Shah Nirav N, Wang Michael, Roeker Lindsey E, Patel Krish, Woyach Jennifer A, Wierda William G, Ujjani Chaitra S, Eyre Toby A, Zinzani Pier Luigi, Alencar Alvaro J, Ghia Paolo, Lamanna Nicole, Hoffmann Marc S, Patel Manish R, Flinn Ian, Gerson James N, Ma Shuo, Coombs Catherine C, Cheah Chan Y, Lech-Maranda Ewa, Fakhri Bita, Kim Won Seog, Barve Minal A, Cohen Jonathon B, Jurczak Wojciech, Munir Talha, Thompson Meghan C, Tsai Donald E, Bao Katherine, Cangemi Nicholas A, Kherani Jennifer F, Walgren Richard A, Han Hongmei, Ruppert Amy S, Brown Jennifer R
Medical College of Wisconsin, Milwaukee, WI.
MD Anderson Cancer Center, Houston, TX.
Haematologica. 2025 Jan 1;110(1):92-102. doi: 10.3324/haematol.2024.285754.
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.
布鲁顿酪氨酸激酶抑制剂（BTKi）已经改变了B细胞恶性肿瘤的治疗方式，但不耐受情况常常导致其停用。I/II期BRUIN研究评估了pirtobrutinib（一种高度选择性的非共价（可逆）BTKi）在复发/难治性B细胞恶性肿瘤患者中的疗效（clinicaltrials.gov 03740529）。在127例对至少一种先前BTKi治疗不耐受且无疾病进展的患者中对pirtobrutinib进行了研究。导致BTKi停用的最常见不良事件（AE）是心脏疾病（N=40，31.5%），具体为心房颤动（N=30，23.6%）。中位随访时间为17.4个月，使用pirtobrutinib的中位时间为15.3个月。pirtobrutinib停用的最常见原因是疾病进展（26.8%）、AE（10.2%）或死亡（5.5%）。最常见的治疗中出现的AE是疲劳（39.4%）和中性粒细胞减少（37.0%）。在因心脏问题停用先前BTKi的患者中，75%的患者心脏AE未复发。没有患者因导致先前BTKi停用的相同AE而停用pirtobrutinib。在78例对先前BTKi不耐受的慢性淋巴细胞/小淋巴细胞淋巴瘤（CLL/SLL）患者和21例套细胞淋巴瘤（MCL）患者中，pirtobrutinib的总体缓解率分别为76.9%和81.0%。CLL/SLL的中位无进展生存期为28.4个月，但MCL的中位无进展生存期无法评估。这些结果表明，pirtobrutinib在先前对BTKi不耐受的患者中是安全、耐受性良好且有效的选择。
