Pembrolizumab-Associated Stevens-Johnson Syndrome in a Patient With Metastatic Non-small Cell Lung Cancer: A Case Report.

Pembrolizumab is a monoclonal antibody that binds to the programmed cell death-1 (PD-1) receptor and is approved for the treatment of several malignancies. We present a rare case of Stevens-Johnson syndrome (SJS) occurring in a 75-year-old female 14 days after receiving the first dose of pembrolizumab therapy to treat stage IV non-small cell carcinoma of the lungs with metastasis to the brain. Although pruritus and papular, erythematous rashes are documented after its use, severe reactions such as SJS and toxic epidermal necrolysis (TEN) are rarely seen in clinical practice. In addition to supportive care, the patient also received intravenous immunoglobulin (IVIG) and corticosteroid therapy and responded well to the therapy. Nearly complete re-epithelialization was achieved four weeks after the start of skin lesions. This case highlights a rare phenomenon of SJS- and TEN-associated adverse reactions following treatment with pembrolizumab.

Metabolic syndrome is independently associated with improved overall survival to first-line therapy with immune checkpoint inhibitors in non-small cell lung cancer.

Background: Many co-existing medical conditions may affect the outcome in patients treated with immune checkpoint inhibitors for advanced cancer. There is currently not any information on whether metabolic syndrome (MetS) impacts the clinical outcome in patients treated with immune checkpoint inhibitors (ICIs) for advanced non-small cell line cancer (NSCLC). Methods: We carried out a single-center retrospective cohort study to determine the effects of MetS on first-line ICI therapy in patients with NSCLC. Results: One hundred and eighteen consecutive adult patients who received first-line therapy with ICIs and had adequate medical record information for the determination of MetS status and clinical outcomes were included in the study. Twenty-one patients had MetS and 97 did not. There was no significant difference between the two groups in age, gender, smoking history, ECOG performance status, tumor histologic types, pre-therapy use of broad-spectrum antimicrobials, PD-L1 expression, pre-treatment neutrophil:lymphocyte ratio, or proportions of patients who received ICI monotherapy or chemoimmunotherapy. With a median follow-up of 9 months (range 0.5-67), MetS patients enjoyed significantly longer overall survival (HR 0.54, 95% CI: 0.31-0.92) (p = 0.02) but not progression-free survival. The improved outcome was only observed in patients who received ICI monotherapy and not chemoimmunotherapy. MetS predicted for higher probability of survival at 6 months (p = 0.043) and 12 months (p = 0.008). Multivariate analysis indicated that, in addition to the known adverse effects of use of broad-spectrum antimicrobials and the beneficial effects of PD-L1 (Programmed cell death-ligand 1) expression, MetS was independently associated with improved overall survival but not progression-free survival. Conclusions: Our results suggest that MetS is an independent predictor of treatment outcome in patients who received first-line ICI monotherapy for NSCLC.

A Systematic Review of Tafamidis in Patients With Transthyretin Amyloid Cardiomyopathy.

Transthyretin amyloid cardiomyopathy disease burden is increasing daily due to advancements in diagnostic and imaging modalities in the modern world. Tafamidis is one of many therapeutic options. The main objective of this review is to study the role of Tafamidis in slowing the progression of transthyretin cardiomyopathy (TTR-CM) by analyzing randomized controlled trials (RCTs) and non-RCTs of Tafamidis. We searched for published papers of Tafamidis in the English language in electronic databases like Google Scholar, PubMed, Cochrane Library, and PubMed Central. We imported the resulting articles from our search to Mendeley software. Four reviewers removed the duplicates and performed title and abstract screening of the articles. The same reviewers obtained the full-text of relevant articles and did full-text screening based on eligibility criteria. Finally, five reviewers performed a quality assessment of RCTs using the Cochrane risk of bias assessment and of non-RCTs by a checklist prepared by Downs and Black. Any disagreements about any process were resolved by a discussion with other authors. One RCT and five non-RCTs of Tafamidis were included in this systematic review. From the non-RCTs, stability was observed in different parameters like echocardiographic findings, cardiac biomarkers, and ECG in patients with transthyretin cardiomyopathy during the study duration with Tafamidis. ATTR-ACT (Tafamidis in Transthyretin Cardiomyopathy Clinical Trial) trial demonstrated reduction of cardiovascular events and all-cause mortality in the Tafamidis group in comparison to placebo. In both RCT and non-RCTs, Tafamidis was established as a safe and tolerable drug for patients with TTR-CM. Our study proved the role of Tafamidis in reducing cardiovascular events, all-cause mortality, and the progression of cardiac disease in TTR-CM patients. In addition to five non-RCTs, current evidence is based on the findings of only one RCT of Tafamidis. Hence, evidence from additional RCTs is required to strongly support the stability of parameters like echocardiographic findings, cardiac biomarkers, and ECG with Tafamidis use.