a Department of Hematology , Jagiellonian University , Kraków , Poland.
b Department of Lymphoma and Myeloma , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
Expert Rev Clin Pharmacol. 2019 Mar;12(3):179-187. doi: 10.1080/17512433.2019.1568868. Epub 2019 Jan 26.
Although advances in mantle cell lymphoma (MCL) therapy have improved overall survival (OS), managing relapsed/refractory (R/R) cases remains a great challenge. Bruton tyrosine kinase (BTK) inhibitors have broadened therapeutic options in MCL and became the backbone of second-line strategies. Areas covered: Ibrutinib, the first-in-class BTK inhibitor registered for MCL therapy, is efficient, with clear benefits of its use. However, ibrutinib-related adverse events due to off-target inhibition of other kinases led to the development of more selective molecules with comparable efficacy and better safety profiles. Expert commentary: Acalabrutinib, a new BTK inhibitor, currently being evaluated in numerous clinical studies is approved by FDA in relapsing/refractory MCL. Its role will evolve over the next few years. Efficacy and good tolerability of acalabrutinib gives even greater opportunity for potential upfront use and new therapeutic combinations, including monoclonal antibodies, antibody-drug conjugates, immune checkpoint inhibitors, bcl-2 (B-cell lymphoma-2) or IP3K (phosphoinositide 3-kinase) inhibitors.
虽然套细胞淋巴瘤（MCL）治疗的进展提高了总生存率（OS），但管理复发/难治性（R/R）病例仍然是一个巨大的挑战。布鲁顿酪氨酸激酶（BTK）抑制剂拓宽了 MCL 的治疗选择，并成为二线策略的基础。
伊布替尼，首个用于 MCL 治疗的 BTK 抑制剂，具有疗效，其使用具有明显的益处。然而，由于对其他激酶的非靶向抑制，伊布替尼相关的不良反应导致了具有可比疗效和更好安全性的更具选择性的分子的发展。
阿卡替尼，一种新的 BTK 抑制剂，目前正在多项临床研究中进行评估，已被 FDA 批准用于复发/难治性 MCL。在未来几年，它的作用将不断发展。阿卡替尼的疗效和良好的耐受性为其潜在的一线应用和新的治疗组合提供了更大的机会，包括单克隆抗体、抗体药物偶联物、免疫检查点抑制剂、bcl-2（B 细胞淋巴瘤-2）或 IP3K（磷酸肌醇 3-激酶）抑制剂。
