Pirtobrutinib monotherapy in Bruton tyrosine kinase inhibitor-intolerant patients with B-cell malignancies: Results of the phase I/II BRUIN trial Journal Article
| Authors: | Shah, N. N.; Wang, M.; Roeker, L. E.; Patel, K.; Woyach, J. A.; Wierda, W. G.; Ujjani, C. S.; Eyre, T. A.; Zinzani, P. L.; Alencar, A. J.; Ghia, P.; Lamanna, N.; Hoffmann, M. S.; Patel, M. R.; Flinn, I.; Gerson, J. N.; Ma, S.; Coombs, C. C.; Cheah, C. Y.; Lech-Maranda, E.; Fakhri, B.; Kim, W. S.; Barve, M. A.; Cohen, J. B.; Jurczak, W.; Munir, T.; Thompson, M. C.; Tsai, D. E.; Bao, K.; Cangemi, N. A.; Kherani, J. F.; Walgren, R. A.; Han, H.; Ruppert, A. S.; Brown, J. R. |
| Article Title: | Pirtobrutinib monotherapy in Bruton tyrosine kinase inhibitor-intolerant patients with B-cell malignancies: Results of the phase I/II BRUIN trial |
| 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. © 2025 Ferrata Storti Foundation. |
| Keywords: | adult; treatment outcome; aged; aged, 80 and over; middle aged; overall survival; clinical trial; fatigue; mortality; drug efficacy; drug safety; hypertension; monotherapy; antineoplastic agents; rituximab; antineoplastic agent; progression free survival; mantle cell lymphoma; neutrophil count; phase 2 clinical trial; protein kinase inhibitor; patient monitoring; drug resistance; drug resistance, neoplasm; protein tyrosine kinase; pyrimidines; tyrosine kinase inhibitors; protein tyrosine kinase inhibitor; protein kinase inhibitors; b cell lymphoma; lymphoma, b-cell; heart failure; multicenter study; splenomegaly; warfarin; sepsis; chimeric antigen receptor; stomach cancer; merkel cell carcinoma; rheumatoid arthritis; phase 1 clinical trial; heart arrhythmia; drug therapy; pyrimidine derivative; hematoma; atrial fibrillation; tachycardia; platelet count; non-hodgkin lymphoma; ecchymosis; drug industry; b cell leukemia; non small cell lung cancer; petechia; lymphocytosis; bruton tyrosine kinase; leukemia, b-cell; ibrutinib; very elderly; humans; human; male; female; article; agammaglobulinaemia tyrosine kinase; obinutuzumab; venetoclax; zanubrutinib; pirtobrutinib; btk protein, human; trillium |
| Journal Title: | Haematologica |
| Volume: | 110 |
| Issue: | 1 |
| ISSN: | 0390-6078 |
| Publisher: | Ferrata Storti Foundation |
| Date Published: | 2025-01-01 |
| Start Page: | 92 |
| End Page: | 102 |
| Language: | English |
| DOI: | 10.3324/haematol.2024.285754 |
| PUBMED: | 39363864 |
| PROVIDER: | scopus |
| PMCID: | PMC11694105 |
| DOI/URL: | |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- Source: Scopus |
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