Evidence map›Paper›PMID 35027656›Full record

Trial reportLeukemia2022

Cell-free DNA for the detection of emerging treatment failure in relapsed/ refractory multiple myeloma.

Johannes M Waldschmidt, Andrew J Yee, Tushara Vijaykumar, Ricardo A Pinto, Julia Frede, Praveen Anand, Giada Bianchi, Guangwu Guo, Sayalee Potdar, Charles Seifer and 18 more

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

Trial report in Leukemia, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02718833 (A Phase II Study of Elotuzumab in Combination With Pomalidomide, Bortezomib, and Dexamethasone in Relapsed and Refractory Multiple Myeloma), which is not on this map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
4.2field-weighted citation impact, top 5% 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.

NCT02718833 phase2active not recruitingnot on this map

A Phase II Study of Elotuzumab in Combination With Pomalidomide, Bortezomib, and Dexamethasone in Relapsed and Refractory Multiple Myeloma

TypeinterventionalSponsorMassachusetts General HospitalRan2016 to 2027Enrolled52ConditionsMultiple MyelomaArmsElotuzumab, Pomalidomide, Bortezomib, Dexamethasone
3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.

  1. Pooled it
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  16. Response-Adapted Therapy for Newly Diagnosed Multiple Myeloma.Current hematologic malignancy reports · 2023
    Review
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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

28 authors at 7 institutions in 1 country.

Johannes M Waldschmidt *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Andrew J Yee *Harvard Medical School, Boston, MA, USA.
Tushara Vijaykumar *Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Ricardo A PintoBroad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9175-1357
Julia FredeDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-4380-9673
Praveen AnandDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Giada BianchiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0003-3673-0104
Guangwu GuoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Sayalee PotdarDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-5390-1222
Charles SeiferDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Monica S NairDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Antonis KokkalisDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7779-0600
Jake A KloeberDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6646-564X
Samantha ShapiroMassachusetts General Hospital, Boston, MA, USA.
Lillian BudanoMassachusetts General Hospital, Boston, MA, USA.
Mason MannMassachusetts General Hospital, Boston, MA, USA.
Robb FriedmanNewton Wellesley Hospital, Newton, MA, USA.
Brea LipeUniversity of Rochester, Rochester, NY, USA.
Erica CampagnaroUniversity of Michigan, Ann Arbor, MI, USA.
Elizabeth K O'DonnellHarvard Medical School, Boston, MA, USA.
Cheng-Zhong ZhangBroad Institute of MIT and Harvard, Cambridge, MA, USA.
Jacob P LaubachDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0001-7565-2052
Nikhil C MunshiDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7344-9795
Paul G RichardsonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-7426-8865
Kenneth C AndersonDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6418-0886
Noopur S RajeHarvard Medical School, Boston, MA, USA.
Birgit KnoechelHarvard Medical School, Boston, MA, USA.ORCID http://orcid.org/0000-0002-8040-0535
Jens G LohrDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. jensg_lohr@dfci.harvard.edu.ORCID http://orcid.org/0000-0003-3486-2445
Broad Institute · USHarvard University · USDana-Farber Cancer Institute · USMassachusetts General Hospital · USNewton Wellesley Hospital · USUniversity of Michigan · USUniversity of Rochester · US

Funding

Determining the mutational landscape of circulating multiple myeloma cellsK08CA191026 · NCI · DANA-FARBER CANCER INST · PI LOHR, JENS G · 2015 to 2019
$886k
Epigenetic mechanisms of drug resistance in T-cell acute lymphoblastic leukemiaK08CA191091 · NCI · DANA-FARBER CANCER INST · PI KNOECHEL, BIRGIT · 2015 to 2019
$886k
NCI NIH HHS K08 CA191026NCI NIH HHS K08 CA191091
6 · The paper itself

Abstract

Interrogation of cell-free DNA (cfDNA) represents an emerging approach to non-invasively estimate disease burden in multiple myeloma (MM). Here, we examined low-pass whole genome sequencing (LPWGS) of cfDNA for its predictive value in relapsed/ refractory MM (RRMM). We observed that cfDNA positivity, defined as ≥10% tumor fraction by LPWGS, was associated with significantly shorter progression-free survival (PFS) in an exploratory test cohort of 16 patients who were actively treated on diverse regimens. We prospectively determined the predictive value of cfDNA in 86 samples from 45 RRMM patients treated with elotuzumab, pomalidomide, bortezomib, and dexamethasone in a phase II clinical trial (NCT02718833). PFS in patients with tumor-positive and -negative cfDNA after two cycles of treatment was 1.6 and 17.6 months, respectively (HR 7.6, P < 0.0001). Multivariate hazard modelling confirmed cfDNA as independent risk factor (HR 96.6, P = 6.92e-05). While correlating with serum-free light chains and bone marrow, cfDNA additionally discriminated patients with poor PFS among those with the same response by IMWG criteria. In summary, detectability of MM-derived cfDNA, as a measure of substantial tumor burden with therapy, independently predicts poor PFS and may provide refinement for standard-of-care response parameters to identify patients with poor response to treatment earlier than is currently feasible.

Indexed as

Cell-Free Nucleic AcidsMultiple MyelomaHumansTreatment FailureCell-Free Nucleic Acids

Identifiers

PMID35027656
PMCPMC8983453
OpenAlexW4206265563

What OpenQuestion holds

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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.