Radiologic Features of Pneumonitis Associated With Nivolumab in Non-Small-Cell Lung Cancer and Malignant Melanoma

Baba, Tomohisa; Sakai, Fumikazu; Kato, Terufumi; Kusumoto, Masahiko; Kenmotsu, Hirotsugu; Sugiura, Hiroaki; Tominaga, Junya; Oikado, Katsunori; Sata, Masafumi; Endo, Masahiro; Yanagawa, Noriyo; Sasaki, Shin‐ichi; Iwasawa, Tae; Saito, Yoshinobu; Fujiwara, Yutaka; Ohe, Yuichiro; Yamazaki, Naoya; Sakamoto, Takahiko; Koshiba, Takashi; Kuwano, Kazuyoshi

doi:10.2217/fon-2019-0102

Cited by 39 publications

(66 citation statements)

References 20 publications

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“…Although it is difficult to distinguish between the two forms of pneumonitis, ICI-related pneumonitis has been reported to exhibit some specific radiological features, such as ground glass opacities (GGOs), a cryptogenic organizing pneumonia-like appearance, and interstitial pneumonia pattern [18]. Baba T et al [19] reported that GGOs around the tumor (peritumoral infiltration) were a characteristic finding in pneumonitis induced by nivolumab.…”

Section: Discussionmentioning

confidence: 99%

Clinical and radiation dose-volume factors related to pneumonitis after treatment with radiation and durvalumab in locally advanced non-small cell lung cancer

et al. 2020

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Introduction Durvalumab has been shown to confer a survival benefit after definitive chemoradiotherapy in the patients with locally advanced non-small cell lung cancer, but no studies have attempted to identify risk factors for pneumonitis after durvalumab therapy. The purpose of this study was to investigate associations between clinical and radiation dose-volume factors, and the severity of pneumonitis. Methods We retrospectively assessed the cases of 30 patients who had been started on durvalumab therapy between July 2018 and February 2019. In this study we evaluated the percentage of lung volume receiving radiation dose in excess of 20 Gy (V20) as radiation dose-volume factor. We compared V20 and some baseline factors between a grade 0 or 1 (Gr 0/1) pneumonitis group and a grade 2 or more (≥Gr 2) pneumonitis group, and we performed a logistic regression analysis to establish the associations between variables and ≥ Gr 2 pneumonitis. Results Pneumonitis had developed in 22 patients (73.3%): Gr 1/2/3-5 in 8 (26.7%)/14 (46.7%) /0 (0%), respectively. The difference in V20 between the Gr 0/1 group and Gr 2 group (median: 20.5% vs. 23.5%, p = 0.505) was not statistically significant, and thus V20 was not a risk factor for Gr 2 pneumonitis (odds ratio: 1.047, p = 0.303). None of the clinical factors, including sex, age, smoking history, presence of baseline pneumonitis, type of radiation therapy, location of lesion and facility, were risk factors. Conclusions Our study suggest that the severity of pneumonitis after durvalumab is unrelated to V20 or any of the clinical factors assessed in this study.

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Section: Discussionmentioning

confidence: 99%

Clinical and radiation dose-volume factors related to pneumonitis after treatment with radiation and durvalumab in locally advanced non-small cell lung cancer

et al. 2020

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“…16,17 ICI-ILD often occurs earlier in lung cancer, with a median of 2.1 months after ICI treatments, 1 and presents as several radiologic patterns. 18 A total of 70-80% of ICI-ILD cases can be controlled through the prompt initiation of a high dose of steroids. 19 In our case, the male patient had a long history of smoking and his chest CT showed severe pre-existing interstitial lung disease, which might lead to the occurrence of ILD after 15 cycles of nivolumab treatment.…”

Section: Discussionmentioning

confidence: 99%

<p>Immune Checkpoint Inhibitor Therapy Achieved Complete Response for Drug-Sensitive<em> EGFR/ALK</em> Mutation-Negative Metastatic Pulmonary Large-Cell Neuroendocrine Carcinoma with High Tumor Mutation Burden: A Case Report</p>

Zhang¹,

Sun²,

Miao³

et al. 2020

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Large-cell neuroendocrine lung carcinoma (LCNELC) is classified into lung neuroendocrine tumors according to WHO 2015 classification guidelines and represents approximately 3% of all lung cancer. Because of the rarity of LCNELC, there is a lack of prospective studies guiding treatment. Here, we report a case of a patient with pT2aN2M0 stage IIIA LCNELC (drug-sensitive EGFR/ALK mutation-negative, PD-L1-negative but tumor mutation burden (TMB) high), who progressed rapidly after surgery but achieved a complete response to subsequent immune checkpoint inhibitor (ICI) therapy. The concentration of circulating tumor DNA (ctDNA) following the treatment course strongly reflects the response to ICI therapy. This report highlights the efficacy of ICI treatment in metastatic LCNELC patients with a high TMB and suggests that ctDNA analysis in detecting molecular residual disease may facilitate the personalization of ICI therapy.

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“…Some case reports have reported the acute exacerbation of underlying infection, such as pulmonary tuberculosis, during anti-PD-1 antibody therapy. [20][21][22] Retrospective studies also demonstrated increased risk of infection in patients receiving ICIs along with immunosuppressive agents, including corticosteroids and infliximab, as well as in patients with concomitant diabetes mellitus. 23 24 However, because the subjects with underlying infection, uncontrolled diabetes mellitus or the concomitant use of immunosuppressive agents were excluded based on the exclusion criteria of each phase I study, these events were not recorded in our study.…”

Section: Discussionmentioning

confidence: 99%

Infection risk with PI3K-AKT-mTOR pathway inhibitors and immune checkpoint inhibitors in patients with advanced solid tumours in phase I clinical trials

et al. 2020

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BackgroundPatients undergoing chemotherapy are known to be at risk for infection from myelosuppression by cytotoxic agents (CTAs) or immunosuppressive effects from mTOR inhibitors. The infection risk of newly developed anticancer agents has not been fully evaluated. It remains unknown how T-cell activation induced by immune checkpoint inhibitors (ICIs) relates to infection.MethodsWe retrospectively examined infection risk in patients with cancer treated with investigational agents in a phase I study. The investigational agents were classified into four groups: CTA, phosphatidylinositol 3 kinase/Akt/mammalian target of rapamycin inhibitor (PAM), molecular targeted agent (MTA) and ICI. All infection-related adverse events (AEs) during treatment were recorded. We compared the CTA, PAM and ICI with MTA, because MTA are already considered low risk and were used in the largest number of patients.ResultsA total of 641 patients were enrolled: 35 CTAs (5.5%), 61 PAMs (9.5%), 445 MTAs (69.4%) and 100 ICIs (15.6%). Among all patients, 132 (20.6%) experienced infection-related AEs and 46 (7.2%) developed 50 ≥grade 3 infection-related AEs. In any infection-related AEs, the ORs compared with MTAs were 2.19 (95% CI 1.03 to 4.66) for CTAs, 3.55 (95% CI 2.02 to 6.24) for PAMs and 1.05 (95% CI 0.60 to 1.85) for ICIs, respectively. In time to the first infection-related AE analysis, the risks for any infection-related AE from CTAs and PAMs were higher than those from MTAs (HR 1.84 (95% CI 0.82 to 4.11); p=0.05 and 3.96 (95% CI 2.18 to 7.22); p<0.001). The risk from ICIs was not significantly different from that of MTAs (HR 0.71 (95% CI 0.46 to 1.10); p=0.19).ConclusionOur results validate that PAMs and CTAs carry a higher infection risk in patients with advanced solid tumours compared with MTAs. We suggest that the infection risk of ICIs is a similar infection risk to MTAs.

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Radiologic Features of Pneumonitis Associated With Nivolumab in Non-Small-Cell Lung Cancer and Malignant Melanoma

Cited by 39 publications

References 20 publications

Clinical and radiation dose-volume factors related to pneumonitis after treatment with radiation and durvalumab in locally advanced non-small cell lung cancer

Clinical and radiation dose-volume factors related to pneumonitis after treatment with radiation and durvalumab in locally advanced non-small cell lung cancer

<p>Immune Checkpoint Inhibitor Therapy Achieved Complete Response for Drug-Sensitive<em> EGFR/ALK</em> Mutation-Negative Metastatic Pulmonary Large-Cell Neuroendocrine Carcinoma with High Tumor Mutation Burden: A Case Report</p>

Infection risk with PI3K-AKT-mTOR pathway inhibitors and immune checkpoint inhibitors in patients with advanced solid tumours in phase I clinical trials

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