Among patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation, daratumumab combined with bortezomib, melphalan, and prednisone resulted in a lower risk of disease progression or death than the same regimen without daratumumab. The daratumumab-containing regimen was associated with more grade 3 or 4 infections. (Funded by Janssen Research and Development; ALCYONE ClinicalTrials.gov number, NCT02195479 .).

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AperTO -Archivio Istituzionale Open Access dell'Università di TorinoChemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: A randomised, multicentre, phase 3 trial / Gay, Francesca; Oliva, Stefania; Petrucci, Maria Teresa; Conticello, Concetta; Catalano, Lucio; Corradini, Paolo; Siniscalchi, Agostina; Magarotto, Valeria; Pour, Ludk; Carella, Angelo; Malfitano, Alessandra; Petrò, Daniela; Evangelista, Andrea; Spada, Stefano; Pescosta, Norbert; Omedè, Paola; Campbell, Philip; Liberati, Anna Marina; Offidani, Massimo; Ria, Roberto; Pulini, Stefano; Patriarca, Francesca; Hajek, Roman; Spencer, Andrew; Boccadoro, Mario; Palumbo, Antonio. -In: LANCET ONCOLOGY. -ISSN 1470-ISSN -2045-ISSN . -16:16(2015, pp. 1617-1629. Original Citation:Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: A randomised, multicentre, phase 3 trial This is an author version of the contribution published on:Questa è la versione dell'autore dell'opera: [Lancet Oncol. 2015 Dec;16(16):1617-29. doi: 10.1016/S1470-2045 Background. High-dose melphalan plus autologous stem-cell transplantation (MEL200-

There are few Australian data on the incidence of catheter-associated bloodstream infection (BSI) among patients in hematology-oncology units. We found an increase in catheter-associated BSI rates coincident with the introduction of a mechanical valve connector (2.6 infections vs 5.8 infections per 1,000 catheter-days; incidence rate ratio, 2.2; P=.031).

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In newly diagnosed myeloma patients, upfront autologous transplant (ASCT) prolongs progression-free survival 1 (PFS1) compared with chemotherapy plus lenalidomide (CC+R). Salvage ASCT at first relapse may still effectively rescue patients who did not receive upfront ASCT. To evaluate the long-term benefit of upfront ASCT vs CC+R and the impact of salvage ASCT in patients who received upfront CC+R, we conducted a pooled analysis of 2 phase III trials (RV-MM-209 and EMN-441). Primary endpoints were PFS1, progression-free survival 2 (PFS2), overall survival (OS). A total of 268 patients were randomized to 2 courses of melphalan 200 mg/m and ASCT (MEL200-ASCT) and 261 to CC+R. Median follow-up was 46 months. MEL200-ASCT significantly improved PFS1 (median: 42 vs 24 months, HR 0.53; P<0.001), PFS2 (4 years: 71 vs 54%, HR 0.53, P<0.001) and OS (4 years: 84 vs 70%, HR 0.51, P<0.001) compared with CC+R. The advantage was noticed in good and bad prognosis patients. Only 53% of patients relapsing from CC+R received ASCT at first relapse. Upfront ASCT significantly reduced the risk of death (HR 0.51; P=0.007) in comparison with salvage ASCT. In conclusion, these data confirm the role of upfront ASCT as the standard approach for all young myeloma patients.

Introduction: Relapsed/refractory (R/R) follicular lymphoma (FL) remains a difficult-to-treat condition, with limited treatment options. New, tolerable treatments with unique mechanisms of action are needed, especially for high-risk patients whose disease progresses within 24 months of diagnosis (POD24). The epigenetic regulator EZH2 catalyzes the histone 3 lysine 27 trimethylation (H3K27m3) gene suppressive mark, which is essential for BCL6-driven germinal center (GC) formation. Conversely, a reduction in EZH2 catalytic activity is required for centroblast differentiation and initiation of the GC exit program. Activating mutations (MT) in EZH2, present in ~20% of FL patients, and enhanced H3K27me3 prevent GC exit, resulting in GC hyperplasia and lymphomagenesis. Tazemetostat, an investigational, selective, oral EZH2 inhibitor, has demonstrated durable, single-agent, antitumor activity in R/R FL patients with MT or wild-type (WT) EZH2. Herein, we report newly emerging interim efficacy and safety data from the MT and WT cohorts and the POD24 subgroup. Methods: This open-label, multicenter, phase 2 study (NCT01897571) evaluated tazemetostat 800 mg administered orally twice daily in patients with MT or WT EZH2 R/R FL (Grade 1-3b). Key inclusion criteria included age ≥18 years, Eastern Cooperative Oncology Group performance status of 0-2, ≥2 prior treatment regimens, and measurable disease per 2007 IWG-NHL criteria. The primary endpoint was objective response rate (complete response + partial response). Secondary endpoints included progression-free survival and safety. The POD24 subgroup was composed of patients experiencing disease progression or relapse within 24 months of diagnosis or the start of frontline treatment with immunochemotherapy. Results: As of June 7, 2019, interim data were available for 99 patients (MT EZH2, n=45 [POD24, n=17; 38%]; WT EZH2, n=54 [POD24, n=30; 56%]). Of the 33 patients in the MT cohort with an objective response, 15 (45%) had a response at ≥6 months, 7 (21%) at ≥12 months, and 4 (12%) at ≥16 months. Of the 18 patients in the WT cohort with an objective response, 15 (83%) had a response at ≥6 months, 9 (50%) at ≥12 months, and 6 (33%) at ≥16 months. Data from the MT cohort continue to mature, with 11 (24%) patients enrolled in the past year and 17 (38%) patients still on treatment. Updated data from the fully enrolled MT cohort, and sub-group analyses from both WT and MT cohort, will be presented. Interim efficacy data from the response-evaluable population and POD24 subgroup of the MT and WT cohorts are presented in Table 1. These results demonstrate the potent, antitumor activity of tazemetostat regardless of the prognostic category of patients. Treatment-related Grade ≥3 adverse events (AEs) were reported in 17% of all patients and 15% of patients in the POD24 subgroup. The most frequently reported AEs were similar across the total population and the POD24 subgroup and included thrombocytopenia (3%), anemia (2%), asthenia (2%), vomiting (1%), and fatigue (1%). Five percent of all patients discontinued treatment, and 9% had dose reductions due to treatment-related AEs. No treatment-related Grade 5 AE and deaths were reported. Conclusion: Tazemetostat was generally well tolerated, with a low incidence of treatment-related AEs. Tazemetostat demonstrated clinically meaningful, durable, single-agent activity across a spectrum of patients with FL, including the POD24 subgroup, and pronounced responses in patients with EZH2 activating mutations. Disclosures Morschhauser: BMS: Honoraria; Roche/Genentech: Consultancy; Servier: Consultancy; Janssen: Honoraria; Celgene: Honoraria; Gilead: Consultancy. Tilly:servier: Honoraria; merck: Honoraria; roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Gilead: Honoraria; BMS: Honoraria; Karyopharm: Consultancy; Roche: Consultancy; Celgene: Consultancy, Research Funding; Astra-Zeneca: Consultancy. Phillips:Bayer: Consultancy; Incyte: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Consultancy; Seattle Genetics: Consultancy; Gilead: Consultancy; Abbvie: Research Funding; Pharmacyclics: Consultancy, Research Funding. Ribrag:Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Epizyme: Consultancy, Research Funding; ArgenX: Research Funding; MSD: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; AZ: Membership on an entity's Board of Directors or advisory committees; Nanostring: Membership on an entity's Board of Directors or advisory committees; Roche: Other: Travel, accommodations, and expenses ; BMS: Membership on an entity's Board of Directors or advisory committees, Other: Travel, accommodations, and expenses . Campbell:Janssen: Honoraria, Research Funding, Speakers Bureau. Jurczak:Servier: Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Research Funding; Takeda: Research Funding; Bayer: Research Funding; Celgene: Research Funding; Roche: Research Funding; Morphosys: Research Funding; TG Therapeutics: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celtrion: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Gilead: Research Funding; AstraZeneca/Acerta: Membership on an entity's Board of Directors or advisory committees, Research Funding. McKay:Epizyme: Consultancy, Honoraria. Opat:Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Mundipharma: Consultancy, Honoraria. Radford:GSK: Equity Ownership; ADC Therapeutics: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; AstraZeneca: Equity Ownership, Research Funding; Novartis: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria. Whalen:Epizyme: Employment, Equity Ownership. Rajarethinam:Epizyme: Employment, Equity Ownership. Navia:Epizyme: Employment, Equity Ownership. Adib:Epizyme: Employment, Equity Ownership. Salles:Amgen: Honoraria, Other: Educational events; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Epizyme: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis, Servier, AbbVie, Karyopharm, Kite, MorphoSys: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Roche, Janssen, Gilead, Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Educational events.

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