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In: The Lancet Haematology, Elsevier BV, Vol. 6, No. 12 ( 2019-12), p. e616-e629

Type of Medium: Online Resource

ISSN: 2352-3026

URL: Article

DOI: 10.1016/S2352-3026(19)30167-X

Language: English

Publisher: Elsevier BV

Publication Date: 2019

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 1143-1143

Abstract: Background Lenalidomide is an effective treatment for myeloma and has been studied in a range of combination regimens worldwide. The results of these studies have suggested that prolonged exposure to lenalidomide is important to improve outcomes both as a maintenance agent post-transplant (Attal M et al NEJM 2012, McCarthy et al NEJM 2012) and in the transplant ineligible population (Palumbo A et al NEJM 2012, Benboubker L et al NEJM 2014). In the Myeloma XI study, the largest of its kind, we explored the use of oral lenalidomide continued to disease progression compared to no therapy in both newly diagnosed transplant eligible (TE) and transplant non-eligible (TNE) populations. Here we present the results of this maintenance randomization, which demonstrate the efficacy and safety of maintenance lenalidomide. Methods The Myeloma XI study is a Phase III, UK-based, multicenter, open-label, parallel group, randomized controlled trial for newly diagnosed symptomatic myeloma patients of all ages and includes a maintenance comparison of lenalidomide versus no maintenance. Newly diagnosed symptomatic myeloma patients both TE and TNE were enrolled to the study. Induction treatment in both pathways was with thalidomide or lenalidomide plus cyclophosphamide and dexamethasone, with appropriate dose reductions for TNE patients. TE patients proceded to a standard melphalan 200mg/m2 transplant. Patients were randomized to either maintenance lenalidomide or observation after achieving maximum response (TNE) or at 100 days after transplant (TE). Lenalidomide was administered at a dose of 10mg daily in 21/28 day cycles until disease progression. Dose adjustments for renal impairment and following AEs were permitted. The primary endpoints for the maintenance randomization were progression-free (PFS) and overall survival. Secondary endpoints included response, toxicity and PFS2. Time-to-event endpoints were measured from maintenance randomization. This abstract summarizes a preliminary analysis, final data will be presented at the meeting. The median follow up in this analysis is 26 months [IQR 12-41]. Results A total of 1550 patients, 828 TE and 722 TNE, median age 61 and 74 years, respectively, were randomized between lenalidomide (n=857) and no maintenance (n=693). The arms were well-balanced for clinical features and response to induction therapy (e.g. ISS stage III: 27% vs 23%, VGPR/CR: 73% vs 73%). The maintenance randomization has met its primary endpoint demonstrating a 55% reduction in risk of progression or death for lenalidomide compared to no maintenance (HR 0.45 [95%CI 0.39-0.52], median PFS 37 vs 19 months, p 〈 0.0001) This significant improvement was observed in each pathway TE: HR 0.46 [95%CI 0.36-0.58], median PFS 60 vs 28 months, p 〈 0.0001. TNE: HR 0.44 [95%CI 0.36-0.53], median PFS 26 vs 12 months, p 〈 0.0001. The benefit of lenalidomide maintenance on PFS persisted across risk subgroups and was independent of induction therapy and response. An exploratory analysis of 132 patients stopping lenalidomide treatment for reasons other than disease progression (91 toxicity, 28 patient choice and 13 clinician choice) shows that patients receiving greater than 12 months of treatment have an improved median PFS compared to those stopping earlier (HR 0.35 [95%CI 0.18-0.68], 49 vs 31 months, p 〈 0.0015). At this time 445 patients continue to receive lenalidomide maintenance on study. Of patients who have stopped therapy, only 21.5% did so due to toxicity. Relevant grade 3/4 adverse events were: neutropenia 35%, thrombocytopenia 7.4%, anaemia 4.4%, peripheral neuropathy 1.4%. Venous thromboembolism occurred in 2.3%. Second primary malignancy (SPM) data was collected and the relationship with maintenance therapy reviewed. 72 SPM were observed (24 no maintenance, 48 lenalidomide). Haematologic malignancy crude incidence was 0.3% vs. 0.9%. While we found a slight excess of SPM in older patients these were mostly non-invasive and did not impact the outcome benefit demonstrated. Conclusion The use of maintenance lenalidomide treatment results in highly significant improvements in PFS for patients of all ages and should be standard of care. On behalf of the NCRI Haem-Onc CSG Disclosures Jackson: Amgen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau. Davies:Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Pawlyn:Takeda Oncology: Consultancy; Celgene: Consultancy, Honoraria, Other: Travel Support. Jones:Celgene: Honoraria, Research Funding. Kishore:celgene: Other: travel grant. Garg:Janssen: Other: Travel support, Research Funding, Speakers Bureau; Takeda: Other: Travel support; Novartis: Other: Travel support, Research Funding. Williams:Takeda: Honoraria, Other: Travel support, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Novartis: Honoraria; Janssen: Honoraria, Other: Travel support, Speakers Bureau; Celgene: 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; Takeda: Other: Travel support; BMS: Consultancy, Other: Travel support; Celgene: Honoraria, Other: Travel support. Jenner:Janssen: Consultancy, Honoraria, Other: Travel support, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel support; Amgen: Consultancy, Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria. Cook:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau. Kaiser:BMS: Consultancy, Other: Travel Support; Takeda: Consultancy, Other: Travel Support; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Chugai: Consultancy. Drayson:Abingdon Health: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Owen:Takeda: Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Other: Travel support. Morgan:Takeda: Consultancy, Honoraria; Bristol Meyers: Consultancy, Honoraria; Janssen: Research Funding; Univ of AR for Medical Sciences: Employment; Celgene: Consultancy, Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.1143.1143

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 245-245

Abstract: Introduction. Minimal residual disease (MRD) is a powerful predictor of outcome in multiple myeloma (MM). We have previously demonstrated, in transplant eligible patients, that the level of MRD as a continuous variable independently predicts both PFS and OS, with approximately a one year median OS benefit per log depletion (J Clin Oncol 2013; 31:2540-7 and Blood 2015; 125:1932-5). The impact of MRD also appears to be independent of therapy received. There is more limited data on the applicability of MRD assessment in transplant ineligible patients, largely as a consequence of low rates of CR historically within this patient cohort. Patients and Methods. In this analysis we have assessed the impact of MRD on PFS amongst patients treated within the non-intensive arm of the NCRI Myeloma XI trial. Patients were randomised between thalidomide (CTDa) and lenalidomide (RCDa) based induction therapies with responding patients being subsequently randomised to maintenance with lenalidomide monotherapy, or no further therapy. Bone marrow aspirates were obtained at the end of induction and this analysis represents a subset of 297 patients (median age 74 years). MRD was assessed using flow cytometry (sensitivity 10-4) with a minimum of 500,000 cells evaluated with six-colour antibody combinations including CD138/CD38/CD45/CD19 with CD56/CD27 in all cases and CD81/CD117 in additional cases as required. Results. Overall MRD-negativity was demonstrated in 41/297 (13.8%). When considered according to induction therapy received 25/154 (16.0%) of patients randomized to RCDa were MRD-negative compared to 16/143 (10.8%) of those randomized to CTDa (p=0.24; Fisher's exact test). MRD-negativity was associated with a significant outcome advantage as the median PFS was 34 months versus 18 months for MRD-positive patients (p 〈 0.0001, HR 0.44 [95% confidence interval (CI 0.29-0.67)]). This effect was noted in both RCDa (median PFS 17m v 32m; p=0.001, HR 0.41 [95%CI 0.23-0.69] ) and CTDa (median PFS 19m v 34m; p=0.03, HR 0.49 [95%CI 0.26-0.95]). When the impact of MRD was assessed according to induction regimen the outcome of MRD-negative and MRD-positive patients was similar with both regimens (see figure). The impact of MRD was also assessed as a continuous variable across 5 logs of residual disease. Sequential improvements in outcome with each log reduction were demonstrable. Median PFS for the following disease levels; 〈 0.01%, 0.01 - 〈 0.1%, 0.1% - 〈 1%, 1% - 〈 10% and 〉 /=10% were 34, 26, 16, 14 and 9 months respectively (p 〈 0.0001). This pattern was demonstrable in both RCDa and CTDa treated patients (p 〈 0.0001 for both). Multivariate analysis confirmed the independent predictive value of MRD both as a qualitative and continuous quantitative variable (p 〈 0.0001 for both). In both instances achieving an immunofixation-negative CR was not a significant prognostic variable when included in the model with MRD. Conclusions. We would conclude that MRD is a powerful predictor of outcome in transplant ineligible patients and is a meaningful therapeutic goal in this patient group. In contrast to conventional CR it retains independent prognostic significance both as a quantitative and qualitative variable. This data further supports the role of MRD as a primary endpoint and surrogate marker for survival in future clinical trials. Figure. Figure. Disclosures Rawstron: Janssen: Research Funding; BD Biosciences: Other: Remuneration; Gilead: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Honoraria; Genzyme: Honoraria; AbbVie: Honoraria; Roche: Honoraria; Celegene: Honoraria. Pawlyn:Celgene: Consultancy, Honoraria, Other: Travel Support; Takeda Oncology: Consultancy. Davies:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Kaiser:Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Takeda: Consultancy; Bristol-Myers Squibb: Consultancy, Other: Travel support; Chugai: Consultancy. Jones:Celgene: Honoraria, Research Funding. Cook:Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Jenner:Janssen: Consultancy, Honoraria, Other: Travel support, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Other: Travel support; Takeda: Consultancy, Honoraria, Other: Travel support. Drayson:Abingdon Health: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Jackson:MSD: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau. Morgan:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Bristol Meyers: Consultancy, Honoraria; Janssen: Research Funding; Univ of AR for Medical Sciences: Employment. Owen:Celgene: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Other: Travel support; Janssen: Consultancy, Other: Travel support.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.245.245

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 1847-1847

Abstract: Background Lenalidomide (len) has been linked to an increased risk of second primary malignancy (SPM) and in-particular acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS). Haematological SPM (hSPM) incidence in patients receiving len is highest in those also exposed to oral melphalan, resulting in an apparent hSPM incidence of between 3.0-11.4% at 5 years. More recently, meta-analysis has suggested that when used in combination with other agents e.g. cyclophosphamide there is no increased rate of hSPM. Here we report SPM rates in Myeloma XI, the largest randomised trial to date in-which len is used as an induction and maintenance therapy. Methods Myeloma XI is a phase III, randomised, multi-centre, parallel group design, open-label trial comparing thalidomide (thal), len and bortezomib combinations and len as maintenance treatment in NDMM patients. The trial includes transplant eligible (TE) and transplant non-eligible (TNE) pathways. TE patients received high dose melphalan supported by autologous stem cell transplantation if they achieved a very good partial response or better. Patients in both pathways were randomised to maintenance with len (+/- vorinostat) or active observation. Since May 2010, 2745 patients have been recruited with over 1170 patients enrolled for more than 2 years. A total of 1367 patients have entered maintenance with 836 randomised to len (median 6 cycles (range 1-42)). Results Following central committee review of 87 reported SPMs in 84 patients, 69 cases in 67 patients were confirmed (incidence rate (IR) 2.45%). The median time to SPM development from induction is 15.6 months (range 1.2 - 42.5). The cumulative incidence of all SPMs is 0.65% (95% CI 0.35, 0.97), 1.84% (1.26, 2.41) and 3.41% (2.49, 4.43) at one, two and three years respectively, Figure 1. Of SPM patients, 44 (65.7%) were treated on the TNE pathway (IR 3.6%) and 23 (34.3%) on the TE pathway (IR 1.5%). The average age at the time of SPM was 75.1 and 65.9 for the TNE and TE pathways respectively. Thirty seven (56%) patients received len induction with a median time to SPM development of 11.7 months (1.2 - 25.3) in the TE group (n=15) and 18.2 months (3.4 - 30.8) in the TNE group (n=22). The remaining 30 patients (44%) received thal induction with a median time to SPM development in the TE group (n=8) of 31.3 months (6 - 43.1) and 12.6 months (3.4 - 38.4) in the TNE group (n=22). Of the patients who developed an SPM 40 (59.7%) did so following maintenance randomisation. The incidence was highest in those receiving len based maintenance (n=34, IR 4.2%). In the observation arm 6 patients developed an SPM (IR 1.1%). The median time to SPM development from maintenance randomisation is 20.32 months in those receiving len and 15.61 months in the observation only group. 28 of the 40 SPM cases that occurred following maintenance were in the TNE pathway with 24 patients receiving len.The overall incidence of SPM development in TNE patients receiving len maintenance is 7.4%. In the TE patients 12 SPM cases developed following maintenance randomisation with 10 patients receiving len. The overall incidence of SPM in the TE patients treated with len maintenance is 2.0%. Of the remaining patients, 22 (32.9%) developed an SPM during induction and five (7.5%) following induction but prior to maintenance. Eight patients developed a hSPM (IR 0.29%), MDS (n=4), AML (n=2), CML and Hodgkin's Lymphoma. Of these patients four received len induction and seven received len based maintenance. Median time to SPM development for hSPM was 18.2 months (5.9 - 42.5). The remaining 61 SPM cases (59 patients) were solid tumours or non-invasive skin cancers (IR 2.15%). Conclusions The overall incidence rates of SPM are low and an increased rate of hSPM was not seen. The highest SPM incidence was observed in patients receiving len maintenance enrolled to the TNE arm (n=24, IR 7.4%). Advanced age is likely to be a contributing factor but it may be related to treatment duration, which is longer in this group. It is also important to note that 37.5% (n=9) of these cases were non-invasive skin cancers. Committee review of all reported SPMs led to the rejection of 18 cases (20.7%). The commonest reason for rejection was because the malignancy pre-dated trial entry (n=12). We, therefore, recommend incorporating a review process for all trials where SPMs are considered to accurately assess the impact of treatment on SPM development and to prevent the false inflation of SPM figures. Disclosures Jones: Celgene: Other: Travel support, Research Funding. Off Label Use: Lenalidomide and vorinostat as maintenance therapy for myeloma. Pawlyn:Celgene: Honoraria, Other: Travel support; The Institute of Cancer Research: Employment. Kaiser:Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria; BristolMyerSquibb: Consultancy; Chugai: Consultancy; Janssen: Honoraria. Davies:Takeda-Milenium: Honoraria; Onyx-Amgen: Honoraria; University of Arkansas for Medical Sciences: Employment; Celgene: Honoraria. Gregory:Janssen: Honoraria; Celgene: Honoraria. Boyd:Celgene: Honoraria, Other: Travel; Janssen: Honoraria, Other: Travel. Owen:Celgene: Honoraria, Research Funding; Janssen: Honoraria. Jackson:Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Morgan:University of Arkansas for Medical Sciences: Employment; CancerNet: Honoraria; MMRF: Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda-Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Weisman Institute: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.1847.1847

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 189-189

Abstract: Background: Maximising response in myeloma (MM) patients with effective induction regimens prior to autologous stem cell transplant (ASCT) improves progression-free and overall survival. Triplet regimens combining an immunomodulatory agent (IMiD) and/or proteasome inhibitor (PI) are standard of care, however a more personalised approach is achieved by sequential triplet combinations based on an individual's response. Alternatively, quadruplet regimens may be more effective and new generation PIs such as carfilzomib, with less off-target activity, provide the opportunity to investigate this whilst minimising the risk of increased toxicity. The UK NCRI Myeloma XI trial is a large, phase III study aiming to answer these questions in transplant eligible (TE) patients comparing the quadruplet carfilzomib, cyclophosphamide, lenalidomide and dexamethasone to the sequential strategy of triplet IMiD combinations (with thalidomide or lenalidomide) followed by additional PI triplet therapy for those with a suboptimal response ( 〈 VGPR) prior to ASCT. Methods: In 2013, the TE pathway was amended to include KCRD: carfilzomib 36mg/m2 IV d1-2,8-9,15-16 (20mg/m2 #1d1-2), cyclophosphamide (cyclo) 500mg PO d1,8, lenalidomide (len) 25mg PO d1-21, dexamethasone (dex) 40mg PO d1-4,8-9,15-16). Patients are randomised to this up-front quadruplet or the sequential strategy of CRD: cyclo 500mg PO d1,8, len 25mg PO d1-21 PO daily, dex 40mg PO d1-4, 12-15 or CTD: cyclo 500mg PO d1,8,15 thalidomide 100-200mg PO daily, dex 40mg PO d1-4,12-15 given to max. response - patients with VGPR/CR proceed straight to ASCT, PR/MR are randomised to sequential CVD: cyclo 500mg d1,8,15, bortezomib 1.3mg/m2 IV/SC d1,4,8,11, dex 20mg PO d1,2,4,5,8,9,11,12 or nothing and SD/PD all receive sequential CVD. All treatments are given to max. response prior to ASCT, after which there is a maintenance randomisation. Patients: 1512 patients entered the TE pathway prior to amendment (756 CRD, 756 CTD). Of these, 201 patients with a suboptimal initial response went on to receive CVD, 142 following randomisation (initial response PR/MR) and 59 with NC/PD. 788 (of target n=1036) patients have been randomised post-amendment to date (394 KCRD, 197 CRD, 197 CTD). Results: TE patients receiving treatment prior to the amendment had response rates ≥VGPR: CRD 58% vs CTD 52%. For patients receiving the sequential triplet CVD due to a suboptimal response this was upgraded to ≥VGPR in 49% of those with initial MR/PR, 27% with NC/PD. This suggests the overall ≥VGPR rate to this treatment approach prior to ASCT would be approx. 75%. This now needs to be compared to the alternative approach of an upfront quadruplet. Comparing patients contemporaneously randomised to initial induction the patients receiving KCRD have completed a median 4 cycles (range 1-7), CRD 5 (range 1-10) and CTD 6 (range 1-9). Dose modifications have been required in 62% of patients receiving KCRD (56% to carfilzomib, 42% to lenalidomide) 44% CRD (40% to lenalidomide) and 65% CTD (59% to thalidomide). Data for study drug related toxicity in patients who have completed at least one cycle of initial induction are shown in table 1. Serious adverse events suspected to be due to trial medications have occurred in 37% on KCRD, 32% CRD and 35% CTD. Updated toxicity and preliminary response analysis on 23/09/15 will be presented at the meeting. This will include a response comparison at the end of initial induction regimen i.e. KCRD vs CRD vs CTD for an anticipated 700 contemporaneous patients who will have completed treatment. Updated response to the sequencing approach (with 250 patients having received sequential CVD) will also be presented and compared. Conclusions: In our study KCRD, an outpatient delivered 4-drug regimen combining second generation IMiD and PI drugs, is well-tolerated in TE NDMM patients, comparable to 3-drug regimens. Data will be presented at the meeting to compare the response rates achieved with the different regimens and treatment approaches. On behalf of the NCRI Haemato-oncology CSG Table 1. Comparative toxicities KCRD n=261 CRD n=143 CTD n=142 % (no. of patients) Peripheral neuropathy Sensory Gr II-IV 1.9 (5) 1.4 (2) 8.5 (12) Motor Gr II-IV 3.1 (8) 1 (1) 5.6 (8) VTE all grades 4.2 (11) 4.9 (7) 5.6 (8) Anaemia Gr III-IV 9.2 (24) 4.2 (6) 5.6 (8) Neutropenia Gr III-IV 14.9 (39) 16.1 (22) 13.3 (19) Thrombocytopenia Gr III-IV 8.4 (22) 1.4 (2) 1.4 (2) Infusion reaction Gr III-IV 0.4 (1) - - Disclosures Pawlyn: Celgene: Honoraria, Other: Travel support; The Institute of Cancer Research: Employment. Off Label Use: Carfilzomib as induction treatment for myeloma Lenalidomide and vorinostat as maintenance treatments for myeloma. Davies:University of Arkansas for Medical Sciences: Employment; Celgene: Honoraria; Onyx-Amgen: Honoraria; Takeda-Milenium: Honoraria. Jones:Celgene: Other: Travel support, Research Funding. Kaiser:Janssen: Honoraria; Chugai: Consultancy; Amgen: Consultancy, Honoraria; BristolMyerSquibb: Consultancy; Celgene: Consultancy, Honoraria, Research Funding. Jenner:Takeda: Honoraria; Amgen: Honoraria. Cook:Jazz Pharma: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Chugai: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Russell:Therakos: Other: shares. Owen:Celgene: Honoraria, Research Funding; Janssen: Honoraria. Gregory:Janssen: Honoraria; Celgene: Honoraria. Jackson:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Morgan:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda-Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; CancerNet: Honoraria; Weisman Institute: Honoraria; MMRF: Honoraria; MMRF: Honoraria; University of Arkansas for Medical Sciences: Employment; Weisman Institute: Honoraria; CancerNet: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V126.23.189.189

Language: English

Publisher: American Society of Hematology

Publication Date: 2015

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 1144-1144

Abstract: Background Primary refractory myeloma is an important therapeutic challenge; understanding its clinical course and biology is essential if we are to recognize it early and target it therapeutically. Immunomodulatory (IMiD) drugs are widely used as induction therapy with good response rates but a small proportion of patients are refractory. The mechanism underlying IMiD resistance is poorly defined. Mutations in the cereblon pathway are a clear candidate but have not been widely looked for or reported. An important question is whether the primary refractory clone carries class-specific intrinsic resistance biology, leaving it sensitive to other non-cross reactive drugs, or if it is a universal resistance mechanism. We have examined the clinical course of patients with primary IMiD resistance, and whether they respond adequately to subsequent proteasome inhibition (PI), using the results of the largest clinical study in myeloma to date. Methods Myeloma XI is a UK based, open-label, parallel group, randomized controlled trial for newly diagnosed symptomatic myeloma patients of all ages. Treatment was with a combination of cyclophosphamide and dexamethasone plus either lenalidomide or thalidomide (CRD or CTD) for a minimum of 4 cycles (transplant eligible, TE) or 6 cycles (transplant non-eligible, TNE) or to maximum response. Those patients who had not achieved at least a minimal response or who had progressed during induction (PD) subsequently received a PI triplet (cyclophosphamide, bortezomib and dexamethasone, CVD). This abstract summarizes a preliminary analysis of these primary refractory cases, final data will be presented at the meeting. Results The study randomized 3894 patients of all ages giving adequate numbers to identify clinical/biological features in subgroups. Overall 207/3894 (5.3%) of patients had stable disease (SD) or PD at the end of the IMiD triplet. There was no significant difference between those who received thalidomide compared to lenalidomide (CTD: 110/1945, 5.7% CRD: 97/1949, 5.0%). A higher proportion of patients were refractory in the TNE pathway than TE (TE: 79/2042, 3.9%, TNE: 128/1852, 6.9%) 139 patients in the ITT population went on to receive treatment with bortezomib as part of the CVD regimen. The remainder n=69 were treated off protocol or died prior to treatment. CVD was well-tolerated in these patients with a median of 4 (1-8) cycles delivered. Of these patients 22/139 (16%) were also refractory to PI therapy whilst 57% upgraded their response compared to baseline: 32% [95%CI 24-40] to PR/MR and 25% [95%CI 18-33] to CR/VGPR. Patients with IMiD refractory disease had a significantly shorter PFS than those who responded to initial treatment median 8 vs 27 months, HR 2.10 [95% CI 1.77-2.49], p 〈 0.001. For those who received subsequent CVD (n=139) and responded the median PFS was 19 months vs 7 months for double refractory patients. 32/50 transplant eligible patients who responded to CVD were able to go on and receive a transplant and had a PFS of 27 months. We compared the clinical and biological features of the double-refractory (n=22), IMiD refractory (n=185) and responsive (n=3349) patient groups. There was no significant difference in patient sex or median age (66 [range 41-78], 70 [38-88] and 67 [28-92] respectively). Laboratory measures suggested refractory patients had a higher burden of disease at diagnosis with a lower hemoglobin level and a higher proportion of patients with 〉 20% plasma cells in their bone marrow biopsy. There was a higher proportion of patients with light chain only disease and the percentage of patients with ISS stage III was double-refractory 41%, IMiD refractory 45% and responsive 29%. The proportions of patients with adverse translocations and high-risk copy number abnormalities will be presented at the meeting. Conclusions We present the first detailed analysis of IMiD refractory myeloma patients at diagnosis. There was no difference in the percentage of patients refractory to the different IMiDs thalidomide and lenalidomide. Very few patients were primarily refractory to both IMiDs and proteasome inhibitors, suggesting the mechanisms of primary resistance to IMiDs and PIs do not significantly overlap. However, where this did occur outcomes were poor. The biological mechanisms behind resistance will be further informed by molecular studies of these patients' tumour samples. On behalf of the NCRI Haem Onc CSG Disclosures Pawlyn: Takeda Oncology: Consultancy; Celgene: Consultancy, Honoraria, Other: Travel Support. Davies:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Kaiser:Takeda: Consultancy, Other: Travel Support; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS: Consultancy, Other: Travel Support; Celgene: Consultancy, Honoraria, Research Funding; Chugai: Consultancy. Jones:Celgene: Honoraria, Research Funding. Kishore:celgene: Other: travel grant. Garg:Janssen: Other: Travel support, Research Funding, Speakers Bureau; Takeda: Other: Travel support; Novartis: Other: Travel support, Research Funding. Williams:Novartis: Honoraria; Janssen: Honoraria, Other: Travel support, Speakers Bureau; Celgene: Honoraria, Other: Travel support, Speakers Bureau; Takeda: Honoraria, Other: Travel support, Speakers Bureau; Amgen: Honoraria, Speakers Bureau. Karunanithi:Celgene: Other: Travel support, Research Funding; Janssen: Other: Travel support, Research Funding. Lindsay:BMS: Consultancy, Other: Travel support; Novartis: Other: Travel support; Takeda: Other: Travel support; Janssen: Consultancy; Celgene: Honoraria, Other: Travel support. Jenner:Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel support; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel support, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel support. Cook:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria. Drayson:Abingdon Health: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Owen:Takeda: Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Other: Travel support. Jackson:Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau. Morgan:Takeda: Consultancy, Honoraria; Bristol Meyers: Consultancy, Honoraria; Univ of AR for Medical Sciences: Employment; Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.1144.1144

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: The Lancet Oncology, Elsevier BV, Vol. 20, No. 1 ( 2019-01), p. 57-73

Type of Medium: Online Resource

ISSN: 1470-2045

URL: Article

DOI: 10.1016/S1470-2045(18)30687-9

Language: English

Publisher: Elsevier BV

Publication Date: 2019

detail.hit.zdb_id: 2049730-1

In: British Journal of Haematology, Wiley, Vol. 192, No. 5 ( 2021-03), p. 853-868

Abstract: Second‐generation immunomodulatory agents, such as lenalidomide, have a more favourable side‐effect profile than the first‐generation thalidomide, but their optimum combination and duration for patients with newly diagnosed transplant‐ineligible myeloma (ND‐TNE‐MM) has not been defined. The most appropriate delivery and dosing regimens of these therapies for patients at advanced age and frailty status is also unclear. The Myeloma XI study compared cyclophosphamide, thalidomide and dexamethasone (CTDa) to cyclophosphamide, lenalidomide and dexamethasone (CRDa) as induction therapy, followed by a maintenance randomisation between ongoing therapy with lenalidomide or observation for patients with ND‐TNE‐MM. CRDa deepened response but did not improve progression‐free (PFS) or overall survival (OS) compared to CTDa. However, analysis by age group highlighted significant differences in tolerability in older, frailer patients that may have limited treatment delivery and impacted outcome. Deeper responses and PFS and OS benefits with CRDa over CTDs were seen in patients aged ≤70 years, with an increase in toxicity and discontinuation observed in older patients. Our results highlight the importance of considering age and frailty in the approach to therapy for patients with ND‐TNE‐MM, highlighting the need for prospective validation of frailty adapted therapy approaches, which may improve outcomes by tailoring treatment to the individual.

Type of Medium: Online Resource

ISSN: 0007-1048 , 1365-2141

URL: Issue

URL: Article

DOI: 10.1111/bjh.v192.5

DOI: 10.1111/bjh.16945

Language: English

Publisher: Wiley

Publication Date: 2021

detail.hit.zdb_id: 1475751-5

In: Blood, American Society of Hematology, Vol. 132, No. Supplement 1 ( 2018-11-29), p. 302-302

Abstract: Background Darwinian evolution drives multiple myeloma (MM) and leads to diversity both within and between patients. This suggests the need for combinations of agents with different mechanisms of action targeting sub-clonal populations to maximize the depth of response and improve outcomes. Approaches to maximize response pre-transplant include the use of sequential pre-transplant consolidation with a different agent in sub-optimal responders or intensifying upfront combinations whilst aiming to minimize additional toxicities. Carfilzomib is a novel irreversible inhibitor of the proteasome that has been suggested to have greater activity than bortezomib, with deeper responses and improved outcomes. The Myeloma XI phase III randomized trial for newly diagnosed MM patients compared intensified induction with the quadruplet KCRD vs a response adapted approach of sequential triplet therapies for transplant-eligible MM patients. Methods KCRD was given in 28 day cycles (carfilzomib (K) 36mg/m2 IV d1-2, 8-9,15-16 (20mg/m2 #1d1-2), cyclophosphamide (C) 500mg PO d1,8, lenalidomide (R) 25mg PO d1-21, dexamethasone (D) 40mg PO d1-4,8-9,15-16), CRD in 28 day cycles (C 500mg PO d1,8, R 25mg PO d1-21, D 40mg PO d1-4, 12-15) or CTD in 21 day cycles (C 500mg PO d1,8,15 thalidomide (T) 100-200mg PO daily, D 40mg PO d1-4,12-15). All induction regimens were continued for a minimum of 4 cycles and to maximum response. Suboptimal responders (MR/PR) to CTD/CRD were randomized between pre-transplant intensification with a proteasome inhibitor (bortezomib, CVD) containing triplet or no further therapy prior to ASCT, patients with refractory disease (SD/PD) all received CVD. For all patients a maintenance randomization 3 months post ASCT compared lenalidomide given to disease progression to observation. Cytogenetic data, centrally analyzed, was available for a representative subset of patients. High-risk was classified as presence of t(4;14), t(14;16), t(14;20), del(17p) or gain(1q) and ultra-high risk the presence of more than one lesion. 1056 patients underwent induction randomization between December 2013 and April 2016 and were allocated to CTD n=265, CRD n=265, KCRD n=526. The groups were well matched across baseline variables with median age 61 (range 33-75). The median follow up for this analysis is 34.5 months. The independent data monitoring and ethics committee recommended immediate release of the data following an interim analysis. Results Intention to treat analysis of the initial induction regimens found that KCRD was associated with a significantly longer PFS than triplet therapy (HR 0.63, 95%CI 0.51, 0.76, median PFS KCRD NR vs CTD/CRD 36.2 months, p 〈 0.0001). Improved PFS was seen in all cytogenetic risk groups. PFS2, a key secondary endpoint, was also significantly improved with KCRD (HR 0.75, 95% CI 0.56, 0.99, 3yr PFS2 KCRD 81.8% vs CTD/CRD 75.1%). Deeper response rates were seen in patients treated with KCRD vs CTD/CRD both pre and post transplant (p 〈 0.0001), Table 1. All regimens were well tolerated with no significant additional toxicity due to the quadruplet regimen. KCRD was administered for a median of 4 cycles, CRD 5 cycles and CTD 6 cycles. Grade 3+ neutropenia occurred in 16.4% KCRD, 22.3% CRD and 12.8% CTD patients and thrombocytopenia in 8.4% KCRD, 2.3% CRD and 1.2% CTD patients. A higher proportion of patients receiving KCRD induction were able to undergo ASCT than those who received response-adapted induction. In an analysis restricted to those who had completed ASCT, KCRD induction was still associated with a significantly longer PFS. An exploratory analysis compared the patients receiving KCRD to patients in the CTD/CRD arm who had received the optimum response-adapted approach (i.e. excluding those randomized to no CVD following MR/PR). The quadruplet was associated with significantly longer PFS than using a response adapted sequential triplet approach (HR 0.64, 95% CI 0.52, 0.78, p 〈 0.0001). Conclusions This large randomized study of a carfilzomib containing quadruplet combination, KCRD, demonstrates that it is well tolerated and associated with deep responses both pre- and post-transplant and has a significant PFS and PFS2 benefit compared to triplet therapy. The benefit of upfront intensification of treatment persisted even compared to triplets administered sequentially and including exposure to both lenalidomide and bortezomib. On behalf of the NCRI Haem-oncology CSG Disclosures Jackson: Merck Sharp and Dohme: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Roche: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel Support, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel Support, Research Funding, Speakers Bureau. Davies:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy; ASH: Honoraria; MMRF: Honoraria; Janssen: Consultancy, Honoraria; TRM Oncology: Honoraria. Pawlyn:Janssen: Honoraria, Other: Travel support; Celgene Corporation: Consultancy, Honoraria, Other: Travel support; Amgen: Consultancy, Honoraria, Other: Travel Support; Takeda Oncology: Consultancy, Other: Travel support. Cairns:Merck Sharp and Dohme: Research Funding; Amgen: Research Funding; Celgene: Research Funding. Striha:Amgen: Research Funding; Abbvie: Research Funding; MSD: Research Funding; Celgene: Research Funding; Janssen: Research Funding. Hockaday:MSD: Research Funding; Janssen: Research Funding; Celgene: Research Funding; Amgen: Research Funding; Abbvie: Research Funding; Millenium: Research Funding. Collett:Amgen: Research Funding; Celgene: Research Funding; Merck Sharp and Dohme: Research Funding. Jones:Celgene: Honoraria, Other: Travel support, Research Funding. Kishore:Takeda: Honoraria, Other: travel support; Celgene: Honoraria. Garg:Novartis: Other: travel support, Research Funding; Amgen: Honoraria, Other: Travel Support; Janssen: Honoraria; Takeda: Other: Travel Grant. Williams:Amgen: Honoraria, Speakers Bureau; Novartis: Honoraria; Janssen: Honoraria, Other: travel support, Speakers Bureau; Takeda: Honoraria, Other: travel support, Speakers Bureau; Celgene: Honoraria, Other: travel support, Speakers Bureau. Karunanithi:Janssen: Other: Travel support, Research Funding; Celgene: Other: Travel support, Research Funding. Lindsay:Takeda: Other: Travel support; BMS: Consultancy, Other: Travel support; Janssen: Consultancy; Celgene: Honoraria, Other: Travel support; Novartis: Other: Travel support. Jenner:Celgene: 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; Takeda: 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. Cook:Celgene Corporation: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Seattle Genetics: Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Glycomimetics: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria, Speakers Bureau. Russell:Jazz Pharma: Speakers Bureau; Daiichi Sankyo: Consultancy; Pfizer: Consultancy, Honoraria, Speakers Bureau. Kaiser:Bristol-Myers Squibb: Consultancy, Other: travel support; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Other: travel support; Janssen: Consultancy, Honoraria; Chugai: Consultancy; 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; Janssen: Honoraria; Amgen: Research Funding; Merck Sharp and Dohme: Research Funding. Morgan:Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2018-99-114956

Language: English

Publisher: American Society of Hematology

Publication Date: 2018

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 244-244

Abstract: Background The Myeloma XI study is the first randomized study to investigate a response-adapted approach to induction therapy for newly diagnosed myeloma (NDMM). The study addresses whether, for patients achieving less than optimum response to an initial immunomodulatory (IMiD) triplet combination, defined as at least VGPR, the use of a sequential proteasome inhibitor (PI) based triplet can improve outcomes. In total 581 patients were randomized into the study which confirms the clinically significant benefit of deepening responses by utilizing treatment with a different mode of action, and that this leads to better outcomes. Methods This phase III, UK-based, multicenter, open-label, parallel group, randomized controlled trial for NDMM patients of all ages, randomized patients initially between a thalidomide or lenalidomide triplet combination with cyclophosphamide and dexamethasone. This IMiD triplet was continued for a minimum of 4 cycles (transplant eligible, TE) or 6 cycles (transplant non-eligible, TNE) and to maximum response. At the end of this IMiD regimen response was assessed. Patients with a suboptimal response (MR/PR) were randomized between further induction therapy with bortezomib, cyclophosphamide and dexamethasone (CVD) or no further induction therapy. Patients with a good response (VGPR/CR) proceeded straight to ASCT (if TE), whilst refractory (SD/PD) patients all received the CVD regimen. For patients receiving CVD, treatment was planned to continue to maximum response, and eligible patients would proceed to ASCT. The primary endpoints of the adapted approach randomization were progression-free survival (PFS) and overall survival. Secondary endpoints included upgrading of response compared to baseline and the impact of the PI combination in a high-risk subgroup. This abstract contains a preliminary analysis, final data will be presented at the meeting. The median follow up in this analysis is 29 months [IQR 17-44]. Results 581 patients (366 TE, 215 TNE) with initial response to IMiD of MR/PR were entered into the CVD randomization. In total 292/581 patients were randomized to receive sequential treatment with CVD. The arms were well-balanced with respect to clinical features and response (e.g. ISS stage: III 21% vs 19%, PR: 88% vs 88%). This randomization has met its primary endpoint. Overall the sequential use of CVD significantly improved PFS from a median of 24 to 30 months (HR 0.67 [95%CI 0.53-0.85], p=0.0005). This was largely due to a significant improvement seen in the TE pathway, HR 0.56 [95%CI 0.40-0.77] , median PFS no therapy 31 months vs CVD 55 months, p=0.0003. In the TNE pathway there was an early benefit with improved median PFS 14 months vs 20 months, but similar hazard after 2 years (HR 0.83 [95%CI 0.60-1.17], p=0.297). Importantly upgrading of response was seen with 118/289 (41% [95%CI 35-47]) of evaluable patients who received CVD moving from MR/PR to VGPR/CR. 115/289 remained in the same response category MR/PR, but these patients still had a mean reduction in paraprotein during CVD of 24% [95%CI 11-17] . The upgrade in response was seen in both pathways and was not affected by the IMiD received in the initial induction randomization. The impact of CVD in cases with molecularly defined high-risk disease compared to standard and multiparameter flow cytometry assessment of minimal residual disease status will be presented at the meeting. In the transplant eligible pathway an improved depth of response persisted in the 253 patients completing ASCT with VGPR/CR responses post ASCT of 65% for those who were randomized to CVD (VGPR n=133, CR n=86) compared to 38% for those who went straight to transplant (VGPR n=120, CR n=46). Sequential CVD was well tolerated with patients receiving a median of 4 cycles of therapy (range 1-8). Relevant grade 3/4 toxicities were: neutropenia 7.1%, thrombocytopenia 7.5%, anaemia 3.1%, peripheral neuropathy 5.1%. Conclusion For the first time we have shown that the use of a response-adapted therapy based on the use of chemotherapeutic agents with a different mode of action in myeloma can improve response rates, both pre- and post-transplant and that these translate into improved PFS. On behalf of the NCRI Haem-Onc CSG Disclosures Jackson: Roche: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau. Davies:Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Celgene: Consultancy, Honoraria. Pawlyn:Celgene: Consultancy, Honoraria, Other: Travel Support; Takeda Oncology: Consultancy. Jones:Celgene: Honoraria, Research Funding. Kishore:celgene: Other: travel grant. Garg:Janssen: Other: Travel support, Research Funding, Speakers Bureau; Takeda: Other: Travel support; Novartis: Other: Travel support, Research Funding. Williams:Takeda: Honoraria, Other: Travel support, Speakers Bureau; Janssen: Honoraria, Other: Travel support, Speakers Bureau; Celgene: Honoraria, Other: Travel support, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Novartis: Honoraria. Karunanithi:Celgene: Other: Travel support, Research Funding; Janssen: Other: Travel support, Research Funding. Lindsay:Novartis: Other: Travel support; Janssen: Consultancy; Takeda: Other: Travel support; BMS: Consultancy, Other: Travel support; Celgene: Honoraria, Other: Travel support. Jenner:Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Other: Travel support, Research Funding; Takeda: Consultancy, Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Other: Travel support. Cook:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria; Glycomimetics: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Kaiser:BMS: Consultancy, Other: Travel Support; Takeda: Consultancy, Other: Travel Support; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Chugai: Consultancy. Drayson:Abingdon Health: Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Owen:Takeda: Honoraria, Other: Travel support; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Other: Travel support. Morgan:Bristol Meyers: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Research Funding; Univ of AR for Medical Sciences: Employment; Celgene: Consultancy, Honoraria, Research Funding.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood.V128.22.244.244

Language: English

Publisher: American Society of Hematology

Publication Date: 2016

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7