Evidence map›Paper›PMID 38500476›Full record

ArticleBritish journal of haematology2024

Safety and efficacy of zandelisib plus zanubrutinib in previously treated follicular and mantle cell lymphomas.

Jacob D Soumerai, Catherine S Diefenbach, Deepa Jagadeesh, Adam Asch, Abhijeet Kumar, Michaela L Tsai, Thomas A Jandl, Izidore S Lossos, Vaishalee P Kenkre, Farrukh Awan and 6 more

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

Article in British journal of haematology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02914938 (A Three-Arm Study of ME-401 Monotherapy in Subjects With Relapsed/Refractory CLL, SLL, or FL, of ME-401 in Combination With Rituximab in Subjects With Relapsed/Refractory CLL/SLL or B-cell NHL, and of ME-401 in Combination With Zanubrutinib in Subjects With Relapsed/Refractory CLL/SLL or B-cell NHL), which is not on this map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
1.8field-weighted citation impact, top 16% 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.

NCT02914938 phase1terminatednot on this map

A Three-Arm Study of ME-401 Monotherapy in Subjects With Relapsed/Refractory CLL, SLL, or FL, of ME-401 in Combination With Rituximab in Subjects With Relapsed/Refractory CLL/SLL or B-cell NHL, and of ME-401 in Combination With Zanubrutinib in Subjects With Relapsed/Refractory CLL/SLL or B-cell NHL

TypeinterventionalSponsorMEI Pharma, Inc.Ran2016 to 2023Enrolled97ConditionsChronic Lymphocytic Leukemia (CLL), Small Lymphocytic Lymphoma (SLL), Follicular Lymphoma (FL), Marginal Zone B Cell LymphomaArmsME-401, Rituximab, Zanubrutinib
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. 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

16 authors at 14 institutions in 2 countries.

Jacob D SoumeraiMassachusetts General Hospital Cancer Center, Boston, Massachusetts, USA.ORCID https://orcid.org/0000-0002-3062-6819
Catherine S DiefenbachPerlmutter Cancer Center at NYU Langone Health, New York, New York, USA.ORCID https://orcid.org/0000-0003-1116-3246
Deepa JagadeeshDepartment of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, Ohio, USA.
Adam AschStephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
Abhijeet KumarUniversity of Arizona, Tucson, Arizona, USA.
Michaela L TsaiSwedish Cancer Institute, Seattle, Washington, USA.
Thomas A JandlStony Brook University Hospital, Stony Brook, New York, USA.
Izidore S LossosSylvester Comprehensive Cancer Center, University of Miami School of Medicine, Miami, Florida, USA.ORCID https://orcid.org/0000-0002-9346-9013
Vaishalee P KenkreCarbone Cancer Center, University of Wisconsin, Madison, Wisconsin, USA.
Farrukh AwanUniversity of Texas Southwestern Medical Center, Dallas, Texas, USA.ORCID https://orcid.org/0000-0003-1813-9812
William NovotnyBeiGene, LTD, Cambridge, Massachusetts, USA.
Jane HuangBeiGene, LTD, Cambridge, Massachusetts, USA.
Lu MiaoMEI Pharma, Inc., San Diego, California, USA.
Prabhu RajagopalanPR Consulting, Mountain Lakes, New Jersey, USA.
Richard G GhalieMEI Pharma, Inc., San Diego, California, USA.
Andrew D ZelenetzMemorial Sloan Kettering Cancer Center, New York, New York, USA.
Biogen (United States) · USMEI Pharma (United States) · USCleveland Clinic · USMassachusetts General Hospital · USMemorial Sloan Kettering Cancer Center · USMountain Lakes High School · USNYU Langone Health · USStony Brook University Hospital · USSwedish Medical Center · USThe University of Texas Southwestern Medical Center · USUniversity of Arizona · USUniversity of Miami · USUniversity of Oklahoma Health Sciences Center · USUniversity of Wisconsin–Madison · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Translating Stress Response Targeted Therapy for B-Cell LymphomasP50CA192937 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI DALLA-FAVERA, RICCARDO, ZELENETZ, ANDREW D. · 2016 to 2020
$10.9M
Predictive markers for personalized therapy in chronic lymphocytic leukemiaK08CA270202 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Jacob Soumerai · 2023 to 2026
$1.1M
Lymphoma Research FoundationNCI NIH HHS K08 CA270202NCI NIH HHS K08CA270202-01NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA192937
6 · The paper itself

Abstract

The combination of the phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor zandelisib with the Bruton's tyrosine kinase (BTK) inhibitor zanubrutinib was hypothesized to be synergistic and prevent resistance to single-agent therapy. This phase 1 study (NCT02914938) included a dose-finding stage in patients with relapsed/refractory (R/R) B-cell malignancies (n = 20) and disease-specific expansion cohorts in follicular lymphoma (FL; n = 31) or mantle cell lymphoma (MCL; n = 19). The recommended phase 2 dose was zandelisib 60 mg on Days 1-7 plus zanubrutinib 80 mg twice daily continuously in 28-day cycle. In the total population, the most common adverse events (AEs; all grades/grade 3-4) were neutropenia (35%/24%), diarrhoea (33%/2%), thrombocytopenia (32%/8%), anaemia (27%/8%), increased creatinine (25%/0%), contusion (21%/0%), fatigue (21%/2%), nausea (21%/2%) and increased aspartate aminotransferase (24%/6%). Three patients discontinued due to AEs. The overall response rate was 87% (complete response [CR] = 33%) for FL and 74% (CR = 47%) for MCL. The median duration of response and progression-free survival (PFS) were not reached in either group. The estimated 1-year PFS was 72.3% (95% confidence interval [CI], 51.9-85.1) for FL and 56.3% (95% CI, 28.9-76.7) for MCL (median follow-up: 16.5 and 10.9 months respectively). Zandelisib plus zanubrutinib was associated with high response rates and no increased toxicity compared to either agent alone.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsLymphoma, FollicularLymphoma, Mantle-CellPyrazolesPyrimidinesAdultAgammaglobulinaemia Tyrosine KinaseAgedAged, 80 and overFemaleHumansMaleMiddle AgedPiperidinesThiazolesTreatment OutcomeAgammaglobulinaemia Tyrosine KinasePiperidinesPyrazolesPyrimidinesThiazoleszanubrutinibclinical trialfollicular lymphomamantle cell lymphomazandelisibzanubrutinib

Identifiers

PMID38500476
PMCPMC11156518
OpenAlexW4392970713

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.