Evidence map›Paper›PMID 30060083›Full record

ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2018

Venetoclax, bendamustine, and rituximab in patients with relapsed or refractory NHL: a phase Ib dose-finding study.

S de Vos, L J Swinnen, D Wang, E Reid, N Fowler, J Cordero, M Dunbar, S H Enschede, C Nolan, A M Petrich and 8 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01594229 (A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Combination With Bendamustine/Rituximab), which is not on this map. Cited by 45 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed, 1 pooled it
7.6field-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.

NCT01594229 phase1completednot on this map

A Phase 1 Study Evaluating the Safety and Pharmacokinetics of ABT-199 in Combination With Bendamustine/Rituximab (BR) in Subjects With Relapsed or Refractory Non-Hodgkin's Lymphoma

TypeinterventionalSponsorAbbVieRan2012 to 2020Enrolled60ConditionsNon-Hodgkin's LymphomaArmsABT-199, Rituximab, Bendamustine
3 · Its place in the literature

Who cites it

45 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Pooled it
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  6. Targeting protein-protein interactions in the BCL-2 family: opportunities for precision oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
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  19. Expression of NBioengineered · 2021
    Article
  20. BH3-mimetics: recent developments in cancer therapy.Journal of experimental & clinical cancer research : CR · 2021
    Review
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

18 authors at 9 institutions in 2 countries.

S de VosDavid Geffen School of Medicine at UCLA, Los Angeles. Electronic address: deVos@mednet.ucla.edu.
L J SwinnenDivision of Hematologic Malignancies, Department of Oncology, Johns Hopkins University, Baltimore.
D WangDivision of Hematology/Oncology, Department of Medicine, Henry Ford Hospital, Detroit.
E ReidDivision of Hematology-Oncology, Moores Cancer Center, University of California San Diego, La Jolla.
N FowlerDepartment of Lymphoma/Myeloma, University of Texas MD Anderson Cancer Center, Houston.
J CorderoAbbVie Inc., North Chicago, USA.
M DunbarAbbVie Inc., North Chicago, USA.
S H EnschedeAbbVie Inc., North Chicago, USA.
C NolanAbbVie Inc., North Chicago, USA.
A M PetrichAbbVie Inc., North Chicago, USA.
J A RossAbbVie Inc., North Chicago, USA.
A H SalemAbbVie Inc., North Chicago, USA; Ain Shams University, Cairo, Egypt.
M VerdugoAbbVie Inc., North Chicago, USA.
S AgarwalAbbVie Inc., North Chicago, USA.
L ZhouAbbVie Inc., North Chicago, USA.
M KozloffDepartment of Oncology, Cancer Research Center, Ingalls Memorial Hospital, Harvey.
L J NastoupilDepartment of Lymphoma/Myeloma, University of Texas MD Anderson Cancer Center, Houston.
C R FlowersDivision of Hematology and Oncology, Winship Cancer Institute, Emory University-School of Medicine, Atlanta, USA.
AbbVie (United States) · USThe University of Texas MD Anderson Cancer Center · USAin Shams University · EGEmory University · USHenry Ford Hospital · USIngalls Memorial Hospital · USJohns Hopkins University · USUniversity of California, Los Angeles · USUniversity of California, San Diego · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Venetoclax is a selective, potent inhibitor of the anti-apoptotic B-cell leukemia/lymphoma-2 protein approved for treatment of chronic lymphocytic leukemia. We conducted a dose-finding study of venetoclax in combination with bendamustine-rituximab (BR) in patients with relapsed/refractory non-Hodgkin's lymphoma (NHL). Patients and methods: BR was given for six cycles at standard doses. Intermittent and continuous oral venetoclax administration was explored at 50-1200 mg daily doses. Co-primary objectives included safety, pharmacokinetics (PKs), maximum-tolerated dose (MTD), and recommended phase II dose (RP2D); secondary objective was preliminary efficacy. Results: Sixty patients were enrolled: 32 with follicular lymphoma, 22 with diffuse large B-cell lymphoma, and 6 with marginal zone lymphoma. Nausea (70%), neutropenia (68%), diarrhea (55%), and thrombocytopenia (52%) were the most frequent adverse events (AEs). Most common grade 3/4 AEs were neutropenia (60%) and lymphopenia (38%). Serious AEs were reported in 24 patients; the most frequent were febrile neutropenia and disease progression (8% each). Five patients died from either disease progression (n = 4) or respiratory failure (n = 1). MTD was not reached; RP2D for venetoclax-BR combination was established as 800 mg daily continuously. Venetoclax PK exposure with and without BR was comparable. For all patients, overall response rate was 65%. Median duration of overall response, overall survival, and progression-free survival was 38.3 months [95% confidence interval (CI) 10.4-NR], not yet reached, and 10.7 months (95% CI 4.3-21.0), respectively. Conclusions: This study established the safety profile of venetoclax in combination with BR, and results demonstrated tolerability and preliminary efficacy of the combination. Additional follow-up is needed to better determine the future role of BR plus venetoclax in the treatment of relapsed/refractory B-cell NHL. Trial registered: Clinicaltrials.gov, NCT01594229.

Indexed as

AdultAgedAged, 80 and overAntineoplastic Combined Chemotherapy ProtocolsBendamustine HydrochlorideBridged Bicyclo Compounds, HeterocyclicChemotherapy-Induced Febrile NeutropeniaDisease ProgressionDrug Administration ScheduleDrug Resistance, NeoplasmFemaleHumansLymphoma, Non-HodgkinMaleMaximum Tolerated DoseMiddle AgedBendamustine HydrochlorideBridged Bicyclo Compounds, HeterocyclicRituximabSulfonamidesvenetoclax

Identifiers

PMID30060083
PMCPMC6158762
OpenAlexW2883570202

What OpenQuestion holds

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LicenceCC BY-NC
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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.