqiang ZhaoAll authors: The Ohio State University, Columbus, OH.
Joshua ColemanAll authors: The Ohio State University, Columbus, OH.
Daniel JonesAll authors: The Ohio State University, Columbus, OH.
Lynne AbruzzoAll authors: The Ohio State University, Columbus, OH.
Amber GordonAll authors: The Ohio State University, Columbus, OH.
Rose MantelAll authors: The Ohio State University, Columbus, OH.
Lisa L SmithAll authors: The Ohio State University, Columbus, OH.
Samantha McWhorterAll authors: The Ohio State University, Columbus, OH.
Melanie DavisAll authors: The Ohio State University, Columbus, OH.
Tzyy-Jye DoongAll authors: The Ohio State University, Columbus, OH.
Fan NyAll authors: The Ohio State University, Columbus, OH.
Margaret LucasAll authors: The Ohio State University, Columbus, OH.
Weihong ChaseAll authors: The Ohio State University, Columbus, OH.
Jeffrey A JonesAll authors: The Ohio State University, Columbus, OH.
Joseph M FlynnAll authors: The Ohio State University, Columbus, OH.
Kami MaddocksAll authors: The Ohio State University, Columbus, OH.
Kerry RogersAll authors: The Ohio State University, Columbus, OH.
Samantha JaglowskiAll authors: The Ohio State University, Columbus, OH.
Leslie A AndritsosAll authors: The Ohio State University, Columbus, OH.
Farrukh T AwanAll authors: The Ohio State University, Columbus, OH.
Kristie A BlumAll authors: The Ohio State University, Columbus, OH.
Michael R GreverAll authors: The Ohio State University, Columbus, OH.
Gerard LozanskiAll authors: The Ohio State University, Columbus, OH.
Amy J JohnsonAll authors: The Ohio State University, Columbus, OH.
John C ByrdAll authors: The Ohio State University, Columbus, OH.
The Ohio State University · US

Funding

Women's Cancer Research ProgramP30CA014236 · NCI · DUKE UNIVERSITY · PI JOHN N. NORTON · 1985 to 2026
$174.8M
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
TWO SIGNAL REQUIREMENT FOR NATURAL KILLER IMMUNITYP01CA095426 · NCI · OHIO STATE UNIVERSITY · PI CALIGIURI, MICHAEL A · 2002 to 2016
$29.6M
SPORE Leukemia Tissue BankP50CA140158 · NCI · OHIO STATE UNIVERSITY · PI MARCUCCI, GUIDO · 2009 to 2013
$11.2M
Targeted Therapy for LeukemiaR35CA197734 · NCI · UNIVERSITY OF CINCINNATI · PI BYRD, JOHN C. · 2015 to 2021
$6.6M
Targeted Therapy for Lymphoid MalignanciesR01CA177292 · NCI · OHIO STATE UNIVERSITY · PI ROGERS, KERRY ANNE, WOYACH, JENNIFER A. · 2013 to 2025
$5.3M
Molecular Evaluation of Targeted Therapies in Lymphoid MalignanciesR01CA183444 · NCI · OHIO STATE UNIVERSITY · PI BYRD, JOHN C., WOYACH, JENNIFER A. · 2014 to 2018
$2.6M
Improving BTK Directed Therapy for CLLR01CA197870 · NCI · OHIO STATE UNIVERSITY · PI WOYACH, JENNIFER A. · 2015 to 2019
$1.8M
Targeted Therapies and Mechanisms of Resistance in Chronic Lymphocytic LeukemiaK23CA178183 · NCI · OHIO STATE UNIVERSITY · PI WOYACH, JENNIFER A. · 2013 to 2017
$866k
NCI NIH HHS K23 CA178183NCI NIH HHS P01 CA095426NCI NIH HHS P30 CA014236NCI NIH HHS P30 CA016058NCI NIH HHS P50 CA140158NCI NIH HHS R01 CA177292NCI NIH HHS R01 CA183444NCI NIH HHS R01 CA197870NCI NIH HHS R35 CA197734
6 · The paper itself

Abstract

Purpose Therapeutic targeting of Bruton tyrosine kinase (BTK) with ibrutinib in chronic lymphocytic leukemia has led to a paradigm shift in therapy, and relapse has been uncommon with current follow-up. Acquired mutations in BTK and PLCG2 can cause relapse, but data regarding the prevalence and natural history of these mutations are limited. Patients and Methods Patients accrued to four sequential studies of ibrutinib were included in these analyses. Deep sequencing for BTK and PLCG2 was performed retrospectively on patients who experienced relapse and prospectively on a screening population. Results With a median follow-up time of 3.4 years, the estimated cumulative incidence of progression at 4 years is 19% (95% CI, 14% to 24%). Baseline karyotypic complexity, presence of del(17)(p13.1), and age less than 65 years were risk factors for progression. Among patients who experienced relapse, acquired mutations of BTK or PLCG2 were found in 85% (95% CI, 71% to 94%), and these mutations were detected an estimated median of 9.3 months (95% CI, 7.6 to 11.7 months) before relapse. Of a group of 112 patients examined prospectively, eight patients have experienced relapse, and all of these patients had acquired resistance mutations before relapse. A resistance mutation was detected in an additional eight patients who have not yet met criteria for clinical relapse. Conclusion Relapse of chronic lymphocytic leukemia after ibrutinib is an issue of increasing clinical significance. We show that mutations in BTK and PLCG2 appear early and have the potential to be used as a biomarker for future relapse, suggesting an opportunity for intervention.

Indexed as

AdenineAdultAgammaglobulinaemia Tyrosine KinaseAgedAged, 80 and overAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsDrug Resistance, NeoplasmHumansLeukemia, Lymphocytic, Chronic, B-CellMaleMiddle AgedPhospholipase C gammaPiperidinesProtein-Tyrosine KinasesAdenineAgammaglobulinaemia Tyrosine KinaseAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedBTK protein, humanibrutinibofatumumabPhospholipase C gammaPiperidinesProtein-Tyrosine KinasesPyrazolesPyrimidines

Identifiers

PMID28418267
PMCPMC5455463
OpenAlexW2589238872

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.