Division of Hematology, Department of Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Eur J Haematol. 2020 Jun;104(6):588-593. doi: 10.1111/ejh.13401. Epub 2020 Mar 15.
Hemolysis is a sporadically reported but potentially serious side effect of the proteasome inhibitor carfilzomib. We aimed to investigate the frequency of hemolysis in an unselected cohort.
We performed a retrospective, single-center study of the incidence of hemolysis in patients treated with carfilzomib, based mainly on consecutive haptoglobin levels. The patients were diagnosed with myeloma (n = 20), AL amyloidosis (n = 3), and light-chain deposition disease (n = 1). Carfilzomib treatment was applied after a median of 3 (range: 1-7) therapy lines.
Haptoglobin levels were normal/increased before, generally suppressed during, and normalized after treatment with carfilzomib. Very low haptoglobin (<0.1 g/L) implying the presence of hemolysis was observed in 16 of 24 (67%) patients during carfilzomib therapy. Hemolysis was mild in 11 of 16 (69%) affected patients, whereas 5 of 16 (31%) required transfusion. Severe hemolysis was explained by thrombotic microangiopathy (TMA) in one patient who died of the complication. Mechanisms were unclear in the remaining 15 patients.
Hemolysis was surprisingly common but mostly mild during carfilzomib treatment. However, the possibility of TMA should be kept in mind in this setting. Hypothetically, non-TMA hemolysis could be attributed to the accumulation of globin chains due to the suppression of eukaryotic translation initiation inhibition by carfilzomib.
溶血性贫血是蛋白酶体抑制剂卡非佐米偶尔报道但潜在严重的副作用。我们旨在调查未选择队列中溶血性贫血的频率。
我们对接受卡非佐米治疗的患者进行了回顾性、单中心研究,主要基于连续的结合珠蛋白水平来确定溶血性贫血的发生率。患者被诊断为多发性骨髓瘤(n=20)、AL 淀粉样变性(n=3)和轻链沉积病(n=1)。卡非佐米治疗在中位数 3 次(范围:1-7 次)治疗线后应用。
在接受卡非佐米治疗前,结合珠蛋白水平正常/升高,通常在治疗期间受到抑制,治疗后恢复正常。在 24 名患者中,有 16 名(67%)在卡非佐米治疗期间观察到非常低的结合珠蛋白(<0.1g/L),提示存在溶血性贫血。在 16 名受影响的患者中,11 名(69%)溶血性贫血为轻度,5 名(31%)需要输血。一名死于并发症的患者的严重溶血性贫血由血栓性微血管病(TMA)引起。在其余 15 名患者中,机制尚不清楚。
在接受卡非佐米治疗期间,溶血性贫血非常常见,但大多为轻度。然而,在这种情况下应注意 TMA 的可能性。假设,非 TMA 溶血性贫血可能归因于卡非佐米抑制真核翻译起始抑制导致的球蛋白链堆积。