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

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.

Authors

Institutions

Publication Details

Journal
Haematologica
Published
2024-10-03
DOI
https://doi.org/10.3324/haematol.2024.285754
Citations
11
Primary Topic
Chronic Lymphocytic Leukemia Research
Type
article
Field-Weighted Citation Impact
4.82

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

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

Ian W. Flinn, Manish R. Patel, Marc Hoffmann, Jonathon Brett Cohen et al.
11 citations
Haematologica
Chronic Lymphocytic Leukemia Research
4.82
article

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

Ian W. Flinn, Manish R. Patel, Marc Hoffmann, Jonathon Brett Cohen, Richard A. Walgren, Nicole Lamanna, Jennifer Ann Woyach, Minal Barve, Jennifer R. Brown, Catherine C. Coombs, Talha Munir, Ewa Lech‐Marańda, Donald E. Tsai, Krish Patel, James N. Gerson, Lindsey E. Roeker, Katherine Bao, Hong‐Mei Han, Nicholas A. Cangemi, Toby A. Eyre, Meghan C. Thompson, Chan Yoon Cheah, Jennifer Kherani, Michael Wang, Chaitra S. Ujjani, Shuo Ma, Bita Fakhri, Alvaro Jose Alencar, Paolo Ghia, Nirav Niranjan Shah, William G. Wierda, Wojciech J. Jurczak, Pier Luigi Zinzani, Amy S. Ruppert, Won Seog Kim
article en
11 citations

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.

HaematologicaVol. 110(1)
Memorial Sloan Kettering Cancer Center (US), The University of Texas MD Anderson Cancer Center (US), University of Miami (US), Emory University (US), Eli Lilly (United States) (US), University of Washington (US), University of California, Irvine (US), Medical College of Wisconsin (US), Columbia University Irving Medical Center (US), Churchill Hospital (GB), St James's University Hospital (GB), Samsung Medical Center (KR), Sir Charles Gairdner Hospital (AU), Mary Crowley Cancer Research Center (US), Fred Hutch Cancer Center (US), Instytut Hematologii i Transfuzjologi (PL), Swedish Medical Center (US), Sarah Cannon (US), Center for Cancer and Blood Disorders (US), Dana-Farber Cancer Institute (US), University of Kansas Medical Center (US), Loxo Oncology at Lilly (United States) (US), IRCCS Ospedale San Raffaele (IT), Stanford Medicine (US), Istituto Oncologico Romagnolo (IT), Oxford University Hospitals NHS Trust (GB), The Maria Sklodowska-Curie National Research Institute of Oncology (PL), Sylvester Comprehensive Cancer Center (US), Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Abramson Cancer Center (US), The Ohio State University (US), Sungkyunkwan University (KR), University of Bologna (IT), Stanford University (US)
Abbott Laboratories, Amgen, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, AstraZeneca, Sanofi, Leukemia and Lymphoma Society, Gilead Sciences, CLL Global Research Foundation, American Society of Clinical Oncology, Celgene, Massachusetts Medical Society, TG Therapeutics, National Comprehensive Cancer Network, LAM Therapeutics, Atara Biotherapeutics, MEI Pharma, Agios Pharmaceuticals, Constellation Pharmaceuticals, bluebird bio, Adaptive Biotechnologies, Unum Therapeutics, BeiGene, Incyte, City of Hope, Celltrion, Galápagos, Seagen, Servier, Swedish Orphan Biovitrum, MorphoSys, Grifols, Aptitude Health, National Institutes of Health, Genentech, Takeda Oncology, Kite Pharma, Pharmacyclics, Juno Therapeutics, Loxo Oncology, National Cancer Institute, Janssen Biotech, Cilag
Good health and well-being
Openalex Percentile: Top 4%
Chronic Lymphocytic Leukemia Research
4.82
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.