A universal basic income in the superstar (digital) economy

This paper argues that the structural logic of the digital economy is to widen inequality, not only through its increasing automation of jobs but also in its efficiency in delivering ever greater profits to a smaller number of already-enriched organisations and individuals. Remedial actions that might be taken to mitigate the effects of some of the digital economy’s structural flaws are interrogated here, with a particular focus on universal basic income (UBI) and stake-holding schemes. The paper considers whether the digital economy’s inherent problems are of such magnitude that some sort of financial support for workers to buttress long periods of idleness, or to enable them to take risks in increasingly volatile and unstable global markets, is both desirable and politically feasible

Baseline characteristics of patients in the reduction of events with darbepoetin alfa in heart failure trial (RED-HF)

<p>Aims: This report describes the baseline characteristics of patients in the Reduction of Events with Darbepoetin alfa in Heart Failure trial (RED-HF) which is testing the hypothesis that anaemia correction with darbepoetin alfa will reduce the composite endpoint of death from any cause or hospital admission for worsening heart failure, and improve other outcomes.</p> <p>Methods and results: Key demographic, clinical, and laboratory findings, along with baseline treatment, are reported and compared with those of patients in other recent clinical trials in heart failure. Compared with other recent trials, RED-HF enrolled more elderly [mean age 70 (SD 11.4) years], female (41%), and black (9%) patients. RED-HF patients more often had diabetes (46%) and renal impairment (72% had an estimated glomerular filtration rate <60 mL/min/1.73 m2). Patients in RED-HF had heart failure of longer duration [5.3 (5.4) years], worse NYHA class (35% II, 63% III, and 2% IV), and more signs of congestion. Mean EF was 30% (6.8%). RED-HF patients were well treated at randomization, and pharmacological therapy at baseline was broadly similar to that of other recent trials, taking account of study-specific inclusion/exclusion criteria. Median (interquartile range) haemoglobin at baseline was 112 (106–117) g/L.</p> <p>Conclusion: The anaemic patients enrolled in RED-HF were older, moderately to markedly symptomatic, and had extensive co-morbidity.</p&gt

Dose-Intensive (R-HCVAD) and High Dose Therapy (ASCT) Frontline Strategies More Than Double PFS Over Standard Therapy in MCL Patients

Abstract Abstract 3658 Background: While current front-line treatment options for the management of MCL are still debated, a growing consensus in the lymphoma community suggest that MCL pts show superior outcomes with either consolidative ASCT or dose-intensive treatment approaches over CHOP-like regimens and that cytarabine containing regimens achieve earlier and deeper (hence more durable) responses. On the other hand, such dose-intensive strategies can be difficult to administer to the elderly (a relevant issue with a median age at diagnosis of mid 60's) or in pts with comorbidities. Few studies have looked at the comparative effectiveness of initial therapies in MCL in the community setting. Methods: Utilizing KM and Cox regression analyses, we performed a single-center, retrospective cohort analysis to describe the survival experience of 139 MCL pts (med follow up 50 months) treated in the front-line setting with R-CHOP (n=35), R-HCVAD (n=63) or induction-chemotherapy followed by HDT-ASCT (n=41). The primary endpoints of this retrospective cohort analysis were overall (OS) and progression free survival (PFS). The proportional hazards assumption was met for this analysis. Results: The JTCC MCL outcomes database contains 214 total patient entries (newly dx + relapsed MCL) from 1993–2012 of which 139 pts met inclusion/exclusion criteria with complete outcomes data available. The R-CHOP, R-HCVAD and HDT-ASCT groups were comparable in terms of known prognostic factors including age (median 60), ECOG PS (median 1), MIPI score (median score 4, 30% int risk, 29% high risk) and Ki-67 (median 30% and range 5–95%). The median PFS was superior for pts treated with either R-HCVAD (53 months) or ASCT (63 months) (p=&lt;.001, LR test, Figure) compared to R-CHOP (24 months). No significant difference (HR 1.15, p=.7, 95%CI .5–2.5) in PFS could be detected between pts age &lt; 65 vs. those age &gt;= 65 (n=25) treated with either R-HCVAD (med PFS 46 months) or HDT-ASCT (med PFS 54 months). Median OS favored pts treated with R-HCVAD or HDT-ASCT (103 months and 108 months respectively) over R-CHOP (67 months) but did not meet statistical significance (p=.16, LR test). Conclusions: These data represent the largest published single center experience of MCL patients treated in the front-line setting. Our results confirm a recent NCCN report showing benefit of dose-intensive/high dose strategies in MCL over conventional therapy with more than doubling median PFS over R-CHOP. Of notice when compared to recently updated STiL trial (Rummel ASCO 2012, abst #3) our results are c/w with a median PFS of 22 months after R-CHOP but appear superior to med PFS (35 months) seen with bendamustine-rituximab in MCL even in a subset of elderly pts &gt;= age 65. Our results support the use of dose-intensive strategies in a fit geriatric patient population. Finally the excellent PFS seen in that setting represents a promising platform for integrating novel agents in combination and/or maintenance in future strategies to prevent recurrence and continue to improve MLC pts outcome. Disclosures: Mato: Genentech: Speakers Bureau; Seattle Genetics: Speakers Bureau; Millennium: Speakers Bureau; Celgene: Speakers Bureau. Feldman:Allos: Speakers Bureau; celgene: Speakers Bureau; Seattle Genetics: Speakers Bureau; Merck: Speakers Bureau. Goy:Milennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; J &amp; J: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. </jats:sec

Dose Intensive Induction Followed By Allogeneic Stem Cell Transplantation More Than Doubles Progression-Free and Overall Survival In “Double-Hit” Lymphoma (DHL)

Abstract Introduction There is a growing awareness of the molecular heterogeneity of DLBCL beyond the GC and non-GC well established subtypes. “Double-hit” lymphoma (DHL) harboring rearrangements of c-Myc and BCL2 have been clearly associated with a poor prognosis. It is well recognized that these pts do poorly with R-CHOP and typically cannot be salvaged using ASCT in the relapse setting. Small series suggest that dose-intensive (DI) strategies may lead to better outcomes in the frontline setting and that some pts achieve durable disease control after allogeneic SCT in the relapse setting. We report here one of the largest series of consecutive DHL pts treated with a DI approach followed by allogeneic SCT and compare outcomes to a similar pt population treated with standard dose (SD) chemotherapy. Methods We conducted a retrospective cohort study of DHL pts to evaluate clinical outcomes stratified by chemotherapy intensity ± SCT treated at John Theurer Cancer Center (JTCC) between 4/09-6/13. DHL was defined by the presence of c-Myc rearrangement (FISH) in combination with rearrangement of BCL2 (FISH) or BCL2 over expression (IHC). Primary study endpoints were PFS and OS assessed by chart review and SSDI database. Investigators were blinded to clinical outcomes. A group of hematopathologists reviewed all cases to verify DHL status (also blinded to outcome). Statistical tests included a two-sample t-test to compare baseline characteristics between groups and Kaplan-Meier and Cox regression survival analyses (med follow up 7.9 months, max follow up 46 months). Results Among the 280 pts with either DLBCL or FL treated between 4/09-6/13 at JTCC, 37 pts (12%) were identified as DHL [100% c-Myc + rearrangement by FISH; 86% t(14;18) + rearrangement by FISH and 95% BCL2 over expression by IHC]. These included 68% de novo DHL: 68% DLBCL, 24% FL, 8% transformed FL and 82% were of germinal center cell origin (Hans). Baseline pt characteristics included med age 60 yr (range 23-84), 57% males, 60% aaIPI ≥3, 93% stage III-IV, 29% BM involvement, 76% bulky disease, 61% extra-nodal disease, med LDH 899 (range 419-8276) and med Ki-67 was 85% (range 20-99%). Treatment regimens included a DI regimen in 66% (n=24) [R-hyper-CVAD, R-CODOX-M/IVAC (Magrath Regimen), DA-R-EPOCH] or a SD regimen in 33% (n=12) [mostly R-CHOP, R-EPOCH (not DA), R-ESHAP]. Of the DI group, 42% of pts underwent SCT as consolidation (73% allogeneic, 27% autologous). Allogeneic SCT included: 25% URD, 75% myeloablative conditioning (Flu/Mel, Cy/TBI, BEAM). There were no significant differences between DI vs. SD groups in terms of pt age, stage, LDH, cell of origin, number of cycles of chemotherapy or Ki-67 (p=NS). Med PFS for the entire cohort was 30.2 months. When stratified by chemotherapy intensity, there was a significant difference in PFS for the DI vs. SD treatment group [46 vs. 8 months, HR 0.26, p=0.005]. The added benefit of SCT was demonstrated when pts were stratified by transplantation status (Figure 1): med PFS for DI with SCT, DI without SCT, and SD were 46, 14.8 and 4.9 months, respectively [DI with SCT vs. SD, HR 0.079, p=0.016; DI without HSCT vs. SD, HR 0.53, p=0.237]. Med OS for SD group was 11.1 months, while med OS for the DI ± SCT groups has not been reached (Figure 2) [DI with SCT vs. SD, HR 0.13, p=0.05; DI without HSCT vs. SD, HR 0.73, p=0.6]. Conclusions As previously recognized, DHL do very poorly with SD alone. DI strategies with allogeneic SCT lead to significantly longer PFS and OS. Though our series is a retrospective analysis and numbers remain small, this is a relatively large series of “true DHL” (with 100% c-Myc rearrangement by FISH and 86% t(14;18) translocation), a situation where no treatment has demonstrated long term benefit. The effect of DLI (a few relapses post-SCT converted to CR after DLI) and the durability of PFS support a GVL effect of allogeneic SCT in DHL. Prospective screening for DHL is warranted in high risk B-cell NHL particularly based on high Ki-67. Additional studies are needed to confirm the benefit of allogeneic SCT consolidation after DI induction therapy. Disclosures: No relevant conflicts of interest to declare. </jats:sec

Allogenic Transplantation in Lymphomas: A Focused Analysis On Aggressive Lymphomas and Factors Predictive of Outcome in a Series of 179 Pts Treated At John Theurer Cancer Center.

Abstract Abstract 3120 Introduction: Chemo-immunotherapy (i.e. rituximab combinations) has clearly had a significant impact on the outcome of all B-cell NHL both in terms of PFS and OS. However in the relapse/refractory setting a large proportion of pts still do very poorly especially in aggressive subtypes including DLBCL and MCL. Salvage therapy followed by HDT-ASCT in relapsed DLBCL remains the standard, though pts with early failures (&lt;1y) and/or prior exposure to rituximab still show dismal results (CORAL data). In MCL the use of HDT-ASCT in the relapse setting is debated given the frequency of chemo-resistance leading to poor results even in second CR. The use of allogeneic transplantation was developed based on observations c/w with a clear GVL effect in NHL as illustrated by pts going into remission after DLI injections. The development of non-myeloablative approaches has allowed expansion of use of allogeneic BMT in relapsed/refractory NHL. We report here one of the largest series (179 consecutive pts) with relapsed/refractory lymphoma focusing on overall survival and outcome predictors. Methods: Utilizing Kaplan-Meier survival and Cox regression methods, we report on the outcome of 179 consecutive pts with relapsed/refractory lymphoma who underwent allogeneic stem cell transplantation at the John Theurer Cancer Center between 1995–2012. The primary study endpoint was overall survival (OS) assessed by chart and SSDI database review. Secondary study endpoints included examination of the association between overall survival and allogeneic stem cell source, donor source, development of GVHD, pre-transplant chemo-sensitivity and prior failure to HDT-ASCT (second transplant). The proportional hazards assumption was met for this analysis. Results: Survival data on 179 pts (median age 48, range 20–71) were analyzed, representing 86 deaths and 5720 total months at risk (median follow up=12.3 months). Baseline characteristics included: ECOG PS (med 1, range 0–2), diagnosis (25% DLBCL, 21% HD, 20% MCL, 13% FCL, 13% PTCL, 8% other), donor source (50% matched SIB, 31% MUD, 19% mismatched MUD), stem cell source (73% PB, 23% BM, 6% Cord) and prior autologous SCT (38%). The median OS for the entire cohort was 31.2 months. OS KM curves by selected aggressive NHL subtypes are represented in Figure 1. We performed COX regression analyses to address outlined secondary endpoints. In univariate analyses statistically significant inferior outcomes were associated with the use of mismatched unrelated donor (HR 1.4, p=.01, Figure 2), bone marrow donor stem cells vs. PBSCT (HR=1.7 p=.04), pre-transplant stable/refractory disease (HR 1.8, p=.03), absence of cGVHD (HR=4.7, p&lt;.001) and presence of acute GVHD (HR 2.8, p=.001). No difference in OS was detected whether pts had undergone allogeneic SCT as a second transplant (med time between auto/allo=20.9 months) following relapse after auto SCT (HR 1.14, CI .75–1.73, p=.5). Conclusions: This series represents a large cohort of poor risk, relapsed/refractory lymphoma pts treated consecutively with allogeneic stem cell transplantation over a &gt; 10-year period at our institution with the following observations: Disclosures: Mato: Celgene: Speakers Bureau; Millennium: Speakers Bureau; Seattle Genetics: Speakers Bureau; Genentech: Speakers Bureau. Goldberg:Eisai: Speakers Bureau. Feldman:Allos: Speakers Bureau; celgene: Speakers Bureau; Seattle Genetics: Speakers Bureau; Merck: Speakers Bureau. Goy:Milennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; J &amp; J: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. </jats:sec

Ricer (Rituximab, Ifosfamide, Carboplatin, Etoposide, Revlimid) Is Well-Tolerated Salvage Regimen in First Relapse/Primary Refractory DLBCL Allowing Consolidation with Autologous Stem Cell Transplant

Abstract Abstract 3710 Background: Relapsed/refractory DLBCL has poor prognosis in the rituximab era. Pts who failed Rituximab-containing initial chemo regimen within 12 mo do particularly poorly. (ORR 46–51% vs. 83–88%, EFS 20% vs. 45% at three years). Novel salvage therapies to overcome chemo resistance and maintain remission in post transplant setting are needed. The immunomodulatory agent lenalidomide has demonstrated direct tumoricidal and antiproliferative effects in lymphoma and clinical activity and safety in multiple phase II studies in aggressive NHL. Methods: We are conducting a phase I/II trial combining lenalidomide with RICE (rituximab, ifosfamide, carboplatin and etoposide) (RICER) as a salvage regimen in first relapse or primary refractory DLBCL. Four dose levels of lenalidomide are being evaluated in Phase I part of the study: 10mg, 15mg, 20mg, and 25mg given for 7 days (days 1–7) together with RICE. After three cycles of RICER patients with chemo sensitive disease proceed to stem cell collection (off 3rdRICE) and consolidation with BEAM followed by autologous SCT (ASCT). Patients who recover from ASCT toxicities within 90 days are started on maintenance with lenalidomide 25mg daily for 21 days every 28 days for 12 months. Results: 13 patients have been enrolled. DLT was not seen at 25 mg (last dose level tested) of lenalidomide during the salvage part of RICER. No unexpected toxicities were observed by adding lenalidomide to RICE. Grade 3 and 4 hematologic toxicities were comparable to RICE alone and resolved appropriately and planned dose density and dose intensity of RICER were preserved. One episode of febrile neutropenia occurred during RICER administration. No new DVT's occurred during lenalidomide administration either in salvage or in post ASCT maintenance part of the trial. Stem cell collection was successful in all but one patient. So far seven patients have completed ASCT and five patients were able to start on maintenance lenalidomide post transplantation. No unusual toxicities were observed in the peritransplantation period and there was no delay in engraftment: median days to ANC of &gt;500 is 11, and to plts over 20K/mL is 11. In the maintenance post ASCT there was no infection but routine dose reductions were required because of myelotoxicity. Conclusions: Disclosures: Feldman: allos: Speakers Bureau; merck: Speakers Bureau; celgene: Speakers Bureau; seattle genetics: Speakers Bureau. Off Label Use: Lenalidomide in combination with chemotherapy as salvage regimen for DLBCL. Mato:Celgene: Speakers Bureau; seattle genetics: Speakers Bureau; genentech: Speakers Bureau; millennium: Speakers Bureau. Goldberg:Eisai: Speakers Bureau. Vesole:Celgene Corp.: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Millennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Siegel:Celgene: Advisory Board Other, Honoraria, Speakers Bureau; Millennium Pharma: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau; Onyx: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau; Merck: Advisory Board, Advisory Board Other, Honoraria, Speakers Bureau. Goy:Milennium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; J &amp; J: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. </jats:sec