Between January 2001 and June 2008, 315 adult patients (median age 43 years, range 16-65) including 203 males and 112 females undergoing hematopoietic stem cell transplantation (HSCT) had serial monitoring for cytomegalovirus (CMV) followed by initiation of preemptive therapy. The majority (62.1%) had a conventional myeloablative transplant with 116 (36.9%) having a reduced-intensity conditioning (RIC) transplant, using either matched sibling/family (63.3%) or unrelated donors (36.7%). Graft source was peripheral blood stem cells in 257 (81.5%), bone marrow in 41 (13.1%), and cord blood in 16 (5.4%). T-cell depletion with anti-thymocyte globulin or alemtuzumab was used in 35%. Based upon CMV serostatus, patients were classified into low risk (donor [D]-/recipient [R]-), intermediate risk (D+/R-), or high risk (D-/R+ or D+/R+). Serial weekly monitoring for CMV viremia was performed using a qualitative polymerase chain reaction (PCR) and when positive, quantification was done using either pp65 antigen or a quantitative PCR. CMV reactivation was seen in 123 patients (39.1%) at a median of 50 days post HSCT (range 22-1978). CMV serostatus was the most important risk factor with incidence of 53% in the high-risk group (53.3%) compared with 10.2% in the intermediate risk and 0% in the low-risk group (P<0.0001). Other significant risk factors identified included use of alemtuzumab during conditioning (P=0.03), RIC transplants (P=0.06), and the presence of acute graft-versus-host disease (GVHD) (P<0.0001). On a multivariate analysis, CMV serostatus, RIC transplants, and acute GVHD remained independent predictors of CMV reactivation. All were treated with antiviral therapy with responses seen in 109 (88.6%). Sixteen patients (13%) developed CMV disease at a median of 59 days post HSCT (range 26 days-46 months), 8 of whom died. At a median follow up of 43 months (range 6-93), 166 patients (52.6%) are alive with a significantly higher survival among patients without CMV reactivation (57.2%) as compared with patients with CMV reactivation (45.5%; P=0.049). CMV reactivation and disease remains a major problem in high-risk patients undergoing allogeneic HSCT. Novel prophylactic measures such as immunotherapy and drug prophylaxis need to be considered in this specific group of patients.
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The pharmacokinetics of oral busulphan given four times daily has been extensively studied. • Large inter‐ and intravariability in oral busulphan exposure has led to attempts at pharmacokinetic monitoring. • However, there have been limitations in the pharmacokinetic analysis due to inadequate characterization of the elimination phase in a 6‐h dosing interval, due to late absorption in some patients. • Intravenous (i.v.) busulphan is a relatively new administration method and there have been relatively few studies on the pharmacokinetics of i.v. busulphan, especially when given as a single daily dose. WHAT THIS STUDY ADDS • Inter‐ and intrapatient variability in i.v. busulphan pharmacokinetics is comparable to that previously observed with oral busulphan, suggesting that pharmacokinetic monitoring is advisable. • Children with immune deficiencies, in particular, have widely variable exposure. AIM To examine inter‐ and intrapatient variability in the pharmacokinetics of intravenous (i.v.) busulphan given as a single daily dose to children with malignant (n = 19) and nonmalignant (n = 21) disease. METHODS Busulphan (120 mg m−2, 130 mg m−2 or 3.2 mg kg−1) was administered over median 2.1 h. Blood samples (4–10) were collected after the first dose, busulphan concentrations were measured and pharmacokinetic parameters, including clearance (CL) and area under the concentration–time curve (AUC), were determined using the Kinetica software (Innaphase). Interpatient variability was assessed as percent coefficient of variation (% CV). Intrapatient variability was assessed by calculating percent differences between observed full dose AUC and AUC predicted from an initial 65 mg m−2 dose in 13 children who had busulphan pharmacokinetic monitoring. RESULTS Clearance of i.v. busulphan in 40 children was 4.78 ± 2.93 l h−1 (% CV 61%), 0.23 ± 0.08 l h−1 kg−1 (% CV 35%) and 5.79 ± 1.59 l h−1 m−2 (% CV 27%). Age correlated significantly (p < 0.001) with CL (l h−1) and CL (l h−1 kg−1), but not with CL (l h−1 m−2). AUC normalized to the 130 mg m−2 dose ranged from 14.1 to 56.3 mg l−1.h (% CV 37%) and also did not correlate with age. Interpatient variability in CL (l h−1 m−2) was highest in six children with immune deficiencies (60%) and lowest in seven children with solid tumours (14%). Intrapatient variability was <13% for nine (of 13) children, but between 20 and 44% for four children. CONCLUSIONS There is considerable inter‐ and intrapatient variability in i.v. busulphan CL (l h−1 m−2) and exposure that is unrelated to age, especially in children with immune deficiencies. These results suggest that monitoring of i.v. busulphan pharmacokinetics is required.
Introduction R-mini-CHOP is an established standard of care in elderly patients with DLBCL, with a 2yr OS of 59% and PFS of 47% (Peyrade et al, Lancet Oncol 2011). The addition of ibrutinib to full dose R-CHOP in younger pts with DLBCL has efficacy, but significant toxicity limits the ability to complete therapy in pts ≥60 yrs (Younes et al, JCO 2019). We previously demonstrated the deliverability of ibrutinib with R-mini-CHOP in 80 pts ≥75yrs with DLBCL with a median average relative total dose of 97%; 77% of pts received 6 cycles of R-mini-CHOP despite SAEs in 62% (Verner et al, Haematol Oncol 2019). Here we present the primary efficacy endpoint and key secondary and exploratory endpoints. Methods This was a prospective, multicenter, single-arm, phase 2 study of patients aged ≥75yrs with newly diagnosed DLBCL. Pts received six 21-day cycles of ibrutinib 560mg/d and R-mini-CHOP (Rituximab 375mg/m 2, cyclophosphamide 400mg/m 2, doxorubicin 25mg/m 2, vincristine 1mg on day 1 & prednisone 40mg/m 2 or 100mg/d x 5) followed by an additional two 21-day cycles of rituximab + ibrutinib (or high dose methotrexate for CNS prophylaxis). The efficacy primary endpoint was 2yr OS. Sample size calculations were made using a one-sample two-sided approach to detect a 15% improvement on the fixed reference OS (59%) and PFS (47%) rates (Peyrade et al, Lancet Oncol 2011). Results Eighty pts were recruited from Nov 2015 to Dec 2018. One died prior to receiving treatment and is not included in the analysis. Median age was 82yrs (75-95); 51% female, 81% stage III/IV and 63% IPI 3-5: 47% had a CIRS-G score of ≥6 (range 0-17). On centralized immunohistochemistry (IHC), 57% (45/79) were non-Germinal Centre B cell-like (GCB) subtype; 43% (34/79) were GCB. At a data cut-off of 6June 21, median follow-up was 29.5 months (m) (0.2 to 66.3). Two-year OS was 68% (95% CI 55-77%), not differing significantly from the null hypothesis of 59% (p=0.10), (Figure 1A). Median OS was not reached (NR) (95% CI 34m to NR), and was longer in those with lower IPI (IPI 1-3: NR, IPI 4: 35m, IPI 5: 19m). Two-year PFS was 60% (95% CI 47-70%), significantly different from the reference 47% (p<0.03), (Figure 1B). Median PFS was NR (95% CI 20m to NR). Two-year DFS was 85% (95% CI 60-95%), median NR (95% CI 32m to NR). COO had no impact on either 2yr OS [median GCB NR (95% CI 29m to NR), median non-GCB NR (95% CI 24m to NR) p=0.99] or 2yr PFS [median GCB 39m (95% CI 17m to NR), median non-GCB NR (95% CI 19m to NR) p=0.97]. Cause of death in 28/79 pts (35%) was: 16 progressive lymphoma, 5 infection, 2 respiratory failure, 2 other malignancy, 1 cardiac arrest, 1 intra-abdominal hemorrhage, 1 gastric hemorrhage. At least one adverse event (AE) occurred in 99% pts (78/79): 30% (24/79) grade 1-2, 64% (49/79) grade 3-4, and 6% (5/79) grade 5. Most common grade ≥3 AEs were lung infection (13%), other infections (11%), anemia (11%), febrile neutropenia (9%), thrombocytopenia (9%), and atrial fibrillation (8%). Serious AEs occurred in 67%: most commonly lung infection (11%), atrial fibrillation (9%), fever (9%), and other infection (9%). 12/14 pts with atrial fibrillation/flutter were new onset. Ibrutinib was temporarily ceased in 62% of patients, and permanently ceased in 25%, mostly due to adverse events. As previously reported, the overall response rate on an intention to treat basis was 57/80 (71%) (Verner et al, ASH 2019). Response rates did not differ by cell of origin (COO) (ORR: non-GCB 76%, GCB 68% p=0.44). When recorded, pt's EORTC-QLQ-C30 global health status significantly improved between screening [n=78; mean (SD) 58(25)], end of treatment [n=57; 63(23)] and 18mo post-treatment [n=29; 74(19)] p=0.007. Significant reductions in fatigue, nausea and vomiting, pain, insomnia, appetite loss, constipation and diarrhea were also observed in respondents. There was no impact of CIRS-G score on disease response rate or risk of death. Conclusion The addition of ibrutinib to R-mini-CHOP was deliverable and improved 2-yr PFS compared to R-mini-CHOP alone. However, while there was a trend towards improvement in 2-yr OS, a target 15% increase was not achieved in this small sample size. Despite considerable and not unexpected toxicity in this elderly cohort, the QOL and functional improvements in survivors are also promising. These data support further study of the addition of ibrutinib to R-mini-CHOP in elderly patients with DLBCL. Figure 1 Figure 1. Disclosures Verner: Janssen-Cilag Pty Ltd: Research Funding. Hawkes: Merck KgA: Research Funding; Bristol Myers Squib/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Specialised Therapeutics: Consultancy; Antigene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees; Regeneron: Speakers Bureau; Merck Sharpe Dohme: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel and accommodation expenses, Research Funding, Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Lee: Roche: Honoraria; BeiGene: Membership on an entity's Board of Directors or advisory committees. Cheah: BMS: Consultancy, Research Funding; Abbvie: Research Funding; Janssen: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Ascentage Pharma: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Lilly: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Other: travel, Research Funding. Purtill: Novartis: Honoraria; Gilead: Honoraria; BMS Celgene: Honoraria. Enjeti: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Speakers Bureau; AbbVie: Honoraria; Sanofi: Honoraria; Astra Zeneca: Honoraria. Curnow: Bayer: Consultancy, Research Funding; Pfizer/BMS: Consultancy, Honoraria; Mylan: Consultancy; Norgine: Consultancy, Honoraria. Butcher: WriteSource: Current Employment, Other: Medical writing for Pharma companies. Not pertinent to this abstract for which author is study Statisticiam. Trotman: JANSSEN: Research Funding; TAKEDA: Research Funding; BMS: Research Funding; PCYC: Research Funding; roche: Research Funding; beigene: Research Funding. OffLabel Disclosure: Ibrutinib is not approved for use in DLBCL
The advent of pediatric inspired regimens has improved the outcome for younger adults with Acute Lymphoblastic Leukemia (ALL), however this comes at a considerable toxicity burden limiting its applicability in older adults. The advent of novel immunotherapies, such as Blinatumomab, an anti-CD19 targeting Bi-specific T-cell engager, has improved outcomes for adults with relapsed refractory and minimal residual disease (MRD) positive B-precursor (BCP) ALL. The Australasian Leukemia and Lymphoma Group (ALLG) undertook a phase 2 proof-of-concept study to explore the combination of Blinatumomab with reduced intensity chemotherapy in adults with newly diagnosed Ph- BCP ALL. Patients received an initial pre-phase of corticosteroids (Prednisolone 100mg/d, 5 days) followed by a low intensity chemotherapy debulking (Cyclophosphamide 150mg/m 2 BD D1-3, Vincristine 2mg IV D1, 11 and Dexamethasone 10mg/m 2 D1-4, D11-14). Following this patients received Blinatumomab at 9mcg/d days 1-7 and 28mcg/d days 8-28. A B cycle of Hyper-CVAD (Cytarabine 3g/m 2 BD for 4 doses and Methotrexate 1g/m 2 D1 with Methylprednisolone 50mg BD D1-3). Patients then received 3 alternating cycles of Blinatumomab (28mcg/d for 28 days) and B-cycles of Hyper-CVAD followed by 2-years of POMP maintenance in subjects not proceeding to allogeneic stem cell transplant (alloHSCT) which was at investigator discretion. MRD assessments by ASO-PCR were performed after the first B cycle, second B cycle and prior to maintenance therapy with an MRD response being a level of 10 -4 or less. This analysis is from a pre-specified interim analysis with a data cutoff of 29 th June 2021. 30 patients were enrolled with a median age of 51.7(range, 39.5 - 66.5 years) with 70% male subjects. ECOG performance score was 0 in 14 subjects, 1 in 12 and 2 in 4. High risk disease was identified in 5 subjects (1 t(4;11), 2 hypodiploid, 1 t(1;19) and 1 Ph-like). All patients attained a CR, with 28 at end of 1B and a further 2 at end of 2B. Of 26 patients evaluable for MRD, 70% had achieved an MRD response after cycle 1B and 83% at the end of cycle 2B. 15 patients have ceased study therapy; 6 patients died with progressive disease, 4 subjects exited to allogeneic stem cell transplant, 1 patient was withdrawn due to progressive disease, 1 had intolerable toxicity (peripheral neuropathy) and 1 at investigator discretion. There were no treatment related deaths. 15 remain on protocol in maintenance with the remainder having completed therapy. At data cut-off the median event free survival (EFS) was not reached (95% CI 8.3 months - NA) with an estimated 24 month EFS of 61.8% (95% CI 36.3 - 84.2%) (figure 1A), and similarly the median overall survival (OS) S was not reached (95% CI 21.0 months - NA) with an estimated 24 month OS of 68.6% (95% CI 41.5 - 85.1%)(figure 1B). This predicted EFS was greater than the pre-specified stopping rule of a 24-month EFS of 50%. 2 episodes of cytokine release syndrome (CRS) were recorded (1 grade 2, 1 grade 3) with the major toxicity being infective (53 episodes of sepsis, infection or febrile neutropenia) predominately related to chemotherapy cycles. 7 episodes of neurological toxicity were demonstrated (1 myelopathy and 4 peripheral neuropathy occurring during chemotherapy and 2 encephalopathy occurring during Blinatumomab administration). Overall, the combination of Blinatumomab with chemotherapy was tolerable and appeared efficacious with a high rate of remission and deep MRD responses observed. Responses appeared durable despite a low rate of alloHSCTin first remission. The major toxicity was infective and occurred in the context of chemotherapy cycles. Future developments from this protocol will emphasise further reduction in cytotoxic chemotherapy through incorporation of further novel agents to minimise this toxicity. Figure 1 Figure 1. Disclosures Fleming: Servier: Honoraria; Pfizer: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Amgen: Honoraria, Research Funding, Speakers Bureau. Reynolds: Abbvie: Research Funding; Novartis AG: Current equity holder in publicly-traded company; Alcon: Current equity holder in publicly-traded company. Bajel: Abbvie, Amgen, Novartis, Pfizer: Honoraria; Amgen: Speakers Bureau. Yeung: BMS: Honoraria, Research Funding; Pfizer: Honoraria; Amgen: Honoraria; Novartis: Honoraria, Research Funding. Verner: Janssen-Cilag Pty Ltd: Research Funding. Wei: Abbvie, Amgen, Astellas, AstraZeneca, Celgene/BMS, Genentech, Janssen, MacroGenics, Novartis, Pfizer, and Servier: Honoraria; Novartis, Abbvie, Celgene/BMS: Speakers Bureau; Servier: Consultancy; Abbvie, Amgen, AstraZeneca, Celgene/BMS, Novartis, Servier and F. Hoffmann-La Roche: Research Funding; Abbvie, Amgen, Astellas, AstraZeneca, Celgene/BMS, Genentech, Janssen, MacroGenics, Novartis, Pfizer, and Servier: Membership on an entity's Board of Directors or advisory committees; Former employee of Walter and Eliza Hall Institute: Patents & Royalties: Prof. Andrew Wei is a former employee of the Walter and Eliza Hall Institute and is eligible for a fraction of the royalty stream related to Venetoclax. Greenwood: Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: Blinatumomab - usage in front-line therapy for Acute Lymphoblastic Leukaemia
PURPOSE To describe the establishment of an oncology unit at the National Referral Hospital (NRH) in the Solomon Islands, a low-income nation in the South Pacific. METHODS A scoping visit was carried out in 2016 to assist in the development of coordinated cancer services and to establish a medical oncology unit at the NRH at the request of the Medical Superintendent. This was followed by an observership visit to Canberra by an NRH doctor training in oncology in 2017. After a request from the Solomon Islands Ministry of Health, the Australian Government Department of Foreign Affairs and Trade (DFAT) arranged an in-country multidisciplinary mission under the Royal Australasian College of Surgeons/Royal Australasian College of Physicians Pacific Islands Program to help in the commissioning of the NRH Medical Oncology Unit in September 2018. Staff training and education sessions were held. The team, with the assistance of an Australian Volunteers International Pharmacist, has helped the NRH staff to develop localized Solomon Islands Oncology Guidelines. Donated equipment and supplies have helped with the initial establishment of the service. A second DFAT Oncology mission visit was made in 2019 followed by two NRH oncology nurses visiting Canberra on observership later that year and support of the Solomon's doctor to pursue postgraduate education in cancer sciences. Ongoing mentorship and support has been maintained. RESULTS The island nation now has a sustainable oncology unit delivering chemotherapy treatments and management of patients with cancer. CONCLUSION A collaborative multidisciplinary team approach by professionals from the high-income country working with colleagues from the low-income nation with coordination of different stakeholders was the key to this successful initiative in improving cancer care.
Introduction The addition of Ibrutinib to R-CHOP in younger pts with DLBCL has efficacy, but significant toxicity limits the ability to complete therapy in pts ≥60 yrs (Younes et al, JCO 2019). We have previously demonstrated the deliverability of Ibrutinib with R-mini-CHOP in 80 pts ≥75yrs with DLBCL with a median Average Relative Total Dose of 97%; 77% of pts received 6 cycles of R-mini-CHOP despite SAEs in 62% (Verner et al, Haematol Oncol 2019). Here we present response rates, Cumulative Illness Rating Scale-Geriatrics (CIRS-G) score, left ventricular ejection fraction (LVEF) and quality of life (QoL) data. Methods Pts received six 21 day cycles of ibrutinib 560mg/d and R-mini-CHOP (Rituximab 375mg/m2, cyclophosphamide 400mg/m2, doxorubicin 25mg/m2, vincristine 1mg on day 1 &prednisone 100mg/d x 5) followed by an additional two 21 day cycles of rituximab + ibrutinib (or high dose methotrexate for CNS prophylaxis). Baseline comorbidities assessed by CIRS-G, end of treatment (EOT) response assessment per Lugano 2014 criteria and QoL (EORTC-QLQ-C30 and EQ-5D-5L visual analogue scores (VAS)) are presented for screening, throughout therapy and 1-month post treatment, with differences assessed using ANOVA. Missing values were not imputed. Results 80 pts were recruited from Nov 2015 to Dec 2018. Median age at registration was 81yrs (75-95); 51% female, 81% stage III/IV and 63% IPI 3-5. The majority of pts (88%; 70/80) had a CIRS-G score of ≥6 (range 4-21), a cut-off shown to be associated with a higher risk of early chemotherapy discontinuation in haematological malignancies (Poisson et al, EHA 2016). Median follow-up was 13.1 months (range 0.2 to 42.6). Treatment discontinuation occurred in 31% (25/80) pts. 23/80 (29%) have died; 14 due to progressive lymphoma, 5 due to infection, 1 intra-abdominal haemorrhage, 1 respiratory failure, 1 cardiac arrest, and 1 MPN/MDS. There was no association between baseline CIRS-G score, and completion of treatment, death or disease response. The overall response rate (ORR) on an intention to treat basis was 57/80 (71%). Eight cycles of treatment were completed by 55/80 (69%) pts, of whom 54 had an EOT PET. Of this population there was an ORR of 93% (50/54), with complete metabolic response (CMR) in 47/54 (87%); partial metabolic response in 4/54 (7%); and progressive metabolic disease in 3/54 (6%). A further 6 pts who discontinued treatment early achieved a CMR (between cycles 3-6) and 1 had stable metabolic disease. Progressive disease prior to cycle 8 occurred in 7/80 pts (9%). Eleven pts had no treatment response assessment, either due to death (n=5), withdrawal of consent (n=3), loss to follow up (n=2), or death prior to commencing chemotherapy. 2/80 (2%) pts had a recorded ≥10% decline in LVEF to <50%. There was no significant difference in LVEF from baseline [mean 65.0% (SD 7.1)] to 3 months post EOT [mean 62.2% (SD 9.9)] p=0.21, in the 44 pts with both assessments available for comparison. QoL outcomes are presented in Figures 1 and 2. QOL, as assessed by two globally accepted tools, improved with treatment in the population completing EOT assessment. Patients' EORTC-QLQ-C30 global health status and emotional functioning improved substantially while maintaining physical and cognitive functioning. There was a significant reduction in nausea, vomiting, pain, insomnia, constipation, and diarrhoea and an improvement in appetite with treatment. Similarly EQ-5D-5L VAS demonstrated that patients maintained mobility and independence with a significant reduction in pain/discomfort and improvement in mood. Conclusions Albeit with considerable toxicity and early mortality, Ibrutinib-R mini-CHOP is a deliverable and effective treatment for most pts ≥75yrs with DLBCL. While longer follow-up is required to assess our primary efficacy endpoint of 2yr overall survival, this promising response and reassuring QoL data highlights the merits of ongoing study to identify deliverable and effective treatments for DLBCL in the very elderly. Disclosures Verner: Janssen-Cilag Pty Ltd: Research Funding. Hawkes:Astra Zeneca: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck Sharpe & Dohme: Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding, Speakers Bureau; Merck KgA: Research Funding; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Speakers Bureau; Mundi pharma: Research Funding; Bristol-Myers Squibb: Research Funding, Speakers Bureau. Lee:Janssen: Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; MSD: Membership on an entity's Board of Directors or advisory committees. Cheah:F. Hoffmann-La Roche Ltd: Honoraria, Research Funding; AbbVie: Research Funding; Celgene: Research Funding; Gilead: Honoraria; Janssen: Honoraria; Acerta: Honoraria; Loxo: Honoraria. Purtill:MSD: Honoraria; Novartis: Honoraria, Other: Travel for speaking and advisory boards; Gilead: Honoraria, Other: Travel for speaking and advisory boards; Janssen: Honoraria. Enjeti:Astellas: Consultancy; Novartis: Consultancy; Abbvie: Consultancy; Bayer and Sanofi: Honoraria, Speakers Bureau; Roche: Honoraria, Speakers Bureau. Curnow:NovoNordisk: Honoraria; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CSL: Honoraria; Mylan Pharmaceuticals: Consultancy; Freeline: Membership on an entity's Board of Directors or advisory committees; Boehringher Ingelheim: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Honoraria; Pfizer/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Butcher:ALLG: Honoraria; Abbvie: Honoraria; Astellas: Honoraria; BMS: Honoraria; Janssen-Cilag Pty Ltd: Honoraria; MSD: Honoraria; Novartis: Honoraria; Roche: Honoraria; Shire: Honoraria; Sandoz: Honoraria. Trotman:Pharmacyclics: Research Funding; Celgene: Research Funding; Janssen: Research Funding; BeiGene: Research Funding; Roche: Research Funding. OffLabel Disclosure: Ibrutinib is not currently approved for use in DLBCL
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