Zaidi Uzma, Kaleem Bushra, Borhany Munira, Maqsood Sidra, Fatima Naveena, Sufaida Gul, Ansari Saqib Hussain, Farzana Tasneem, Shamsi Tahir Sultan
Department of Clinical Hematology, National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, Pakistan,
Department of Clinical Research, National Institute of Blood Diseases & Bone Marrow Transplantation, Karachi, Pakistan.
Cancer Manag Res. 2019 Feb 15;11:1493-1502. doi: 10.2147/CMAR.S181911. eCollection 2019.
Nilotinib (Tasigna®) is a second-generation tyrosine kinase inhibitor that shows faster and deeper molecular responses (MR) in comparison to Imatinib as initial therapy in chronic phase chronic myeloid leukemia (CML). Efficacy and safety data for nilotinib in the Asian population is scarce, particularly in Pakistan. We aimed to determine the MR to nilotinib and its safety profile in patients with chronic phase CML.
This observational study was conducted among 173 patients with newly diagnosed CML presenting in the chronic phase. Most patients (50.1%) had a high Sokal score at diagnosis. All patients received nilotinib 600 mg/day. The hematological and molecular responses were assessed at 3 and 6 months respectively and thereafter at 6-monthly intervals. Long-term event free survival (EFS), transformation free survival (TFS), overall survival (OS) and adverse events were observed.
Cumulative incidence of major MR (MMR) was 86% and deep MR (DMR ie MR 4.0 and MR4.5) was 39%. Early MMR and DMR after 6 months of therapy were achieved by 74.9% and 37% of patients, respectively. Two-year EFS, TFS and OS rates for all patients were 91.9%, 92% and 92.3%, respectively. At median follow-up of 24 months, 81% and 49% of patients sustained MMR and DMR, respectively. The main adverse events were weight gain (4.6%) and abdominal pain (4%).
This study showed promising results in terms of achievement of early and sustained DMR in chronic phase CML, therefore, we recommend nilotinib as frontline treatment in Pakistani population.
尼罗替尼（达希纳®）是一种第二代酪氨酸激酶抑制剂，与伊马替尼相比，作为慢性期慢性髓性白血病（CML）的初始治疗药物，它能显示出更快、更深的分子反应（MR）。尼罗替尼在亚洲人群中的疗效和安全性数据稀缺，尤其是在巴基斯坦。我们旨在确定慢性期CML患者对尼罗替尼的分子反应及其安全性。
本观察性研究纳入了173例新诊断为慢性期CML的患者。大多数患者（50.1%）在诊断时Sokal评分较高。所有患者均接受每日600毫克尼罗替尼治疗。分别在3个月和6个月时评估血液学和分子反应，此后每6个月评估一次。观察长期无事件生存（EFS）、无转化生存（TFS）、总生存（OS）和不良事件。
主要分子反应（MMR）的累积发生率为86%，深度分子反应（DMR，即MR 4.0和MR4.5）为39%。治疗6个月后，分别有74.9%和37%的患者实现了早期MMR和DMR。所有患者的两年EFS、TFS和OS率分别为91.9%、92%和92.3%。在24个月的中位随访期，分别有81%和49%的患者维持MMR和DMR。主要不良事件为体重增加（4.6%）和腹痛（4%）。
本研究显示在慢性期CML实现早期和持续DMR方面取得了有前景的结果，因此，我们推荐尼罗替尼作为巴基斯坦人群的一线治疗药物。
