Outcomes and Toxicities of Programmed Death-1 (PD-1) Inhibitors in Hodgkin Lymphoma Patients in the United States: A Real-World, Multicenter Retrospective Analysis.

BACKGROUND: Although classical Hodgkin lymphoma (cHL) is highly curable, 20%-30% of patients will not be cured with conventional treatments. The programmed death-1 (PD-1) inhibitors (PD-1i) nivolumab and pembrolizumab have been Food and Drug Administration-approved for relapsed/refractory (R/R) cHL. There is limited data on the real-world experience with PD-1i in cHL and it is unknown whether fewer selected patients treated with PD-1i derive benefits similar to those observed in published trials. MATERIALS AND METHODS: We performed a multicenter, retrospective analysis of R/R cHL patients treated with PD-1i in the nontrial setting. The primary objective was to describe progression-free survival (PFS) and overall survival (OS) in this population. Secondary objectives were to characterize response rates, toxicities, discontinuation patterns, and post-PD-1i therapies. RESULTS: The study included 53 patients from nine U.S. centers. Overall response rate (ORR), complete response (CR), and partial response (PR) to PD-1i were 68%, 45%, and 23%, respectively. Twelve-month OS and PFS were 89% and 75%, respectively; median PFS was 29 months. Ninety-six percent of patients with CR continue to respond at a median follow-up of 20 months. Toxicities were similar to those previously described. Seventy percent of patients treated with systemic therapy after PD-1i demonstrated objective responses. CONCLUSION: To our knowledge, this analysis is the first describing real-world experience with PD-1i in cHL patients in the U.S. Here, we demonstrate similar response rates compared to prior studies. The toxicity profile of PD-1i was similar to that seen in previous studies; we further describe toxicity patterns in those with prior autoimmune disease or allogeneic transplant. Post-PD-1i systemic therapies appear active. These results support the effectiveness and tolerability of PD-1i therapy in R/R cHL in a real-world setting. IMPLICATIONS FOR PRACTICE: Two PD-1 inhibitors have recently been approved for patients with relapsed/refractory classical Hodgkin lymphoma based on results from nonrandomized clinical trials. However, to date, there have been no studies evaluating the effectiveness and toxicity profile of these drugs in the real-world setting in the U.S. The present study demonstrates that patients treated in a real-world context experience similar rates of overall effectiveness compared with published clinical trials. Patients who discontinue PD-1 inhibitors may experience clinical responses to subsequent treatment with systemic chemotherapy or targeted therapy. This study provides clinicians with further insight into the effectiveness and tolerability of PD-1 inhibitors and suggests that when patients progress while on these drugs, conventional systemic chemotherapy may be an effective treatment option.

Laboratory Evaluation of Different Insecticides against Hibiscus Mealybug, Maconellicoccus hirsutus (Hemiptera: Pseudococcidae).

Hibiscus mealybug, Maconellicoccus hirsutus (Hemiptera: Pseudococcidae), is the major pest of many vegetables, fruits, crops, and ornamental plants causing losses to the farmers and its control has been an issue of significance in the pest management. This study was aimed at evaluating different concentrations (0.06%, 0.1%, and 0.14%) of Telsta, Advantage, Talstar, Imidacloprid, and their mixtures against hibiscus mealybug in the Laboratory of Systematics and Pest Management at University of Gujrat, Pakistan. The toxic effect was evaluated in the laboratory bioassay after 24 and 48 h of the application of insecticides. The highest mortality (95.83%) was shown by Talstar and Talstar + Imidacloprid at the concentration of 0.14% after 48 h followed by Advantage + Talstar with 87.50% mortality at 0.14% concentration after 48 h of application. The study also showed that the least effective treatment observed was Advantage + Telsta with no mortality after 24 h and 25% mortality after 48 h at 0.14% concentration. The study revealed that the concentration 0.14% was highly effective in lowering the mealybug population and insecticide mixtures were effective in reducing mealybug density. The study emphasizes the use of such insecticide mixtures to develop better management strategy for mealybug populations attacking ornamental plants. However effects of such insecticide mixtures on other organisms and biological control agents should be checked under field conditions.

Paradoxical respiratory sinus arrhythmia due to a large thoracic empyema in an ambulatory patient.

We report a case of paradoxical respiratory sinus arrhythmia (PRSA) caused by a retro-cardiac empyema in an ambulatory patient. The case describes the dynamics and deleterious impact of PRSA on cardio-respiratory cycle, its electrocardiographic, radiologic and echocardiographic findings. Furthermore, it discusses a probable mechanism of paradoxical respiratory sinus arrhythmia in the setting of a retrocardiac mass and suggests a need for physicians to check for the changes in ventilation perfusion mismatch and rise in physiological dead space in such patients. In conclusion, to the best of our knowledge, this is the first documented report of paradoxical respiratory sinus arrhythmia in an ambulatory, non-anesthetized spontaneously breathing patient.