Teclistamab in combination with daratumumab and lenalidomide in multiple myeloma (MajesTEC-2 study)

Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.

A Comparison of Local-and Foreign-funded Hydropower Station Construction in Nepal based on Remote Sensing

International investors in large infrastructure projects face numerous risks. To explore this issue, this paper compares the development of two hydropower stations in Rasuwa District, Nepal: Upper Trishuli 3A, which is fully funded by a Chinese government bank, and Rasuwagadhi, which is fully funded by local government banks. The construction of these two plants was compared between 2012 and 2020 using a visual interpretation method to extract data on roads, buildings, dams, and vehicles from 1-m-resolution remote sensing imagery. Two methods were used to compare the environmental impacts of each plant. Landsat 7/8 30-m imagery was used to monitor changes in the normalized difference vegetation index around the Upper Trishuli 3A hydropower station from 2012 to 2020 and around the Rasuwagadhi hydropower station from 2014 to 2020. Then, 1-m-resolution imagery was used to observe land-cover differences in these areas and time periods. The results indicate that: (1) despite vari-ous challenges, such as geological disasters, the COVID-19 pandemic, and a blockade by the Indian government, there was no difference in construction progress between the two hydropower stations. (2) The Upper Trishuli 3A Hydropower Station was associated with better environmental protection work, as there were continuous declines in vegetation growth near Rasuwagadhi and increased overall vegetation growth near Upper Trishuli 3A. (3) Energy projects funded by the Belt and Road Initiative have benefited developing countries enormously. Finally, local conditions should be thoroughly investigated during the construction of foreign-funded power stations. © 2022, Editorial office of Journal of Resources and Ecology. All rights reserved.

Operation Status Comparison Monitoring of China’s Southeast Asian Industrial Parks before and after COVID-19 Using Nighttime Lights Data

COVID-19 has had a huge impact on many industries around the world. Internationallyfunded enterprises have been greatly affected by COVID-19 prevention and control measures, such as border controls. However, few studies have examined the impact of COVID-19 on internationally-funded enterprises. To this end, this paper considered 12 of China’s industrial parks situated in Southeast Asia, while comparing the operation status before and after the outbreak of COVID-19 based on remote sensing of nighttime lights (NTL). The NTL is generally used as a proxy for economic activity. First, six parameters were proposed to quantify and monitor the operation status based on NTL data. Subsequently, these parameters were calculated for the parks and for 10 km buffer zones surrounding them to analyze the differences in operating conditions. The results showed that (1) despite the negative impact of COVID-19, 9 out of the 12 parks had a mean NTL greater than 1, indicating that these parks are in better operating condition in 2020 than 2019;(2) 7 out of the 10 km buffer zones around the parks showed a decline in mean NTL. Only three parks showed a decline in mean NTL. The impact of COVID-19 on surrounding areas was greater than the impact on parks. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

The Practice and Exploration of the Pharmacy Counseling Services on Internet-based Medicine Model during the Period of Coronavirus Disease 2019

OBJECTIVE: To explore the novel models of internet-based pharmacy services during the period of coronavirus disease 2019 (COVID-19). METHODS: The process specification, management system, qualification and quality control were discussed and astablished. Retrieving 2-month of internet pharmacy counseling records, and conducting statistical analysis on the relevant information, which includes the counseling content, drug types, numbers, cases and patient evaluation survey. RESULTS: This new model built an internet pharmacy counseling platform in Peking Union Medical College Hospital (PUMCH) on March 2020. Relevant systems and standardized processes has be established. After the implementation of the internet-specific pharmacy counseling service, a total of 615 qualified counseling records were collected by April 12, 2020. The number of online pharmacists, the numbers of counseling, daily pharmacist visits have increased continuously. CONCLUSION: In conclusion, the implementation of internet pharmacy counseling services during the period of coronavirus disease 2019 (COVID-19) solves the drug-related demands from patients as well as reduces the potential risk of cross-infections among patients. This model contributes to the establishment of a series of new pharmacy services to fight against the COVID-19. In addition, it also plays an important role in helping specialist pharmacists provide convenient, patient-centered pharmacy services.