Evidence map›Paper›PMID 39363864›Full record

Trial reportHaematologica2025

Pirtobrutinib monotherapy in Bruton tyrosine kinase inhibitor-intolerant patients with B-cell malignancies: results of the phase I/II BRUIN trial.

Nirav N Shah, Michael Wang, Lindsey E Roeker, Krish Patel, Jennifer A Woyach, William G Wierda, Chaitra S Ujjani, Toby A Eyre, Pier Luigi Zinzani, Alvaro J Alencar and 25 more

Abstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
In one paragraph

Trial report in Haematologica, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed, 1 pooled it
–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

17 citing papers in PubMed, 1 synthesis or guideline pooled it.

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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

35 authors.

Nirav N ShahMedical College of Wisconsin, Milwaukee, WI. nishah@mcw.edu.
Michael WangMD Anderson Cancer Center, Houston, TX.
Lindsey E RoekerMemorial Sloan Kettering Cancer Center, New York, NY.
Krish PatelSwedish Cancer Institute, Center for Blood Disorders and Cellular Therapy, Seattle, WA.
Jennifer A WoyachThe Ohio State University Comprehensive Cancer Center, Columbus, OH.
William G WierdaDepartment of Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX.
Chaitra S UjjaniUniversity of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA.
Toby A EyreOxford University Hospitals NHS Foundation Trust, Churchill Cancer Center, Oxford.
Pier Luigi ZinzaniInstitute of Hematology "Seragnoli" University of Bologna, Bologna.
Alvaro J AlencarUniversity of Miami Sylvester Comprehensive Cancer Center, Miami, FL.
Paolo GhiaUniversita Vita-Salute San Raffaele, Milano, Italy; IRCCS Ospedale San Raffaele, Milano.
Nicole LamannaNew York-Presbyterian Columbia University Medical Center, New York, NY.
Marc S HoffmannHematologic Malignancies and Cellular Therapeutics, University of Kansas Medical Center, Kansas City, KS.
Manish R PatelFlorida Cancer Specialists/Sarah Cannon Research Institute, Sarasota, FL.
Ian FlinnSarah Cannon Research Institute, Nashville, TN.
James N GersonLymphoma Program, Abramson Cancer Center, Philadelphia, PA.
Shuo MaRobert H. Lurie Comprehensive Cancer Center, Division of Hematology-Oncology, Northwestern University Feinberg School of Medicine, Chicago, IL.
Catherine C CoombsUniversity of California Irvine, Irvine, CA.
Chan Y CheahLinear Clinical Research and Sir Charles Gairdner Hospital, Perth.
Ewa Lech-MarandaInstitute of Hematology and Transfusion Medicine, Warsaw, Poland.
Bita FakhriDivision of Hematology at Stanford University School of Medicine, Stanford, CA.
Won Seog KimDivision of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul.
Minal A BarveMary Crowley Cancer Research Center, Dallas, TX.
Jonathon B CohenWinship Cancer Institute, Emory University, Atlanta, GA.
Wojciech JurczakMaria Sklodowska-Curie National Research Institute of Oncology, Krakow, Poland.
Talha MunirDepartment of Haematology, St. James's University Hospital, Leeds.
Meghan C ThompsonMemorial Sloan Kettering Cancer Center, New York, NY.
Donald E TsaiLoxo@Lilly, Indianapolis, IN.
Katherine BaoLoxo@Lilly, Indianapolis, IN.
Nicholas A CangemiLoxo@Lilly, Indianapolis, IN.
Jennifer F KheraniLoxo@Lilly, Indianapolis, IN.
Richard A WalgrenLoxo@Lilly, Indianapolis, IN.
Hongmei HanLoxo@Lilly, Indianapolis, IN.
Amy S RuppertEli Lilly and Company, Indianapolis, IN.
Jennifer R BrownChronic Lymphocytic Leukemia Center, Division of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA.

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
NCI NIH HHS P30 CA008748NCI NIH HHS P30 CA016672
6 · The paper itself

Abstract

Bruton tyrosine kinase inhibitors (BTKi) have transformed the treatment of B-cell malignancies, but intolerance has often led to their discontinuation. The phase I/II BRUIN study evaluated pirtobrutinib, a highly selective non-covalent (reversible) BTKi, in patients with relapsed / refractory B-cell malignancies (clinicaltrials.gov 03740529). Pirtobrutinib was investigated in 127 patients with intolerance to at least one prior BTKi therapy in the absence of progressive disease. The most common adverse event (AE) leading to BTKi discontinuation was cardiac disorders (N=40, 31.5%), specifically atrial fibrillation (N=30, 23.6%). The median follow-up was 17.4 months and the median time on pirtobrutinib was 15.3 months. The most common reasons for pirtobrutinib discontinuation were progressive disease (26.8%), AE (10.2%) or death (5.5%). The most frequent treatment-emergent AE were fatigue (39.4%) and neutropenia (37.0%). Among patients who discontinued a prior BTKi for a cardiac issue, 75% had no recurrence of their cardiac AE. No patient discontinued pirtobrutinib for the same AE that led to discontinuation of the prior BTKi. In 78 chronic lymphocytic / small lymphocytic lymphoma (CLL/SLL) and 21 mantle cell lymphoma (MCL) patients intolerant to prior BTKi, overall response rate to pirtobrutinib was 76.9% and 81.0%, respectively. Median progression-free survival for CLL/SLL was 28.4 months but was not estimable for MCL. These results suggest that pirtobrutinib was safe, well-tolerated, and an efficacious option in patients with prior BTKi-intolerance.

Indexed as

Agammaglobulinaemia Tyrosine KinaseProtein Kinase InhibitorsAdultAgedAged, 80 and overAntineoplastic AgentsDrug Resistance, NeoplasmFemaleHumansLeukemia, B-CellLymphoma, B-CellMaleMiddle AgedPyrimidinesTreatment OutcomeTyrosine Kinase InhibitorsAgammaglobulinaemia Tyrosine KinaseAntineoplastic AgentsBTK protein, humanProtein Kinase InhibitorsPyrimidinesTyrosine Kinase Inhibitors

Identifiers

PMID39363864
PMCPMC11694105

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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 Socratic graph.