Gryc Thomas, Putz Florian, Goerig Nicole, Ziegler Sonia, Fietkau Rainer, Distel Luitpold V, Schuster Barbara
Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Universitätsstraße 27, D-91054, Erlangen, Germany.
Radiat Oncol. 2017 Jun 28;12(1):109. doi: 10.1186/s13014-017-0827-7.
Idelalisib is approved for the treatment of relapsed chronic lymphocytic leukemia together with Rituximab and for monotherapy of follicular B-cell non-Hodgkin's lymphoma and small lymphocytic lymphoma. It is a potent and selective phosphatidylinositol 3-kinase-δ (PI3K-δ) inhibitor. PI3K-δ primarily is expressed in B-cells and prevents effectively proliferation in malignant B-cells.
We provide a detailed report on treatment history and photo documentation of acute adverse effects of radiation therapy with simultaneous Idelalisib medication in one case of B-CLL. Radiosensitivity tests were performed for the index patient under Idelalisib and after the addition of Idelalisib to healthy individuals' blood. Radiosensitivity in human lymphocytes was analyzed with a three color in situ hybridization assay. Primary skin fibroblasts were studied after a treatment with Idelalisib for apoptosis, necrosis and cell cycle using flow cytometry. DNA double-strand break repair was analyzed by γH2AX immunostaining.
The index patient presented a strong grade 2 radiodermatitis and grade 3 mucositis after irradiation with 20 Gy and a simultaneous intake of Idelalisib. Irradiations without Idelalisib medication were well tolerated and resulted in not more than grade 1 radiodermatitis. The index patient under Idelalisib had a radiosensitivity of 0.62 B/M which is in the range of clearly radiosensitive patients. A combined treatment of lymphocytes with 2 Gy and 10 nmol/l Idelalisib showed a tendency to an increased radiosensitivity. We found a clear increase of apoptosis as a result of the combined treatment in the Idelalisib dose range of 1 to 100 nmol/l compared to solely irradiated cells or solely Idelalisib treated cells (p = 0.05).
A combined Idelalisib radiotherapy treatment has an increased risk of side effects. However, combined therapy seems to be feasible when patients are monitored closely.
idelalisib被批准与利妥昔单抗联合用于治疗复发的慢性淋巴细胞白血病，以及用于滤泡性B细胞非霍奇金淋巴瘤和小淋巴细胞淋巴瘤的单药治疗。它是一种强效且选择性的磷脂酰肌醇3-激酶-δ（PI3K-δ）抑制剂。PI3K-δ主要在B细胞中表达，并有效阻止恶性B细胞的增殖。
我们提供了一份详细报告，内容涉及一例B细胞慢性淋巴细胞白血病患者在接受放射治疗并同时服用idelalisib时的治疗史及急性不良反应的照片记录。对该索引患者在服用idelalisib期间以及在健康个体血液中添加idelalisib后进行了放射敏感性测试。采用三色原位杂交分析法分析人淋巴细胞的放射敏感性。使用流式细胞术研究了idelalisib处理后的原代表皮成纤维细胞的凋亡、坏死和细胞周期情况。通过γH2AX免疫染色分析DNA双链断裂修复情况。
该索引患者在接受20 Gy照射并同时服用idelalisib后出现了严重的2级放射性皮炎和3级粘膜炎。未服用idelalisib进行照射时耐受性良好，放射性皮炎不超过1级。服用idelalisib的索引患者的放射敏感性为0.62 B/M，处于明显放射敏感患者的范围内。淋巴细胞联合2 Gy和10 nmol/l idelalisib治疗显示出放射敏感性增加的趋势。我们发现，与单纯照射细胞或单纯idelalisib处理的细胞相比，在1至100 nmol/l的idelalisib剂量范围内联合治疗导致凋亡明显增加（p = 0.05）。
idelalisib与放射治疗联合使用会增加副作用风险。然而，当对患者进行密切监测时，联合治疗似乎是可行的。
