P947: Comparative Effectiveness of Oral Ixazomib-Lenalidomide-Dexamethasone (Ird) After Initial Bortezomib (V)-Based Induction vs. Parenteral V-Based Therapy in Newly Diagnosed Multiple Myeloma (Ndmm)

Background: Long-term proteasome inhibitor (PI)-based treatment can improve outcomes for patients (pts) with multiple myeloma (MM). However, prolonged parenteral PI therapy (e.g. with V) can be challenging to achieve in routine clinical practice, and outcomes for pts are often poorer in this setting compared with clinical trials. The phase IV, community-based, single-arm US MM-6 study (NCT03173092) is assessing in-class transition (iCT) from V-based induction to all-oral IRd in transplant ineligible NDMM pts treated in routine clinical practice, with the objective of increasing the duration of PI-based treatment while maintaining quality of life. INSIGHT MM is the largest global, prospective, observational study of MM pts (>4,200), and provided a subset of patients as the comparator cohort. This enabled assessment of iCT vs V-based therapy in NDMM pts in routine clinical practice in the US. Aims: To examine the comparative effectiveness of IRd following initial V-based induction (3 cycles; US MM-6 pts; ‘IRd’ cohort) vs continued V-based therapy (INSIGHT MM pts; ‘V-based’ cohort) in NDMM pts. Methods: A secondary analysis of non-transplant eligible US NDMM pts with ≥stable disease after 3 cycles of V-based induction and baseline Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1 or 2 from the US MM-6 (Manda CLML 2020) and INSIGHT MM (Costello Future Onc 2019) studies was performed. Study outcomes included first-line duration of treatment (DOT), overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and reasons for treatment discontinuation. All analyses were weighted using the inverse probability of treatment weighting (IPTW) approach to reduce the imbalance of potential confounding factors between the two cohorts (adjusted analyses). Kaplan–Meier methods were used to examine DOT, PFS, OS, and associated 95% confidence intervals (CIs); the log-rank test was used to compare distribution of time to events. The Clopper-Pearson method was applied to estimate 95% CIs for ORR. Statistical significance was evaluated at alpha=0.05. Results: 100 pts from the IRd cohort (MM-6) and 111 pts from the V-based cohort (INSIGHT) were included. After IPTW, in the IRd vs V-based cohorts: median age was 75.0 vs 74.8 yrs; 56.7 vs 51.3% of pts were male; 37.4 vs 29.1% had an ECOG PS of ≥2; 48.8 vs 41.4% had International Staging System stage III at initial diagnosis, and 79.5/17.7/2.8 vs 77.3/19.5/3.1% pts had received VRd/ V-cyclophosphamide-d (VCd)/ VRCd as initial induction therapy. Adjusted ORRs in the IRd vs V-based cohorts were 74.1 (95% CI 66.0–82.2) vs 57.5% (95% CI 47.9–67.1; p<0.0001). After a median follow-up of 20.3 and 15.8 months in the IRd and V-based cohorts, respectively, DOT was 10.8 (95% CI 6.5–24.4) vs 5.3 months (95% CI 4.3–7.0; p<0.0001) (see Figure). Median PFS was not estimable (NE) in either cohort; 24-month PFS rates were 85.7 (95% CI 68.1–94.0; IRd cohort) vs 76.5% (95% CI 62.6–85.8; V-based cohort). Median OS was NE in either cohort; 24-month OS rates were 94.0 (95% CI 77.7–98.5; IRd cohort) vs 84.9% (95% CI 70.6–92.6; V-based cohort). In the IRd and V-based cohorts, 16.8 and 16.9% of pts discontinued IRd and V, respectively, due to an adverse event. Summary/Conclusion: US MM-6 NDMM pts who transitioned to IRd after 3 initial cycles of V-based induction had a significantly higher ORR and longer DOT compared with pts who received continued V-based therapy in INSIGHT MM. The results suggest that iCT from continued V-based therapy to all-oral IRd may improve outcomes in pts treated at community oncology clinics

A piscicultura e o ambiente: o uso de alimentos ambientalmente corretos em piscicultura Fish farming and the environment: the use of environmental friendly feeds in fish culture

Embora a ciência da nutrição de peixes esteja longe de estabelecer um padrão geral de exigências nutricionais, a necessidade de desenvolvimento de alimentos de baixo impacto poluente há muito faz parte da agenda das comunidades científica e empresarial internacional da aqüicultura. Não só é absolutamente possível formular alimentos ambientalmente corretos, como é necessário modelar a formulação destes alimentos. Porém, é necessária absoluta acurácia para atender formulações espécie-específicas, considerando-se as interações da biologia e fisiologia nutricional das espécies com os alimentos e com as variações abióticas do meio. O conhecimento disponível sobre as mais de 200 espécies de peixe produzidas comercialmente no mundo é ainda incipiente e os sistemas de produção de peixe, nos diferentes regimes de exploração, estão implantados em todas as condições ecológicas possíveis. Neste cenário, produzir rações ambientalmente corretas é, senão impossível, pelo menos muito difícil e depende da ação coordenada e positiva de produtores, indústria da alimentação, agências regulatórias, e instituições de ensino e pesquisa para definir os parâmetros necessários à consecução deste objetivo.<br>Although fish nutrition science is far from establishing general standards of nutritional requirements, the need for developing low impact feeds has long been included in the agenda of aquaculture's international scientific and business communities of. Not only is absolutely possible to formulate environmental friendly feeds, as it is necessary modeling the formulation of these feeds. However, it is necessary higher accuracy to develop species-specific formulations, considering interactions of the biology and nutritional physiology of the species with the feedstuffs and variations of abiotic environment. The knowledge on more than 200 species of commercially farmed fish is still incipient and fish production systems, in their most varied farming conditions, are set up in every possible ecological conditions. In this scenario, producing environmental friendly feeds is if not impossible, at least very, very difficult, depending on coordinated and positive action of producers, industry, regulatory agencies, and institutions of higher education and research to define the parameters needed to achieve this goal