Background: Following the PANORAMA-1 trial, Panobinostat was approved in 2016 for the treatment of relapsed/refractory multiple myeloma (RRMM) in combination with bortezomib and dexamethasone (Pan-Bor-Dex) following at least 2 prior regimens including bortezomib and an immunomodulatory imide drug (IMiD). Since then, there have been several new drug approvals for RRMM and the treatment landscape has therefore changed significantly with Pan-Bor-Dex being used at later stages of the disease. It is therefore important to evaluate the efficacy and toxicity of this regimen in a real world setting given that the patient population being treated may be quite different to that in the PANORAMA-1 trial. Furthermore dosing schedules and dose modifications vary considerably in practice and may play an important part in minimising toxicity, preventing drug discontinuation and potentially impacting on duration of response. Aims: The primary objective of this study was to determine the progression free survival (PFS) of RRMM patients in the UK receiving Pan-Bor-Dex. Secondary objectives were to assess overall response rate (ORR), depth of response, time to best response, duration of response, time to next treatment and overall survival as well as to assess incidence of grade ≥3 adverse events (AEs), dose modifications and impact on health care resource utilisation. Methods: This was a UKMRA retrospective, observational, multi-centre study conducted at hospitals across England and Wales. All patients who received at least 1 cycle of Pan-Bor-Dex at each site between 01 Jan 2016 and 01 Jan 2018 were enrolled in the study. 01 Jan 2020 was the data cut-off date and patients who had not progressed by this date were censored at this timepoint. Results: 219 patients were enrolled across 26 University and district general hospitals. The median age of the cohort was 69yrs (IQR 60-75) with 56% (n=106) aged ≥70yrs. The median number of prior treatment lines was 4 (IQR 3-5). 22% were refractory to a proteosomal inhibitor, 68% to an ImiD and and 5% to an anti-CD38 antibody. 54% had received an autologous stem cell transplant. Median number of cycles of Pan-Bor-Dex completed was 4 with 7.3% (n=16) of patients achieving the maximum 16 cycles approved by the National Institute of Health and Care Excellence (NICE). ORR was 61% (n=133) with 37% achieving a partial response, 19% (n=44) a very good partial response and 5% (n=7) a complete response. Median PFS was 4.2 months (95% CI, 3.5-6) (see Figure). Initial sub-group analyses showed a significant difference in PFS between age groups. Older patients ≥70yrs achieved a median PFS of 6 months compared to 3.5 months in patients <70yrs (p value 0.02). Toxicity led to discontinuation in 18% (n=38) of patients. Most frequent grade≥3 AEs included thrombocytopenia (59%), anaemia (39%), neutropenia (32%), diarrhoea (12%) and fatigue (12%). Image:Summary/Conclusion: In this UK real world study of RRMM patients from 2016-2018 we have shown that the Pan-Bor-Dex regimen despite being used, on average, as fifth line treatment resulted in an ORR of 61%, comparable to that seen in the PANORAMA-1 Trial where patients were less heavily pre-treated. The overall median PFS was 4.2 months, not dissimilar to other drug regimens in advanced stage myeloma. Further data will be presented at the meeting including results of multivariate analysis to identify baseline patient factors that correlate with PFS.
The process of ageing has an impact on the entire human body including the organ systems. In transplantation, professionals are daily faced with risk assessment of suitable donor offers , whether to accept a liver graft for a specific recipient. In this context, livers from elderly donors are more frequently accepted for transplantation, to increase the donor pool and compensate the high waiting list mortality. In the current practice it is not unusual to accept 60-year old donor livers for transplantation, as the donor demographics have significantly changed over the years. However, controversy exists regarding the use of livers from donors above 70 or 80 years, particular in combination with other risk factors, e.g. liver steatosis, warm ischaemia or long cold storage. This review focuses first on the impact of ageing on liver morphology and function. Second, we will highlight outcome after transplantation from elderly donors. Finally, we describe further risk factors and donor–recipient selection under the scope of old donor organs and include our institutional experience and policy.
This thesis examines the relationship between the production of urban space
and the reproduction of capital. Taking the Queen Elizabeth Olympic Park as a
case study, I conducted ethnographic research during the London 2012
Olympics and the Park's first 'Legacy' year. My research proceeded from an
embodied walking practice (which prompted reflection on my transgender
presentation as a complicating factor), and also included interviews and archival
research. My analysis centres on Henri Lefebvre, situating his work on space
within a concern for the relationship between everyday life and the concrete
abstractions constituted therein. Taking this relationship as essential to the
reproduction of capital, I explore the production of the Olympic Park as an
actually-existing abstract space that mirrors the dual character of the value
form.
I open my account of this production with the Olympic festival, a total social
moment mobilised towards the realisation of value. I then examine each of
Lefebvre's three formants of abstract space in turn. I present the construction of
the Park as the materialisation of an abstractly conceived space designed to
incorporate a disordered post-industrial space into a new mode of
accumulation. I frame the inhabitation of the Park in its Legacy era as a
temporalisation of empty space, arguing that abstract time is co-constituted with
abstract space in internally contradictory everyday practice. And I address the
incorporation of the Park into a set of post-industrial, anti-urban, and leisureoriented
spaces that form a representational space reflective of the movement
of capital in its ascendant, financialised, form. I conclude with a discussion of
the Olympic Park as 'catalyst', securing the reproduction of capital by
encouraging further redevelopment, but also sharpening capital's contradictions
as an abstract space in conflict with its own concrete content, predicated on the
subsumption of the utopian potential of everyday life.
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