Biomedicine is often presented as the driving force behind improvements in cancer care, with genomics the latest innovation poised to change the meaning, diagnosis, treatment, prevention and lived experience of cancer. Reviewing sociological analyses of a diversity of patient and practitioner experiences and accounts of cancer during the last decade (2007–17), we explore the experiences of, approaches to and understandings of cancer in this period. We identify three key areas of focus: (i) cancer patient experiences and identities; (ii) cancer risk and responsibilities and (iii) bioclinical collectives. We explore these sociological studies of societal and biomedical developments and how sociologists have sought to influence developments in cancer identities, care and research. We end by suggesting that we extend our understanding of innovations in the fields of cancer research to take better account of these wider social and cultural innovations, together with patients, activists' and sociologists' contributions therein.
BackgroundMultiple myeloma (MM) is a plasma cell tumour with an approximate annual incidence of 4500 in the UK. Therapeutic options for patients with MM have changed in the last decade with the arrival of proteasome inhibitors and immunomodulatory drugs. Despite these options, almost all patients will relapse post first-line autologous stem cell transplantation (ASCT). First relapse management (second-line treatment) has evolved in recent years with an expanding portfolio of novel agents, driving response rates influencing the durability of response. A second ASCT, as part of relapsed disease management (salvage ASCT), has been shown to prolong the progression-free survival and overall survival following a proteasome inhibitor-containing re-induction regimen, in the Cancer Research UK-funded National Cancer Research Institute Myeloma X (Intensive) study. It is now recommended that salvage ASCT be considered for suitable patients by the International Myeloma Working Group and the National Institute for Health and Care Excellence NG35 guidance.Methods/designACCoRd (Myeloma XII) is a UK-nationwide, individually randomised, multi-centre, multiple randomisation, open-label phase III trial with an initial single intervention registration phase aimed at relapsing MM patients who have received ASCT in first-line treatment. We will register 406 participants into the trial to allow 284 and 248 participants to be randomised at the first and second randomisations, respectively.All participants will receive re-induction therapy until maximal response (four to six cycles of ixazomib, thalidomide and dexamethasone). Participants who achieve at least stable disease will be randomised (1:1) to receive either ASCTCon, using high-dose melphalan, or ASCTAug, using high-dose melphalan with ixazomib. All participants achieving or maintaining a minimal response or better, following salvage ASCT, will undergo a second randomisation (1:1) to consolidation and maintenance or observation. Participants randomised to consolidation and maintenance will receive consolidation with two cycles of ixazomib, thalidomide and dexamethasone, and maintenance with ixazomib until disease progression.DiscussionThe question of how best to maximise the durability of response to salvage ASCT warrants clinical investigation. Given the expanding scope of oral therapeutic agents, patient engagement with long-term maintenance strategies is a real opportunity. This study will provide evidence to better define post-relapse treatment in MM.Trial registrationISRCTN, ISRCTN10038996. Registered on 15 December 2016.Electronic supplementary materialThe online version of this article (10.1186/s13063-018-2524-8) contains supplementary material, which is available to authorized users.
Background: The depth of response both pre- and post- autologous stem cell transplant (ASCT) has been shown to correlate with clinical outcome for myeloma patients. Maximizing response can be achieved by modifying therapy either at induction, transplant, consolidation or during maintenance. In this work we explore the role of pre-transplant induction therapy in the UK NCRI Myeloma XI clinical trial and whether the number of cycles of induction impacts on clinical outcome. Methods: Myeloma XI recruited 2568 newly diagnosed transplant eligible patients. Patients were initially randomized between immunomodulatory agent containing triplets comprising cyclophosphamide, dexamethasone and either lenalidomide or thalidomide (CRD vs CTD). Patients were treated to maximum response and for a minimum of four cycles of therapy. At maximum response, patients with a VGPR or CR proceeded straight to ASCT, whilst those with a suboptimal response (PR/MR) entered a second randomization between a bortezomib containing triplet (CVD) or no further therapy, and those with refractory disease (SD/PD) all received CVD. The protocol was amended subsequently to compare the upfront quadruplet KCRD to the response adapted approach. After ASCT patients were randomized between maintenance therapy with lenalidomide +/- vorinostat or no further therapy. In this exploratory analysis we compared baseline characteristics and outcomes for patients who received 4 cycles of initial induction (the protocol defined minimum), 5-6 cycles or >6 cycles. Patients who received <4 cycles were excluded. Results In total 787 patients completed 4 cycles of initial induction, 1223 had 5-6 cycles and 281 had >6 cycles. A comparison of baseline characteristics showed that the group receiving more induction therapy was associated with a higher ISS stage and greater disease burden at baseline. The percentage of patients with ISS stage II/III was greater in those receiving more cycles of therapy, 4 cycles 57.6%, 5-6 cycles 62.2%, >6 cycles 67.3%. The percentage bone marrow infiltration increased (BM plasma cells >20% was 32.3%, 42.3% and 43.4% respectively). Patients with an IgG paraprotein made up a larger proportion of those receiving more cycles 50.2%, 65.1% and 67.3% respectively, whereas those with IgA or light chain disease showed the opposite pattern. Age, sex and performance status showed no association. Cytogenetic risk was equally distributed across groups with a subset of standard risk patients requiring additional cycles of therapy, indicating some slow responders even in this good prognosis group. KCRD had a superior time to and depth of response; patients receiving KCRD required a median of only 4 cycles and had a much higher proportion of patients receiving only 4 cycles (KCRD 49.8%, CRD 29.7%, CTD 21.7%). Response at the end of 4 cycles of therapy and at the end of initial induction, Figure 1, shows that additional cycles deepened response. This was consistent across all induction regimens. Patients receiving >4 cycles of therapy, however, never attained as deep responses as those whose maximum response was achieved by 4 cycles and were therefore also more likely to receive subsequent therapy with CVD intensification in the response adapted arm of the study. Overall, the depth of response at the end of initial induction was associated with a significant effect on PFS (Median PFS: CR 63.3 months, VGPR 43.8 months, PR 30.6 months, p<0.0001) with a trend toward the same effect on OS. There was no statistically significant difference in progression-free or overall survival for patients receiving 4, 5-6 or >6 cycles of initial induction. Conclusions: The results suggest that continuing induction to maximum response is not detrimental to patient outcome and may have overcome an adverse impact of a less deep response. Continuing induction therapy until maximum response may improve outcomes for patients with an otherwise suboptimal response at the end of 4 cycles. Disclosures Pawlyn: Amgen: Consultancy, Honoraria, Other: Travel Support; Janssen: Honoraria, Other: Travel support; Celgene Corporation: Consultancy, Honoraria, Other: Travel support; Takeda Oncology: Consultancy, Other: Travel support. Jackson:Merck Sharp and Dohme: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel Support, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding, Speakers Bureau. Cairns:Merck Sharp and Dohme: Research Funding; Amgen: Research Funding; Celgene: Research Funding. Striha:Celgene: Research Funding; Janssen: Research Funding; Amgen: Research Funding; Abbvie: Research Funding; MSD: Research Funding. Hockaday:MSD: Research Funding; Janssen: Research Funding; Amgen: Research Funding; Millenium: Research Funding; Celgene: Research Funding; Abbvie: Research Funding. Jones:Celgene: Honoraria, Other: Travel support, Research Funding. Boyd:Celgene: Consultancy, Honoraria, Other: Advisory role; Janssen: Honoraria, Other: Travel and Accommodation expenses; Novartis: Consultancy, Honoraria. Kishore:Celgene: Honoraria; Takeda: Honoraria, Other: travel support. Garg:Takeda: Other: Travel Grant; Amgen: Honoraria, Other: Travel Support; Novartis: Other: travel support, Research Funding; Janssen: Honoraria. Williams:Celgene: Honoraria, Other: travel support, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Takeda: Honoraria, Other: travel support, Speakers Bureau; Novartis: Honoraria; Janssen: Honoraria, Other: travel support, Speakers Bureau. Karunanithi:Celgene: Other: Travel support, Research Funding; Janssen: Other: Travel support, Research Funding. Lindsay:Janssen: Consultancy; Novartis: Other: Travel support; Celgene: Honoraria, Other: Travel support; BMS: Consultancy, Other: Travel support; Takeda: Other: Travel support. Jenner:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cook:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Russell:Jazz Pharma: Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau; Daiichi Sankyo: Consultancy. Kaiser:Bristol-Myers Squibb: Consultancy, Other: travel support; Chugai: Consultancy; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Other: travel support; Celgene: Consultancy, Honoraria, Research Funding. Drayson:Abingdon Health: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Owen:Janssen: Consultancy, Other: Travel support; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Other: Travel Support. Gregory:Celgene: Consultancy, Honoraria, Research Funding; Merck Sharp and Dohme: Research Funding; Janssen: Honoraria; Amgen: Research Funding. Morgan:Takeda: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Davies:Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.
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