PK course contents were perceived to lack depth and relevance to practice, and pharmacist had no experiential training that included aspects of PK. These, and other issues, result in poor application of PK in practice.
There has been less volume of literature focusing on the Immune-related Hematological Adverse Drug Events (Hem-irAEs) of Immune Checkpoint Inhibitors (ICPis) in cancer patients. Furthermore, there has been no consensus about the management of hematological toxicity from immunotherapy in the recently published practice guidelines by the European Society for Medical Oncology (ESMO). We conducted a systematic review of case reports/series to describe the diagnosis and management of potentially rare and unrecognized Hem-irAEs. We searched Medline, OVID, Web of Science for eligible articles. Data were extracted on patient characteristics, Hem-irAEs, and management strategies. We performed quality assessment using the Pierson-5 evaluation scheme and causality assessment using the Naranjo scale. Our search retrieved 49 articles that described 118 cases. The majority of patients had melanoma (57.6%) and lung cancer (26.3%). The most common Hem-irAEs reported with ICPis (such as nivolumab, ipilimumab, and pembrolizumab) were thrombocytopenia, hemolytic and aplastic anemias. Less reported adverse events included agranulocytosis and neutropenia. Steroids were commonly used to treat these adverse events with frequent success. Other used strategies included intravenous immunoglobulins (IVIG), rituximab, and transfusion of blood components. The findings of this review provide more insights into the diagnosis and management of the rarely reported Hem-irAEs of ICPis.
Immune checkpoint inhibitors (ICIs)—anti-programmed death-1 (PD-1) and their ligands (PD-L1 and PD-L2) have become widely used in the treatment of several malignancies. Many immune-related adverse events (irAEs) have been linked to these agents. Nonetheless, tuberculosis (TB) reactivation during their use is increasingly recognized and reported. Herein, we present a 58-year-old lady with advanced non-small cell lung cancer (NSCLC) ALK-negative, EGFR wild, and PD-L1 immune histochemistry (IHC) strongly positive in 95% of tumor cells, on ongoing treatment with Pembrolizumab as a first-line monotherapy. Our patient presented with 1-week history of productive cough and high-grade fever. Further workup yielded the diagnosis of pulmonary tuberculosis after her Pembrolizumab sixth cycle with positive AFB smear and TB PCR from BAL (rifampin resistance not detected), with negative HIV status. Hence, immunotherapy was held, and patient was commenced on anti-TB regimen. History revealed contact with active TB patient over the past decade, without previous documentation of latent TB or previous TB infection. Her sputum AFB smear remained persistently positive 4 weeks through anti-TB regimen course. Later, the patient was discharged after her sputum was cleared from AFB (two negative sets). In light of pembrolizumab mechanism of action as an immune checkpoint inhibitor, we suspected its implication on reactivating latent TB which was observed in our patient demonstrating features of pulmonary tuberculosis. She was not re-challenged with Pembrolizumab following TB diagnosis.
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