Evidence map›Paper›PMID 28017967›Full record

ArticleLeukemia2017

Duvelisib treatment is associated with altered expression of apoptotic regulators that helps in sensitization of chronic lymphocytic leukemia cells to venetoclax (ABT-199).

V M Patel, K Balakrishnan, M Douglas, T Tibbitts, E Y Xu, J L Kutok, M Ayers, A Sarkar, R Guerrieri, W G Wierda and 4 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Leukemia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02640833 (A Phase 1b/2 Study of Duvelisib and Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Indolent or Aggressive Non-Hodgkin Lymphoma, Who Have Not Previously Received a Bcl-2 or PI3K Inhibitor), which is not on this map. Cited by 40 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 2 pooled it
5.4field-weighted citation impact, top 4% 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.

NCT02640833 phase1withdrawnnot on this map

A Phase 1b/2 Study of Duvelisib and Venetoclax in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, or Indolent or Aggressive Non-Hodgkin Lymphoma, Who Have Not Previously Received a Bcl-2 or PI3K Inhibitor

TypeinterventionalSponsorAbbVieRan2016 to 2021Enrolled0ConditionsChronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma, Non-Hodgkin LymphomaArmsDuvelisib, Venetoclax
3 · Its place in the literature

Who cites it

40 citing papers in PubMed, 2 syntheses or guidelines pooled it, 66 citations in OpenAlex.

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  9. Dual mTORC1/2 Inhibition Synergistically Enhances AML Cell Death in Combination with the BCL2 Antagonist Venetoclax.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023
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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

14 authors at 2 institutions in 1 country.

V M PatelDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
K BalakrishnanDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
M DouglasInfinity Pharmaceuticals Inc., Cambridge, MA, USA.
T TibbittsInfinity Pharmaceuticals Inc., Cambridge, MA, USA.
E Y XuInfinity Pharmaceuticals Inc., Cambridge, MA, USA.
J L KutokInfinity Pharmaceuticals Inc., Cambridge, MA, USA.
M AyersDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
A SarkarDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
R GuerrieriDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
W G WierdaDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
S O'BrienDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
N JainDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
H M SternInfinity Pharmaceuticals Inc., Cambridge, MA, USA.
V GandhiDepartment of Experimental Therapeutics, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
The University of Texas MD Anderson Cancer Center · USInfinity Pharmaceuticals (United States) · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8M
Tissue CoreP01CA081534 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI KIPPS, THOMAS J · 2000 to 2016
$59.5M
NCI NIH HHS P01 CA081534NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

Duvelisib, an oral dual inhibitor of PI3K-δ and PI3K-γ, is in phase III trials for the treatment of chronic lymphocytic leukemia (CLL) and indolent non-Hodgkin's lymphoma. In CLL, duvelisib monotherapy is associated with high iwCLL (International Workshop on Chronic Lymphocytic Leukemia) and nodal response rates, but complete remissions are rare. To characterize the molecular effect of duvelisib, we obtained samples from CLL patients on the duvelisib phase I trial. Gene expression studies (RNAseq, Nanostring, Affymetrix array and real-time RT-PCR) demonstrated increased expression of BCL2 along with several BH3-only pro-apoptotic genes. In concert with induction of transcript levels, reverse phase protein arrays and immunoblots confirmed increase at the protein level. The BCL2 inhibitor venetoclax induced greater apoptosis in ex vivo-cultured CLL cells obtained from patients on duvelisib compared with pre-treatment CLL cells from the same patients. In vitro combination of duvelisib and venetoclax resulted in enhanced apoptosis even in CLL cells cultured under conditions that simulate the tumor microenvironment. These data provide a mechanistic rationale for testing the combination of duvelisib and venetoclax in the clinic. Such combination regimen (NCT02640833) is being evaluated for patients with B-cell malignancies including CLL.

Indexed as

Antineoplastic AgentsApoptosisApoptosis Regulatory ProteinsBridged Bicyclo Compounds, HeterocyclicDrug SynergismHumansIsoquinolinesLeukemia, Lymphocytic, Chronic, B-CellPurinesSulfonamidesTumor Cells, CulturedAntineoplastic AgentsApoptosis Regulatory ProteinsBridged Bicyclo Compounds, HeterocyclicduvelisibIsoquinolinesPurinesSulfonamidesvenetoclax

Identifiers

PMID28017967
PMCPMC5540815
OpenAlexW2563723939

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.