Development and Evaluation of a Quantitative Systems Pharmacology Model for Mechanism Interpretation and Efficacy Prediction of Atezolizumab in Combination with Carboplatin and Nab-Paclitaxel in Patients with Non-Small-Cell Lung Cancer.

Immunotherapy has shown clinical benefit in patients with non-small-cell lung cancer (NSCLC). Due to the limited response of monotherapy, combining immune checkpoint inhibitors (ICIs) and chemotherapy is considered a treatment option for advanced NSCLC. However, the mechanism of combined therapy and the potential patient population that could benefit from combined therapy remain undetermined. Here, we developed an NSCLC model based on the published quantitative systems pharmacology (QSP)-immuno-oncology platform by making necessary adjustments. After calibration and validation, the established QSP model could adequately characterise the biological mechanisms of action of the triple combination of atezolizumab, nab-paclitaxel, and carboplatin in patients with NSCLC, and identify predictive biomarkers for precision dosing. The established model could efficiently characterise the objective response rate and duration of response of the IMpower131 trial, reproducing the efficacy of alternative dosing. Furthermore, CD8+ and CD4+ T cell densities in tumours were found to be significantly related to the response status. This significant extension of the QSP model not only broadens its applicability but also more accurately reflects real-world clinical settings. Importantly, it positions the model as a critical foundation for model-informed drug development and the customisation of treatment plans, especially in the context of combining single-agent ICIs with platinum-doublet chemotherapy.

Efficacy of caspofungin combined with clindamycin for Pneumocystis jirovecii pneumonia in a systemic lupus erythematosus patient: A case report and literature review.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection with a difficult diagnosis, rapid progression, high mortality rate and poor prognosis. The primary treatment and prevention of PCP is trimethoprim/sulfamethoxazole (TMP/SMZ). However, there are many cases of intolerance or resistance to the drug, so the convenient and effective alternatives are deficient. CASE PRESENTATION: A 66-year-old woman who took an immunosuppressive agent for a long time was diagnosed with PCP. Poor compliance of treatment was found out after monitoring TMP/SMZ plasma concentrations in this patient. She stopped taking the drug herself because of nausea. As a result of intolerance to TMP/SMZ, caspofungin combined with clindamycin were chosen to continue anti-PCP treatment in this patient. She finally improved and discharged from hospital. CONCLUSION: The new combination of caspofungin and clindamycin may be beneficial for patients with PCP who have failed treatment or are intolerant of TMP/SMZ. In addition, the trend of ß-glucan levels can be a predictor of therapeutic efficacy in PCP.