Ipilimumab and early signs of pulmonary toxicity in patients with metastastic melanoma: a prospective observational study
Ipilimumab and early signs of pulmonary toxicity in patients with metastastic melanoma: a prospective observational study
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DOI：
10.1007/s00262-017-2071-2
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发表时间：
2018-01-01
影响因子：
5.8
通讯作者：
Kohler, Malcolm
中科院分区：
文献类型：
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作者：
Franzen, Daniel;Schad, Karin;Kohler, Malcolm
Ipilimumab是一种免疫检查点抑制剂，已被批准用于治疗恶性黑色素瘤，是一种有前途的抗其他恶性肿瘤药物。有一些来自病例报告的初步证据表明，伊匹单抗治疗可能与肺部副作用有关。然而，来自易普利姆玛相关肺毒性的前瞻性研究的数据仍然很少。在用易普利姆玛治疗之前和期间，对患有转移性黑素瘤的患者进行连续的肺量计和CO扩散能力（DLCO）测量。用力肺活量（FVC）较基线降低>= 10%或DLCO>= 15%被定义为具有临床意义并指示肺毒性。在本研究纳入的71例患者中，分别有6/65（9%）、5/44（11%）和9/38（24%）例患者在治疗开始后3、6和9周出现具有临床意义的肺功能下降。即使在调整年龄、伴随黑色素瘤治疗、进行性肺转移和基线肺功能值后，平均+/- SD DLCO在随访期间也显著降低（较基线为-4.3% +/- 13.6%，p = 0.033）。只有7%的患者报告呼吸道症状。仅1例患者（1.4%）诊断为临床表现的伊匹单抗相关肺炎。DLCO下降可能是亚临床肺部药物毒性的早期指标。因此，治疗期间常规肺功能检查（包括DLCO测量）可能有助于进行风险分层，以筛查易普利姆玛相关肺炎。
Ipilimumab, an immune checkpoint inhibitor, is approved for treatment metastastic melanoma and is a promising agent against other malignancies. There is some preliminary evidence from case reports that ipilimumab treatment may be associated with pulmonary side effects. However, data from prospective studies on ipilimumab- related pulmonary toxicity are still scarce. Serial spirometries and measurements of CO-diffusion capacity (DLCO) in patients with metastatic melanoma before and during treatment with ipilimumab were performed. A reduction from baseline of forced vital capacity (FVC) of >= 10%, or >= 15% of DLCO was defined as clinically meaningful and indicative for pulmonary toxicity. Of 71 patients included in this study, a clinically meaningful lung function decline was registered in 6/65 (9%), 5/44 (11%), and 9/38 (24%) patients after 3, 6, and 9 weeks of treatment initiation, respectively. Even after adjusting for age, concomitant melanoma treatment, progressive pulmonary metastases, and baseline pulmonary function values, mean +/- SD DLCO decreased significantly during follow-up (-4.3% +/- 13.6% from baseline, p = 0.033). Only 7% of patients reported respiratory symptoms. Clinically manifest ipilimumab-related pneumonitis was diagnosed only in one patient (1.4%). DLCO decline maybe an early indicator of subclinical pulmonary drug toxicity. Therefore, routine pulmonary function testing including DLCO measurement during treatment might help for risk stratification to screen for ipilimumab-related pneumonitis.