Characterization of pre- and on-treatment soluble immune mediators and the tumor microenvironment in NSCLC patients receiving PD-1/L1 inhibitor monotherapy.

BACKGROUND: Despite the favorable therapeutic efficacy observed with ICI monotherapy, the majority of non-small cell lung cancer (NSCLC) patients do not respond. Therefore, identifying patients who could optimally benefit from ICI treatment remains a challenge. METHODS: Among 183 patients with advanced or recurrent NSCLC who received ICI monotherapy, we analyzed 110 patients whose pre- and post-treatment plasma samples were available. Seventy-three soluble immune mediators were measured at ICI initiation and 6 weeks later. To identify useful biomarkers, we analyzed the association of pre-treatment levels and on-treatment changes of soluble immune mediators with survival of patients. The associations of pre-treatment or on-treatment biomarkers with irAE development, PD-L1 expression, CD8+ TIL density, and neutrophil to lymphocyte ratio (NLR) were also analyzed. RESULTS: Univariate analysis showed that pre-treatment biomarkers included 6 immune mediators, whereas on-treatment biomarkers included 8 immune mediators. Multivariate analysis showed that pre-treatment biomarkers included 4 immune mediators (CCL19, CCL21, CXCL5, CXCL10), whereas on-treatment biomarkers included 5 immune mediators (CCL7, CCL19, CCL23, CCL25, IL-32). IrAE development was associated with on-treatment change in CCL23. PD-L1 expression was associated with the pre-treatment levels of TNFSF13B and the on-treatment change in CCL25. CD8+ TIL density was associated with the pre-treatment CXCL10 level, whereas NLR was correlated with pre-treatment levels of CCL13 and CCL17. CONCLUSION: We identified several soluble immune mediators as pre-treatment and on-treatment biomarkers of survival in patients with NSCLC treated with ICI monotherapy. Some of these biomarkers were associated with other possible predictors, including irAE development, PD-L1 expression, CD8+ TIL density and NLR. Further large-scale studies are needed to establish biomarkers for patients with NSCLC who received ICI monotherapy.

Case Series of Patients with Coronavirus Disease 2019 Pneumonia Treated with Hydroxychloroquine.

The efficacy of hydroxychloroquine (HCQ) therapy, a previous candidate drug for coronavirus disease 2019 (COVID-19), was denied in the global guideline. The risk of severe cardiac events associated with HCQ was inconsistent in previous reports. In the present case series, we show the tolerability of HCQ therapy in patients treated in our hospital, and discuss the advantages and disadvantages of HCQ therapy for patients with COVID-19. A representative case was a 66-year-old woman who had become infected with severe acute respiratory syndrome coronavirus 2 and was diagnosed as having COVID-19 pneumonia via polymerase chain reaction. She was refractory to treatment with levofloxacin, lopinavir, and ritonavir, while her condition improved after beginning HCQ therapy without severe side effects. We show the tolerability of HCQ therapy for 27 patients treated in our hospital. In total, 21 adverse events occurred in 20 (74%) patients, namely, diarrhea in 11 (41%) patients, and elevated levels of both aspartate aminotransferase and alanine transaminase in 10 (37%) patients. All seven grade ≥ 4 adverse events were associated with the deterioration in COVID-19 status. No patients discontinued HCQ treatment because of HCQ-related adverse events. Two patients (7%) died of COVID-19 pneumonia. In conclusion, HCQ therapy that had been performed for COVID-19 was well-tolerated in our case series.

Successful Treatment of a Patient with Drug-Refractory Rheumatoid Arthritis-Associated Interstitial Lung Disease with Upadacitinib: A Case Report.

Insufficient evidence exists regarding the efficacy of Janus kinase inhibitors (JAKis), a class of targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs), in the treatment of rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). Herein, we present a case of RA-ILD refractory to previous treatments that exhibited favorable response to upadacitinib. A 69-year-old man, former smoker, was diagnosed with RA-ILD based on persistent symmetric polyarthritis, elevated C-reactive protein levels and erythrocyte sedimentation rate, reduced diffusing capacity for carbon monoxide/alveolar volume (DLCO 69.9%), and bilateral ground-glass attenuation with traction bronchiectasis, predominantly in the lower lung lobe. Initial treatment with oral prednisolone and methotrexate was started; however, the patient showed worsening dyspnea, chest high-resolution computed tomography abnormalities, and decreased pulmonary function. The dose of prednisolone was increased, and methotrexate was shifted to tacrolimus; however, tacrolimus was eventually discontinued because of renal dysfunction. Subsequent treatment changes included abatacept followed by intravenous cyclophosphamide, but ILD activity continued to worsen and met the criteria of progressive pulmonary fibrosis. Approximately 4.5 years after the RA diagnosis, dyspnea, radiological abnormalities, and DLCO improved following treatment switch to upadacitinib, one of JAKis. JAKi therapy may have potential as a treatment option for refractory RA-ILD.

A Case in which Eosinophilic Meningoencephalitis Occurred during Oral Corticosteroid Tapering and after Switching from Anti-IL-5 to Anti-IgE Treatment.

A 49-year-old man with severe eosinophilic asthma, sinusitis, and esophagitis was admitted with a sudden severe headache. The patient was diagnosed with eosinophilic meningoencephalitis based on frontotemporal abnormalities on brain magnetic resonance imaging and high eosinophil counts in the cerebrospinal fluid. His allergic-disease control levels were poor, requiring regular oral corticosteroid (OCS) use. He was switched from anti-interleukin (IL)-5 to anti-IgE therapy because of worsening urticaria and asthma symptoms during OCS tapering. We suspect this was a case of complex eosinophilic meningoencephalitis caused by the combination of OCS tapering and anti-IL-5 therapy cessation that acquired anti-IgE antibody sensitization based on positive drug-induced lymphocyte stimulation test results.

Oral Colchicine and Low-Dose Aspirin Combination Therapy for Non-elderly, Non-severe, Early Time From Onset, Adult Outpatients with Coronavirus Disease 2019 (COVID-19) during "The Fifth Pandemic Wave" in Japan.

BACKGROUND: Treatment with antiviral drugs for non-severe, early time from onset, adult outpatients with Coronavirus Disease 2019 (COVID-19) had not been established in 2021. However, some new variants of SARS-CoV-2 had caused rapid exacerbation and hospitalization among non-elderly outpatients with COVID-19, contributing to widespread crises within healthcare systems. METHODS: From July to October 2021, we urgently assessed a therapeutic program using oral colchicine (1.0 mg loading dose, followed approximately half a day later by 0.5 mg twice daily for 5 days, and then 0.5 mg once daily for 4 days) and low-dose aspirin (100 mg once daily for 10 days), for non-elderly, non-severe, early time from onset, adult outpatients with COVID-19. To verify its effectiveness, we set loxoprofen as a control arm, and com parison of these two arms was performed. The primary outcomes were hospitalization, criticality, and death rates. RESULTS: Thirty-eight patients (23 receiving colchicine and low-dose aspirin [CA]; 15 receiving loxoprofen [LO]) were evaluated. Hospitalization rate was lower in the CA group (1/23; 4.3%) than in the LO group (2/15; 13.3%); however, no significant difference was found between the two groups (p=0.34). No critical cases, deaths, or severe adverse events were found in either group. CONCLUSIONS: Our CA regimen did not show superiority over LO treatment. However, our clinical experience should be recorded as part of community health care activities carried out in Kurume City against the unprece dented COVID-19 pandemic.

A Rare Case of Diffuse Bilateral Minute Pulmonary Meningothelial-like Nodules Increasing over the Short Term and Resembling Metastatic Lung Cancer.

A 54-year-old woman was referred to our hospital because computed tomography (CT) revealed multiple lung nodules during a health checkup. The nodules were up to 5 mm in diameter and randomly distributed in both lungs, appearing ring-shaped. No clinical symptoms were present. However, the nodes proliferated, and multiple lung metastases could not be ruled out, so a biopsy was performed to establish a diagnosis. She was diagnosed with minute pulmonary meningothelial-like nodules (MPMNs), and her condition had not deteriorated at the latest follow-up. Although rare, MPMNs can proliferate for a short time, but a biopsy to exclude malignant causes is essential.

Granulomatous Lymphocytic Interstitial Lung Disease in Multiple Myeloma.

An 82-year-old woman complained of recurring cough and shortness of breath and was diagnosed with progressive multiple myeloma (MM). Chest computed tomography (CT) revealed bilateral ground-glass opacity and interlobular septal thickening predominantly in the lower lung zones. Histopathologic findings obtained by a transbronchial lung cryobiopsy (TBLC) revealed alveolitis and granulomas consistent with granulomatous-lymphocytic interstitial lung disease (GLILD). Aggressive chemotherapy for MM contributed to the improvement in respiratory symptoms and abnormal chest CT findings. In cases of MM with lung abnormalities, the possibility of GLILD must be ruled out, and a TBLC should be considered to attain an accurate diagnosis.

Pazopanib for treating rhabdomyosarcoma in adult patients with poor performance status: A case report.

Rhabdomyosarcoma (RMS) is a common soft tissue sarcoma usually observed in children. However, RMS rarely occurs in adults. The prognosis of adult RMS is poor and a standard chemotherapy regimen has not yet been established. Herein, we report the case of a 60-year-old Japanese woman with primary anterior mediastinal alveolar RMS (T3N0M0, stage III). The tumor increased aggressively despite first-line treatment with doxorubicin (60 mg/m2 every 3 weeks for 1 cycle) and second-line treatment with eribulin (1.4 mg/m2 every 3 weeks for 2 cycles). Although her shortness of breath and chest tightness worsened as the tumor compressed her heart and left main bronchus, and her performance status (PS) decreased to 3, third-line treatment with pazopanib (800 mg once daily) was commenced. The treatment led to suppression of tumor growth and resulted in 4-month progression-free survival. Therefore, in cases of adult RMS, considering pazopanib treatment as an option may be beneficial, even with previous ineffective treatments or poor PS.