Unit of Hematology, Azienda Ospedaliera Universitaria Senese and University of Siena, Siena, Italy.
Hematology Department, Careggi Hospital and University of Florence, Florence, Italy.
Ann Hematol. 2023 Apr;102(4):841-849. doi: 10.1007/s00277-023-05113-9. Epub 2023 Feb 3.
Ibrutinib represents the first approved treatment for patients with Waldenström macroglobulinemia (WM). There are very few published experiences outside of a clinical trial. In this study, we investigated treatment response, survival, and safety in a real life setting. We retrospectively analyzed 49 consecutive R/R WM patients, managed in 8 Tuscan onco-hematological centers, that received ibrutinib after its approval, at a maximum dose of 420 mg once per day, until disease progression or unacceptable toxicity. Median age was 65 years (range 32-86), and the median number of previous regimens was 2 (range 1-5). Overall and major response rate were 91.8% and 87.7%, respectively. At best response, median IgM level declined from 3,094 to 831 mg/dl, and Hb level increased from 10.4 to 12.7 g/dl. In an intention-to-treat analysis, 36/49 patients (73.5%) were still receiving treatment, while 13/49 (26.5%) had discontinued therapy. Six out of 49 cases (12.2%) relapsed after an initial response, and 13/49 (26.5%) had a dose reduction. Estimated 2-year PFS, DOR, and OS were 76.7%, 88.7%, and 84.1%, respectively. After a median follow-up of 18.3 months, 43/49 patients (87.8%) were alive. The most frequent AE included atrial fibrillation or flutter (6/49 cases, 12.2%), bleeding (6/49 cases, 12.2%), arthralgia/myalgia (5/49 cases, 10.2%). Ibrutinib is a suitable treatment option for R/R WM patients and also suggested by ESMO, NCCN, and other societies. PFS and OS were durable, and DOR was sustained for responsive patients. Treatment toxicity is not negligible, but manageable in most cases without treatment discontinuation.
伊布替尼是首个获批用于治疗华氏巨球蛋白血症（WM）的药物。除了临床试验，相关经验非常有限。本研究旨在评估真实世界中伊布替尼的治疗应答、生存和安全性。我们回顾性分析了 49 例在获得伊布替尼批准后，于 8 家托斯卡纳肿瘤血液中心接受治疗的复发/难治性 WM 患者。患者接受最大剂量 420mg 伊布替尼，每日一次，直至疾病进展或不可耐受毒性。中位年龄为 65 岁（32-86 岁），中位治疗线数为 2 线（1-5 线）。总体反应率和主要反应率分别为 91.8%和 87.7%。最佳反应时，中位 IgM 水平从 3094mg/dl 下降至 831mg/dl，Hb 水平从 10.4g/dl 升高至 12.7g/dl。意向性治疗分析中，49 例患者中有 36 例（73.5%）仍在接受治疗，13 例（26.5%）已停药。6 例患者在获得初始缓解后复发（12.2%），13 例患者（26.5%）需要降低剂量。估计 2 年 PFS、DOR 和 OS 分别为 76.7%、88.7%和 84.1%。中位随访 18.3 个月时，49 例患者中有 43 例（87.8%）存活。最常见的 AE 包括心房颤动或扑动（6 例，12.2%）、出血（6 例，12.2%）、关节痛/肌痛（5 例，10.2%）。伊布替尼是复发/难治性 WM 患者的一种合适的治疗选择，也被 ESMO、NCCN 和其他学会推荐。PFS 和 OS 持久，对有应答的患者，DOR 持续。治疗毒性不可忽视，但在大多数情况下，无需停药即可控制。
