Evidence map›Paper›PMID 39213466›Full record

SynthesisJournal of clinical oncology : official journal of the American Society of Clinical Oncology2025

End Point Surrogacy in First-Line Chronic Lymphocytic Leukemia.

Florian Simon, Rudy Ligtvoet, Sandra Robrecht, Paula Cramer, Nadine Kutsch, Moritz Fürstenau, Valentin Goede, Julia von Tresckow, Petra Langerbeins, Anna-Maria Fink and 23 more

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Measurable Residual Disease.Methods in molecular biology (Clifton, N.J.) · 2027
    Article
  2. Refined Continuous Risk Index for Accurately Predicting Outcomes of Patients With Chronic Lymphocytic Leukemia After Limited-Duration Therapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026
    Article
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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

33 authors.

Florian SimonFaculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany.ORCID 0000-0002-2700-3717
Rudy LigtvoetFaculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany.ORCID 0000-0001-6546-0911
Sandra RobrechtFaculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany.
Paula CramerFaculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany.ORCID 0000-0003-4046-9922
Nadine KutschFaculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany.ORCID 0000-0001-9559-8575
Moritz FürstenauFaculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany.ORCID 0000-0002-6593-0140
Valentin GoedeSt Marienhospital Cologne, Oncogeriatric Unit, Department of Geriatric Medicine, Cologne, Germany.
Julia von TresckowClinic for Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
Petra LangerbeinsFaculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany.ORCID 0000-0002-6654-0304
Anna-Maria FinkFaculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany.ORCID 0000-0002-7669-7890
Henriette HuberStädtisches Klinikum Karlsruhe, Karlsruhe, Germany.
Eugen TauschDepartment of Internal Medicine III, Division of CLL, Ulm University, Ulm, Germany.ORCID 0000-0002-9503-1226
Christof SchneiderDepartment of Internal Medicine III, Division of CLL, Ulm University, Ulm, Germany.
Clemens M WendtnerDepartment of Medicine III, University Hospital, LMU Munich, Munich, Germany.
Matthias RitgenDepartment II of Internal Medicine, University of Schleswig-Holstein, Kiel, Germany.
Martin DreylingDepartment of Medicine III, Ludwig-Maximilians-University Hospital, Munich, Germany.ORCID 0000-0002-0358-5249
Lothar MüllerStudy Centrum Unter Ems, Practice for Oncology and Hematology, Leer, Germany.ORCID 0000-0001-9252-4650
Lutz JacobaschPraxis of Haematology and Oncology, Dresden, Germany.
Werner J HeinzCaritas-Krankenhaus Bad Mergentheim, Medizinische Klinik II, Bad Mergentheim, Germany.ORCID 0000-0002-7833-9202
Ursula Vehling-KaiserOutpatient Clinic, Landshut, Germany.
Liliya SivchevaFirst Department of Internal Medicine, Multiprofile Hospital for Active Treatment - HristoBotev, Vratsa, Bulgaria.
Sebastian BöttcherDepartment of Medicine III Hematology, Oncology and Palliative Care, University Hospital, Rostock, Germany.ORCID 0000-0002-3603-761X
Peter DregerDepartment of Hematology, Oncology and Rheumatology, Heidelberg University Hospital, Heidelberg, Germany.ORCID 0000-0002-7429-8570
Thomas IllmerPraxis of Haematology and Oncology, Dresden, Germany.
Michael GregorDivision of Hematology, Cantonal Hospital of Lucerne, Lucerne, Switzerland.
Philipp B StaberDepartment of Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, Vienna, Austria.ORCID 0000-0001-6729-7708
Stephan StilgenbauerDepartment of Internal Medicine III, Division of CLL, Ulm University, Ulm, Germany.
Carsten U NiemannDepartment of Hematology, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.ORCID 0000-0001-9880-5242
Arnon P KaterAcademic Medical Department of Hematology, Cancer Center, Amsterdam, University of Amsterdam, Amsterdam, the Netherlands.ORCID 0000-0003-3190-1891
Kirsten FischerFaculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany.
Barbara EichhorstFaculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany.
Michael HallekFaculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany.ORCID 0000-0002-7425-4455
Othman Al-SawafFaculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf; German CLL Study Group, University of Cologne, Cologne, Germany.ORCID 0000-0001-9895-0570

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeSurrogate end points are commonly used to estimate treatment efficacy in clinical studies of chronic lymphocytic leukemia (CLL). This patient- and trial-level analysis describes the correlation between progression-free survival (PFS) and minimal residual disease (MRD) with overall survival (OS) in first-line trials for CLL. PATIENTS AND

methodsFirst, patient-level correlation was confirmed using source data from 12 frontline German CLL Study Group (GCLLSG)-trials. Additionally, a joint-frailty copula model was fitted to validate correlation in the setting of targeted therapies (TT). Second, a meta-analysis of first-line phase III trials in CLL from 2008 to 2024 was performed. Treatment effect correlation was quantified from seven GCLLSG and nine published trials, using hazard ratios (HRs) for time-to-event and odds ratios for binary end points.

resultsThe GCLLSG analysis set comprised 4,237 patients. Patient-level correlation for PFS/OS was strong with Spearman Rho >0.9. The joint-frailty copula indicated a weak correlation for chemotherapy/chemoimmunotherapy (C/CIT) with a tau of 0.52 (95% CI, 0.49 to 0.55) while the correlation was strong for TT (tau, 0.91 [95% CI, 0.89 to 0.93). The meta-analysis set contained a total of 8,065 patients including 5,198 (64%) patients treated with C/CIT and 2,867 (36%) treated with TT. Treatment-effect correlation of the HRs for PFS and OS was

conclusionPatient-level correlation was confirmed in the setting of TTs while treatment-effect correlation between PFS and OS remains uncertain. MRD response status showed a high treatment-effect correlation with PFS but not OS, with the caveat of a limited number of randomized trials with available MRD data.

Indexed as

Leukemia, Lymphocytic, Chronic, B-CellClinical Trials, Phase III as TopicFemaleHumansMaleNeoplasm, ResidualProgression-Free Survival

Identifiers

PMID39213466
PMCPMC11771364

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