Safety outcomes of pembrolizumab with platinum agent chemotherapy combined with 5-fluorouracil or taxane derivative in head and neck cancer.

INTRODUCTION: For patients with metastatic head and neck squamous cell cancer (HNSCC), the outcomes of pembrolizumab in combination with a platinum agent and taxane as first-line therapy remain unknown. The purpose of this study is to characterize the impact of substituting the 5-fluorouracil (5-FU) backbone for a taxane in this chemoimmunotherapy regimen on safety/tolerability and survival outcomes. METHODS: This was an IRB-approved, single-center, retrospective, active comparator, new-user design study in adult patients with HNSCC treated between January 2018 and September 2021. The primary objective was to assess safety and tolerability of pembrolizumab in combination with a platinum agent and taxane against an active comparator arm of pembrolizumab in combination with a platinum agent and 5-FU. Safety and tolerability were evaluated by assessing differences in overall toxicities, with further secondary analysis evaluating differences in hematologic toxicities and pre-defined non-hematologic toxicities. RESULTS: There was no statistical difference demonstrated with the primary endpoint between the cohorts. Reduced toxicity rates were found in the taxane arm for mucositis and creatinine levels. No grade 4 non-hematologic toxicities were reported. Patients receiving 5-FU were more likely to have dose reductions upfront, discontinue treatment due to intolerances and had significantly higher mucositis. CONCLUSIONS: This study helps to characterize the safety profile and activity of pembrolizumab in combination with a platinum agent and taxane derivative in HNSCC patients. Within our study, substitution of 5-FU with a taxane did not show an increased risk of toxicities, worsened survival, or decreased odds of achieving a response. Mucositis and elevated creatinine rates were significantly reduced within the taxane arm.

Twin-twin transfusion syndrome complicated by single ventricle physiology: A case report.

Clinically significant extrauterine twin-twin transfusion syndrome in conjoined twins is rare and carries a high risk of perinatal mortality. The ensuing postnatal imbalance in circulation across connecting vessels results in hypovolemia in the donor and hypervolemia in the recipient. Data on management and treatment are sparse especially in the setting of a single ventricle congenital heart defect. We present a case of a pair of omphalopagus conjoined twins, one with a single ventricle physiology (Twin B), who developed twin-twin transfusion syndrome shortly after birth. The resulting pathophysiology in the setting of a single ventricle congenital heart defect created added layers of complexity to their management and expedited surgical separation. Shunting from Twin B to Twin A-with an anatomically normal heart-resulted in mal-perfusion and rapid deterioration jeopardizing the health of both twins. In the preoperative course, steps taken to medically optimize the twins prior to surgery and the anesthetic considerations are detailed in this report.

Adherence to National Consensus Guidelines and Association with Clinical Outcomes in Patients with Candidemia.

BACKGROUND: National consensus guidelines outline recommendations for best practices in treating patients with candidemia. This study evaluated the impact of receiving care adherent to the best practice recommendations on clinical outcomes in patients with candidemia. METHODS: This retrospective, multicenter study included patients with candidemia from 2010 to 2015 at 9 hospitals. The primary outcome was the composite of 30-day in-hospital mortality and 90-day candidemia recurrence. Outcomes were compared between those receiving and not receiving care adherent to the guideline recommendations. Inverse probability weights with regression adjustment were utilized to determine the average treatment effect of adherent care on the composite outcome. RESULTS: 295 patients were included with 14.2% meeting criteria for the composite outcome (11.9% mortality and 2.4% recurrence). The average treatment effect of adherent care was not significant (P = .75). However, receiving appropriate initial antifungal treatment and central venous catheter removal were both associated with the composite (average treatment effect of -17.5%, P = .011 and -8.8%, P = .013, respectively). In patients with a source of infection other than the central line, central venous catheter removal was not associated with the composite (P = .95). The most common reason for failure to receive appropriate initial antifungal treatment was omission of the loading dose. CONCLUSIONS: Central venous catheter removal and appropriate initial antifungal treatment were associated with a lower incidence of the composite of mortality and recurrence. Additional studies are needed to determine the optimal duration of therapy following candidemia clearance.

Response to therapeutic monoclonal antibodies for multiple myeloma in African Americans versus whites.

BACKGROUND: Myeloma occurs disproportionately in African Americans, with disparities in outcomes potentially caused by access to care, cytogenetics, and immunity. A gap in knowledge of immune function dissimilarities between African Americans and whites exists. Data for other diseases suggest innate differences in immunity and inflammatory markers, with potential implications for therapeutic monoclonal antibodies reliant on secondary immune activation for activity. METHODS: Patients receiving daratumumab or elotuzumab, lenalidomide, and dexamethasone were retrospectively studied with a primary endpoint of response at 2 (daratumumab) or 4 months (elotuzumab). Secondary endpoints included stable disease or better at the same points, treatment duration, time to best response, and adverse events. RESULTS: Eighty patients were included; baseline characteristics were balanced with the exception of the stage at diagnosis, which was more advanced in African Americans. No statistically significant difference in response was seen: 37.9% in whites versus 11.8% in African Americans with daratumumab (P = .090) and 60% in whites versus 44% in African Americans with elotuzumab (P = .462). There were no differences in the duration of treatment, the time to best response, or adverse events. Common potential immune-related adverse events in both arms were fatigue (39%), back pain (30%), and infusion reactions (40%). Anemia was significantly associated with a response to daratumumab (P = .02); no patients without anemia responded at 2 months, whereas 34.4% of patients with anemia did. CONCLUSIONS: No significant difference in response, duration of treatment, or time to response was seen by race, although a trend toward greater early response rates in whites was observed. In these cohorts, as in other analyses, African American patients tended to present with later stage disease.

Daratumumab and its use in the treatment of relapsed and/or refractory multiple myeloma.

Daratumumab gained initial US FDA approval as fourth-line therapy among relapsed and/or refractory multiple myeloma (RRMM) patients who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), or who are double refractory to a PI and an IMiD. Further combination trials of daratumumab led to FDA approvals in combination with bortezomib and dexamethasone or lenalidomide and dexamethasone for multiple myeloma patients who have received at least one prior therapy. The most recent expansion of the FDA approval of daratumumab comes in combination with pomalidomide and dexamethasone for patients with multiple myeloma that have received ≥2 prior lines of therapy including lenalidomide and a PI. The current manuscript reviews data supporting the efficacy and safety of daratumumab in RRMM.

Docetaxel/Cyclophosphamide-Induced Phototherapy Recall.

Phototherapy recall can occur unexpectedly as a result of treatment with commonly used medications and chemotherapy. These reactions are rare. The recall reaction is an inflammatory response that is triggered by many medications. Cyclophosphamide and docetaxel are widely used chemotherapeutic agents that are useful in the management of many different malignancies. The pathophysiology of phototherapy recall is not clearly understood. This case highlights the need for practitioners to be aware of this potential reaction, even though UV exposure may have occurred in the distant past. We present, to the best of our knowledge, the first phototherapy recall dermatitis that occurred years after UV exposure induced by cyclophosphamide and docetaxel. The frequency of administration of this drug and the profound implications of this adverse effect make this case an important contribution to the medical literature.