Department of Hematology and Oncology, University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
J Cancer Res Clin Oncol. 2018 Aug;144(8):1531-1538. doi: 10.1007/s00432-018-2665-x. Epub 2018 May 14.
Iron overload (IOL) due to repetitive transfusions of packed red blood cells (pRBC) has a major impact on morbidity and mortality in patients with inherited bone marrow failure syndromes and hemoglobinopathies such as thalassemia and sickle cell disease. However, whether IOL influences the outcome of elderly patients with myeloid malignancies is not yet clear. Moreover, clinical trials have reported high drop-out rates during treatment with the oral iron chelator deferasirox (DFX).
Here we report the results of a 2-year prospective observational study that aimed at describing the routine use of DFX in patients with hematological malignancies with regard to safety, efficacy and handling of the drug in a routine setting.
A total of 406 patients were included. 58% of the patients were male. Most of the patients had myelodysplastic syndromes (MDS) (68%) and myeloproliferative neoplasms (MPN) (14%). Median time from first transfusion to study enrollment was 1.1 years (0-25.5 years) and most patients were chelation naive (91%) at enrollment. With regard to transfusion burden, most of the patients were moderately or mildly transfusion-dependent with 53% receiving 2-4 and 27% receiving less than 2 units of pRBC per month. Serum ferritin decreased from a mean of 2305 μg/l (± 1449 μg/l) to a mean of 1910 μg/l (± 1529 μg/l) at 24 months. There was no substantial change in transfusion-dependence during the observation period. Dose adjustments were reported in 48% of the patients with dose-escalation strategies being the most frequent reason for dosage increases (49%). The median observation time was 355 days (5-1080 days). Median duration of exposure to DFX was 322 days (2-1078 days). Two-hundred and ninety (72%) patients discontinued the trial prematurely after a median time of 235 days (1-808 days). Death (29%) and adverse events (23%) were the main reasons for discontinuation. Eleven percent of the patients discontinued treatment due to sufficient decrease in serum ferritin. Most frequent adverse events were decrease in creatinine clearance (22%), increase in serum creatinine (18%) and diarrhea (16%).
This descriptive trial confirms the efficacy of DFX in decreasing the serum ferritin. Moreover, the high drop-out rates seen in prospective trials are recapitulated in this study, which can be attributed to adverse events in a substantial proportion of patients.
由于反复输注浓缩红细胞（pRBC），铁过载（IOL）对遗传性骨髓衰竭综合征和血红蛋白病患者（如地中海贫血和镰状细胞病）的发病率和死亡率有重大影响。然而，IOL 是否会影响老年骨髓恶性肿瘤患者的预后尚不清楚。此外，临床试验报告称，口服铁螯合剂地拉罗司（DFX）治疗期间的脱落率很高。
本研究报告了一项为期 2 年的前瞻性观察性研究结果，该研究旨在描述 DFX 在血液系统恶性肿瘤患者中的常规使用情况，包括安全性、疗效和常规用药情况。
共纳入 406 例患者。58%的患者为男性。大多数患者患有骨髓增生异常综合征（MDS）（68%）和骨髓增殖性肿瘤（MPN）（14%）。从首次输血到研究入组的中位时间为 1.1 年（0-25.5 年），大多数患者在入组时为首次螯合治疗（91%）。在输血负担方面，大多数患者为中度或轻度输血依赖性，53%的患者每月接受 2-4 单位 pRBC，27%的患者每月接受少于 2 单位 pRBC。血清铁蛋白从入组时的 2305μg/l（±1449μg/l）降至 24 个月时的 1910μg/l（±1529μg/l）。在观察期间，输血依赖性没有实质性变化。48%的患者报告了剂量调整，其中增加剂量的策略是最常见的原因（49%）。中位观察时间为 355 天（5-1080 天）。中位 DFX 暴露时间为 322 天（2-1078 天）。290 例（72%）患者在中位时间 235 天（1-808 天）后提前退出试验。死亡（29%）和不良事件（23%）是提前退出试验的主要原因。由于血清铁蛋白明显下降，11%的患者停止了治疗。最常见的不良事件是肌酐清除率下降（22%）、血清肌酐升高（18%）和腹泻（16%）。
本描述性试验证实了 DFX 降低血清铁蛋白的疗效。此外，前瞻性试验中观察到的高脱落率在本研究中得到了重现，这可能归因于相当一部分患者的不良事件。
