A Phase II Study of Venetoclax in Combination With Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma

© 2021 The Authors.[Background]: Venetoclax is a selective BCL-2 inhibitor with clinical activity in relapsed/refractory multiple myeloma (RRMM). Combinations of venetoclax with agents that have complementary mechanisms of action may improve venetoclax efficacy in RRMM. This study evaluated venetoclax with pomalidomide and dexamethasone (VenPd) in RRMM. [Patients and Methods]: This phase II open label study (NCT03567616) evaluated VenPd in patients with RRMM who had received ≥ 1 prior therapy and were refractory to lenalidomide. Venetoclax was administered orally daily for days 1 to 28, pomalidomide was administered orally daily for days 1 to 21, and dexamethasone was administered weekly for each 28-day cycle. The primary objective was to characterize the safety and tolerability of VenPd. The secondary objectives were to evaluate the efficacy and pharmacokinetics. The study was terminated early due to partial clinical hold and decision to pursue biomarker driven strategy. [Results]: Eight patients were enrolled. Patients had a median age of 67.5 years. All patients received 400 mg venetoclax; 4 patients experienced dose-limiting toxicities and the dose was not escalated. All patients had a grade ≥ 3 adverse event, and the most common was neutropenia (n = 6); cytopenias were the most prevalent adverse events. Five patients (63%) had a confirmed response, and the median duration of response was 12.9 months. The median progression-free survival was 10.5 months. [Conclusions]: Given the limited enrollment, no clear safety or efficacy conclusions about VenPd can be drawn. Preliminary safety data, particularly the occurrence of cytopenias, can be used to guide dosing strategies for future combinations of venetoclax with immunomodulatory agents.AbbVie Inc is a private corporation, and funding is not associated with a grant number. Funding information is correct as stated

Plasticity in response to feed availability - does feeding regime influence the relative growth performance of domesticated, wild and hybrid Atlantic salmon Salmo salar parr?

Growth of farmed, wild and F1 hybrid Atlantic salmon parr, Salmo salar, was investigated under three contrasting feeding regimes in order to understand how varying levels of food availability affects relative growth. Treatments consisted of standard hatchery feeding (ad libitum), access to feed for 4h every day, and access to feed for 24h on three alternate days weekly. Mortality was low in all treatments, and food availability had no effect on survival of all groups. The offspring of farmed S. salar significantly outgrew the wild S. salar, while hybrids displayed intermediate growth. Furthermore, the relative growth differences between the farmed and wild S. salar did not change across feeding treatments, indicating a similar plasticity in response to feed availability. Although undertaken in a hatchery setting, these results suggest that food availability may not be the sole driver behind the observed reduced growth differences found between farmed and wild fishes under natural conditions

Recapturing escaped fish from marine aquaculture is largely unsuccessful: alternatives to reduce the number of escapees in the wild

Farmed fish that escape and mix with wild fish populations can have significant ecological and genetic consequences. To reduce the number of escaped fish in the wild, recapture is often attempted. Here, we review the behaviours of escapees post‐escape, and how recapture success varies with escaped fish size, the size of the initial escape event and recapture methods. Success rates of fishing gears varied among species, with gill‐nets and coastal barrier nets most effective for recapture of salmonids. Recapture success was strongly negatively correlated with both fish size and the number of fish escaped, regardless of species. Recapture success was universally low across all studied species (8%). Numerous tracking studies of escaped fish indicate that recapture efforts should be initiated within 24 h of an escape incident for highest recapture success. However, most large escape events are due to storms, which mean recapture efforts rarely start within this timeframe. Recapture of escaped fish is broadly ineffective in marine habitats, with rare exception. High bycatch rates during ineffective recapture attempts imply that large‐scale recapture efforts should be weighed against the possibility of affecting wild fish populations negatively. We suggest three alternative approaches to reduce escapee numbers in wild habitats: (i) protect populations of predatory fish around sea‐cage farms from fishing, as they prey upon smaller escapees; (ii) construct impact offset programmes to target recapture in habitats where escapees can be efficiently caught; and (iii) ensure technical standards are legislated so that fish farmers invest in preventative technologies to minimize escapes