Evidence map›Paper›PMID 26338273›Full record

ArticleLeukemia2016

SAR650984 directly induces multiple myeloma cell death via lysosomal-associated and apoptotic pathways, which is further enhanced by pomalidomide.

H Jiang, C Acharya, G An, M Zhong, X Feng, L Wang, N Dasilva, Z Song, G Yang, F Adrian and 5 more

Retracted Registry-linked trialAbstract readRetracted Publication
PubMed Publisher
In one paragraph

Article in Leukemia, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. It is linked to trial NCT04943302 (Isatuximab and Bendamustine in Systemic Light Chain Amyloidosis), which is not on this map. Cited by 120 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
120citing papers in PubMed, 1 pooled it
9.7field-weighted citation impact, top 2% 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.

NCT04943302 phase2withdrawnnot on this mapstarted 2022, after this paper: background citation

Isatuximab and Bendamustine in Systemic Light Chain Amyloidosis

TypeinterventionalSponsorTufts Medical CenterRan2022 to 2026Enrolled0ConditionsAmyloidosis, Light Chain (AL) AmyloidosisArmsBendamustine Hydrochloride, Isatuximab
3 · Its place in the literature

Who cites it

120 citing papers in PubMed, 1 synthesis or guideline pooled it, 221 citations in OpenAlex.

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60 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 2 countries.

H JiangLeBow Institute for Myeloma Therapeutics and the Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
C AcharyaLeBow Institute for Myeloma Therapeutics and the Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
G AnLeBow Institute for Myeloma Therapeutics and the Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
M ZhongLeBow Institute for Myeloma Therapeutics and the Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
X FengLeBow Institute for Myeloma Therapeutics and the Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
L WangLeBow Institute for Myeloma Therapeutics and the Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
N DasilvaLeBow Institute for Myeloma Therapeutics and the Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Z SongSanofi Oncology, Cambridge, MA, USA.
G YangSanofi Oncology, Cambridge, MA, USA.
F AdrianSanofi Oncology, Cambridge, MA, USA.
L QiuInstitute of Hematology, CAMS & PUMC, Tianjin, China.
P RichardsonLeBow Institute for Myeloma Therapeutics and the Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
N C MunshiLeBow Institute for Myeloma Therapeutics and the Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Y-T TaiLeBow Institute for Myeloma Therapeutics and the Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
K C AndersonLeBow Institute for Myeloma Therapeutics and the Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Dana-Farber Cancer Institute · USSanofi (United States) · USInstitute of Hematology & Blood Diseases Hospital · CNSecond Military Medical University · CN

Funding

Trageting the Multiple Myeloma EpigenomeP50CA100707 · NCI · DANA-FARBER CANCER INSTITUTE · PI ANDERSON, KENNETH C., MUNSHI, NIKHIL C. · 2003 to 2023
$45.0M
Targeting Myeloma Cell-Host Bone Marrow InteractionsP01CA078378 · NCI · DANA-FARBER CANCER INSTITUTE · PI RITZ, JEROME · 1998 to 2014
$26.2M
NCI NIH HHS P01-CA078378NCI NIH HHS P50CA100707PHS HHS R01050947
6 · The paper itself

Abstract

The anti-CD38 monoclonal antibody SAR650984 (SAR) is showing promising clinical activity in treatment of relapsed and refractory multiple myeloma (MM). Besides effector-mediated antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity, we here define molecular mechanisms of SAR-directed MM cell death and enhanced anti-MM activity triggered by SAR with Pomalidomide (Pom). Without Fc-cross-linking agents or effector cells, SAR specifically induces homotypic aggregation (HA)-associated cell death in MM cells dependent on the level of cell surface CD38 expression, actin cytoskeleton and membrane lipid raft. SAR and its F(ab)'2 fragments trigger caspase 3/7-dependent apoptosis in MM cells highly expressing CD38, even with p53 mutation. Importantly, SAR specifically induces lysosome-dependent cell death (LCD) by enlarging lysosomes and increasing lysosomal membrane permeabilization associated with leakage of cathepsin B and LAMP-1, regardless of the presence of interleukin-6 or bone marrow stromal cells. Conversely, the lysosomal vacuolar H+-ATPase inhibitor blocks SAR-induced LCD. SAR further upregulates reactive oxygen species. Pom enhances SAR-induced direct and indirect killing even in MM cells resistant to Pom/Len. Taken together, SAR is the first therapeutic monoclonal antibody mediating direct cytotoxicity against MM cells via multiple mechanisms of action. Our data show that Pom augments both direct and effector cell-mediated MM cytotoxicity of SAR, providing the framework for combination clinical trials.

Indexed as

ActinsADP-ribosyl Cyclase 1Antibodies, Monoclonal, HumanizedApoptosisGenes, p53HumansLysosomesMembrane GlycoproteinsMembrane MicrodomainsMultiple MyelomaReactive Oxygen SpeciesThalidomideActinsADP-ribosyl Cyclase 1Antibodies, Monoclonal, HumanizedCD38 protein, humanisatuximabMembrane GlycoproteinspomalidomideReactive Oxygen SpeciesThalidomide

Identifiers

PMID26338273
OpenAlexW1916436059

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.