Supplementary Material for: Temporary Severe Neutropenia during Administration of Atezolizumab: A Novel Case Report

Here we describe a case of temporary severe neutropenia after atezolizumab monotherapy and its treatment course. Atezolizumab monotherapy was introduced as a 6th line treatment for a man in his late 60s who was diagnosed with stage Ⅳ lung adenocarcinoma. The first treatment cycle was administered under hospitalization, and the patients presented with a fever of 37.8°C on the first day. The fever resolved after administration of acetaminophen and naproxen, and the white blood cell count, neutrophil count, and other white blood cell fractions were normal. However, grade 3 leukopenia and grade 4 neutropenia appeared at the beginning of the third cycle, and the treatment was suspended. After treatment, monocytes in the leukocyte fraction increased from approximately 10% to 25.6%. Lenograstim 100 μg subcutaneous injection and oral levofloxacin 500 mg once daily were started of onset of neutropenia, and he was hospitalized on the next day. Laboratory findings upon admission showed significant improvement to 5300/µl for leukocytes and 3376/µl for neutrophils. Lenograstim was discontinued, with no further decrease in the neutrophil counts. Atezolizumab therapy was resumed and there was no further reduction in leukocytes, neutrophils, or leukocyte fractions over about 2-year period. Concomitant drugs were maintained during atezolizumab treatment, suggesting that they did not induce neutropenia. In conclusion, we observed temporary severe neutropenia during atezolizumab monotherapy. Neutrophil recovery with cautious monitoring has enabled longer efficacy. We should consider temporary symptom occurrence in cases of haematological immune-related adverse events.

本研究报告1例阿替利珠单抗（atezolizumab）单药治疗后出现暂时性重度中性粒细胞减少症的病例及其诊疗经过。该患者为60余岁男性，确诊Ⅳ期肺腺癌，阿替利珠单抗单药治疗作为其第六线治疗方案予以应用。首周期治疗于住院期间实施，患者于治疗首日出现体温37.8℃的发热症状。予对乙酰氨基酚（acetaminophen）与萘普生（naproxen）治疗后发热消退，彼时白细胞计数、中性粒细胞计数及其他白细胞分类均处于正常范围。但在第三周期治疗起始时，患者出现3级白细胞减少症与4级中性粒细胞减少症，遂暂停治疗。经干预后，白细胞分类中的单核细胞占比从约10%升高至25.6%。中性粒细胞减少症确诊后，即刻予来格司亭（lenograstim）100μg皮下注射，以及每日1次口服左氧氟沙星（levofloxacin）500mg治疗，患者于次日入院。入院时实验室检查结果显示白细胞计数与中性粒细胞计数显著改善，分别达5300/µl与3376/µl。遂停用来格司亭，此后中性粒细胞计数未再出现下降。后续恢复阿替利珠单抗治疗，在约2年的随访周期内，患者白细胞、中性粒细胞及白细胞分类未再出现降低情况。阿替利珠单抗治疗期间，合并用药方案保持恒定，提示上述合并用药并未诱发中性粒细胞减少症。综上，本病例证实阿替利珠单抗单药治疗过程中可出现暂时性重度中性粒细胞减少症。通过谨慎监测实现中性粒细胞恢复，可保障患者获得更持久的治疗获益。对于血液系统免疫相关不良事件，应警惕暂时性症状的发生。