scholarly journals Real-World Practice Patterns in a Nationwide Cohort of Veterans with Waldenström's Macroglobulinemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5270-5270
Author(s):  
Kelli M Rasmussen ◽  
Vikas Patil ◽  
Hsu-Chih Chien ◽  
Deborah Kay Morreall ◽  
Catherine Li ◽  
...  
Keyword(s):  
United States ◽  
Real World ◽  
Research Funding ◽  
Treatment Options ◽  
The United States ◽  
Waldenström’S Macroglobulinemia ◽  
The Real ◽  
Treatment Practices ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Background Waldenström's macroglobulinemia (WM) is a rare indolent cancer. Because of its low incidence, the treatment practices for WM primarily rely on data from phase 2 trials, which often have no consensus as to how to best treat this uncommon disease. The heterogeneity of treatments available can be observed in clinical practice guidelines, which recommend traditional chemotherapies, second-generation proteasome inhibitors, multiagent immunotherapies, and the novel Bruton's tyrosine kinase inhibitor, ibrutinib (IBR). Yet, despite clinical evidence and treatment guidelines recommending multiagent chemoimmunotherapy in first-line (1L) patients with WM, a majority of patients still receive monotherapy, namely chlorambucil in Europe and monotherapy rituximab (R) in the United States. To date, there have been no reports on the real-world treatment practices in 1L of WM since the introduction of IBR. The primary objective of this study is to understand the 1L treatment practices for WM in a nationwide cohort of Veterans treated in the largest integrated healthcare system in the United States, the Veterans Health Administration (VA). Methods Using the VA Cancer Registry System and electronic healthcare records, we identified Veterans diagnosed with WM between January 1, 2006, to December 31, 2018. Treatment regimens were classified in accordance with the National Comprehensive Cancer Network (NCCN) guidelines for WM (versions 1.2006, 2.2013, and 2.2019). Eligible patients were followed until loss to follow-up, death or the end of the study observation period (June 30, 2019). The 1L of treatment was examined; with the start date for 1L being the index date. Patients with a cancer diagnosis other than WM and patients who did not receive 1L treatment were excluded from the study. Results We identified 340 patients who were diagnosed with WM and received a 1L treatment regimen between 2006-2019 in the VA. Median age at diagnosis was 68 years (range: 37-92); 334 (98%) of patients were male. Demographics are further described in Table 1. At diagnosis, the median serum IgM was 3083 mg/dl (range: 10-11500), the median hemoglobin was 11 g/dl (range: 5-17), and the platelet count was 204 k/dl (range: 5-732). A noticeable shift in the adoption of treatments can be observed when comparing treatment practices in patients treated between 2006-2009, 2010-2014, and those treated between 2015-2019. From 2006-2009 the majority of 1L patients received monotherapy with R (23, 37%) or chlorambucil (14, 22%). Between 2010-2014, the majority of patients received monotherapy R (43, 34%), with increasing adoption of bendamustine + R (8, 6%) and bortezomib (27, 21%). Between 2015-2019, IBR became the leading 1L treatment (38, 25%), followed by bendamustine + R (33, 22%), monotherapy R (33, 22%), and bortezomib + R (28, 19%). The estimated survival rate of WM patients treated with 1L was 79% at three-years, 68% at 5-years, and 55% at 7-years. Conclusions Our study is one of the first to examine the real-world treatment practices of WM patients treated with 1L after the approval of novel agent IBR. Our results highlight the heterogeneity of treatment options available for WM patients. We also describe the evolution of treatment choices in 1L over the last decade: from chlorambucil and rituximab monotherapy, to ibrutinib, bendamustine, and bortezomib. Retrospective and/or observational studies examining treatments and outcomes in WM patients should take these shifts in treatment practices into consideration. Given the persistent utilization of monotherapy R as a treatment in 1L, despite the superior efficacy of other treatment options such as ibrutinib, bendamustine and bortezomib regimens, our results indicate the need for continued efforts to educate clinicians about the appropriate treatment options available for this rare disease. Acknowledgments: The study was sponsored by Pharmacyclics Disclosures Sauer: University of Utah and SLC VA Medical Center: Employment. Halwani:Genentech, Inc.: Research Funding; Bristol-Myers Squibb: Research Funding; AbbVie: Research Funding; Pharmacyclics: Research Funding; Immune Design: Research Funding; Amgen: Research Funding; Kyowa Hakko Kirin: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding; Miragen: Research Funding.

Trend and Geographic Variations in the Incidence of Waldenstrom’s Macroglobulinemia in the United States over 17 Years from 1988 to 2004.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5174-5174
Author(s):  
Michael Wang ◽  
Yuhong Zhou ◽  
Haijun Wang ◽  
Qing Yi ◽  
Yanxia Zhang ◽  
...  
Keyword(s):  
United States ◽  
The United States ◽  
Waldenström’S Macroglobulinemia ◽  
Geographic Variations ◽  
Annual Percent Change ◽  
Percent Change ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Adjusted Incidence ◽  
Waldenström's Macroglobulinemia

Abstract Background: Waldenstrom’s Macroglobulinemia (WM) is an uncommon subtype of B cell malignancy. The updated trend of its incidence in the United States has not been reported. Objective: To better understand the incidence and epidemiological features of WM in the United States. Methods: We conducted a population-based incidence study with 1463 patients (pts) with WM identified from the Surveillance, Epidemiology, and End Results (SEER) tumor registries over 17 years. From the SEER data, 78,558 pts of all ages diagnosed with non-Hodgkin’s lymphoma (NHL) were identified between 1988 and 2004 in 9 SEER areas. Of these pts, 1463 had pathologically confirmed WM, accounting for 2% of NHL. The incidence with 95% confidence intervals were generated from SEER*Stat Software and was age-adjusted to the U.S. year 2000 standard population. Annual Percent Change (APC)for the incidence was calculated and considered to be statistically significant if p value was less than 0.05. The crude 1-year survival rate was calculated as the ratio of the number of pts who survived over 1 year and the number of pts diagnosed with WM. Results: Of the1463 pts with WM, median age at diagnosis was 73. Overall incidence rate was 0.37/100,000/year, which increased with age from 0.03 in pts aged <50 to 1.03 in pts aged 60–69 and 2.76 in pts aged 80 or older. The age-adjusted incidence did not change significantly from 0.34 in 1988 compared with 0.36 in 2004. Therefore was no significant Annual Percent Change (0.97%, p>0.05). Incidence of WM was higher in men (0.52) than in women (0.26) (P<0.001). There were substantial geographic variations (p<0.001) in the incidence of WM. The age-adjusted incidence was highest in Seattle (0.49) and lowest in Atlanta (0.19). The incidence was higher in Caucasians (0.40) than in African-Americans (0.17) and other races (0.20). Annual Percentage Change was 1.3% in Caucasians (p<0.05). Conclusion: The overall incidence of Waldenstrom’s Macroglobulinemia did not change significantly from 1988 to 2004, and was significantly higher in male Caucasians. There were substantial geographical variations in the incidence of Waldenstrom’s Macroglobulinemia in the United States.

scholarly journals Global Waldenström's Macroglobulinemia Patient-Derived Data Registry, Whimsical, Highlights Real-World Treatment Outcomes and COVID-19 Data

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1343-1343
Author(s):  
Ibrahim Tohidi-Esfahani ◽  
Andrew Warden ◽  
Elena Malunis ◽  
Peter Liburdi deNardis ◽  
Michelle Postek ◽  
...  
Keyword(s):  
Real World ◽  
Research Funding ◽  
Waldenström’S Macroglobulinemia ◽  
First Line ◽  
Advisory Committees ◽  
Eortc Qlq C30 ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Eortc Qlq ◽  
Waldenström's Macroglobulinemia

Abstract Introduction: WhiMSICAL (Waldenström's Macroglobulinemia Study Involving CArt-wheeL) is the first global Waldenström's Macroglobulinemia (WM) registry capturing patient-derived data to complement scarce clinical trials data in this rare cancer (Tohidi-Esfahani et al, Am J Hematol 2021). The registry was interrogated to identify real-world first line treatment outcomes, quality of life (QoL) and coronavirus disease 2019 (COVID-19) data. Methods: The registry captures data through www.cart-wheel.org, an online rare cancer database, utilizing a tailored questionnaire developed by clinician and patient investigators. WM patients complete consent online, then enter symptom, pathology, treatment, QoL (EORTC QLQ-C30) and COVID-19 data, and can return to update their data on an ongoing basis. Recruitment is driven by social media messaging by the International Waldenström's Macroglobulinemia Foundation investigators. Time to next treatment (TTNT) was assessed from start of first therapy to start of second therapy. Patients without a documented second therapy were censored at the time of last edit to their account. COVID-19 questions included testing, disease severity, vaccination and impact on WM management. Results: As of July 2021, 558 patients from 20 countries have participated in the registry, predominantly from USA (50%), Australia (22%) and the UK (9%). Median age at diagnosis was 61 years (range 24-83) with male predominance (61%). 371 patients documented first-line therapies, with a total of 54 unique therapeutic combinations listed. The seven most common therapies were: bendamustine rituximab (BR, n=94), rituximab monotherapy (Rit., n=52), dexamethasone rituximab cyclophosphamide (DRC, n=33), ibrutinib (n=25), bortezomib dexamethasone rituximab (n=15), rituximab cyclophosphamide vincristine prednisolone (n=14) and chlorambucil (n=10). Comparison of TTNT was limited to the four most common first-line therapies: BR, Rit., DRC, with zanubrutinib (n=5) and ibrutinib plus rituximab (n=2) adding to the first line Bruton tyrosine Kinase inhibitor (BTKi) cohort (n=32). Median ages for the BR, BTKi, DRC and Rit. cohorts were 65, 66, 61 & 65 years, respectively. More patients in the BR cohort listed comorbidities (37%), with BTKi-treated patients reporting the least (19%). Pre-treatment disease burden (median IgM and hemoglobin) trended to being higher in the BR and DRC cohorts (figure 1B-D, IgM p=0.24, Hb p=0.27). At median follow up ranging from 31 to 39 months, BR had superior TTNT to DRC (median: not reached and 104 months, p=0.007, figure 1C) and Rit. (median 26 months, p &lt; 0.0001, figure 1D), and trended to superiority compared to BTKi (median not reached, p=0.08, figure 1B). Median TTNT for the entire cohort (n=371) was 108 months (median follow up 55 months, figure 1A). Assessment of QoL was conducted in all patients (any line of treatment) and compared between patients currently on BTKi therapy (n=64) and patients not exposed to BTKi and treated within the last 12 months (n=84). The expanded BTKi cohort reported better QoL, with mean EORTC QLQ-C30 global scale of 82 ± 14.4 compared to the BTKi-naïve cohort mean 73.4 ± 20.9, p=0.005. This was despite more prior lines of treatment (median 2 [IQR 1-4] compared to 1 [IQR 1-1]; p&lt;0.0001). 324 (58%) patients responded to the COVID-19 questions. 144/324 (44%) had undergone testing for COVID-19, with 11 (8%) returning a positive result; none after vaccination. Median length of symptoms was seven days (range 2-30), with two hospitalized, one requiring intensive care. Both hospitalized patients were on second line ibrutinib. Of 211 responses regarding vaccination status, 15 (7%) were not vaccinated, eight due to availability, five due to personal choice and two due to clinician advice. Regarding impact of the pandemic on their WM management, 5% had treatment schedule disruption and 53% reported reduced face-to-face consultations. Conclusion: The WhiMSICAL registry provides a scientifically robust and ethically approved portal for the patients' voice. The data highlight the real-world efficacy of combination chemoimmunotherapy, particularly first-line BR, and suggest a better QoL with BTKi than other therapies. As this global data platform grows, the breadth of data allows for new insights into WM with patient reported outcomes advancing knowledge and facilitating treatment decisions for clinicians and patients. Figure 1 Figure 1. Disclosures D'Sa: Sanofi: Honoraria; BeiGene: Honoraria, Research Funding; Janssen Cilag: Honoraria, Research Funding. Kersten: Roche: Consultancy, Honoraria, Other: Travel support, Research Funding; Miltenyi Biotec: Consultancy, Honoraria, Other: Travel support; Novartis: Consultancy, Honoraria, Other: Travel support; BMS/Celgene: Consultancy, Honoraria; Takeda: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding; Celgene: Research Funding. Thomas: Acerta Pharma: Research Funding; Ascentage Pharma: Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; X4 Pharma: Research Funding; Genentech: Research Funding. Palomba: Ceramedix: Honoraria; Rheos: Honoraria; Nektar: Honoraria; Priothera: Honoraria; Lygenesis: Honoraria; WindMIL: Honoraria; Wolters Kluwer: Patents & Royalties; Juno: Patents & Royalties; BeiGene: Consultancy; Kite: Consultancy; Magenta: Honoraria; Seres: Honoraria, Other: Stock, Patents & Royalties, Research Funding; PCYC: Consultancy; Notch: Honoraria, Other: Stock; Novartis: Consultancy; Pluto: Honoraria. Olszewski: Acrotech Pharma: Research Funding; Celldex Therapeutics: Research Funding; TG Therapeutics: Research Funding; PrecisionBio: Research Funding; Genentech, Inc.: Research Funding; Genmab: Research Funding. Trotman: PCYC: Research Funding; roche: Research Funding; BMS: Research Funding; TAKEDA: Research Funding; JANSSEN: Research Funding; beigene: Research Funding.

scholarly journals Neither a New Cold War nor a New Peloponnesian War: The Emerging Cyber-narrative Competition at the Heart of Sino-American Relations

2021 ◽  
Vol 21 (2) ◽  
pp. 252-264
Author(s):  
Nicholas Ross Smith ◽  
Ruairidh J. Brown
Keyword(s):  
United States ◽  
Cold War ◽  
Real World ◽  
The United States ◽  
Peloponnesian War ◽  
The Real ◽  
Current State ◽  
Thucydides Trap ◽  
The Relationship ◽  
Industrial Revolutions

There is much pessimism as to the current state of Sino-American relations, especially since the onset of the COVID-19 pandemic in January 2020. Such pessimism has led to some scholars and commentators asserting that the Sino-American relationship is on the cusp of either a new Cold War or, even more alarmingly, something akin to the Peloponnesian War (via a Thucydides Trap) whereby the United States might take pre-emptive measures against China. This article rejects such analogizing and argues that, due to important technological advancements found at the intersection of the digital and fourth industrial revolutions, most of the real competition in the relationship is now occurring in cyberspace, especially with regards to the aim of asserting narratives of truth. Two key narrative battlegrounds that have raged since the onset of the COVID-19 pandemic are examined: where was the origin of the COVID-19 pandemic? and who has had the most successful response to the COVID-19 pandemic?. This article shows that Sino-American competition in cyberspace over asserting their narratives of truth (related to the COVID-19 pandemic) is fierce and unhinged. Part of what is driving this competition is the challenging domestic settings politicians and officials find themselves in both China and the United States, thus, the competing narratives being asserted by both sides are predominately for domestic audiences. However, given that cyberspace connects states with foreign publics more intimately, the international aspect of this competition is also important and could result in further damage to the already fragile Sino-American relationship. Yet, whether this competition will bleed into the real world is far from certain and, because of this, doomsaying via historical analogies should be avoided.

Prospects for Social Reporting in the United States: A Receding Horizon

1987 ◽  
Vol 8 (x) ◽  
pp. 251-261
Author(s):  
Richard C. Rockwell
Keyword(s):  
Social Sciences ◽  
United States ◽  
Real World ◽  
The United States ◽  
Social Reporting ◽  
Social Scientists ◽  
Scientific Advance ◽  
The Real ◽  
Incomplete Model ◽  
The Social

This essay sets forth the thesis that social reporting in the United States has suffered from an excess of modesty among social scientists. This modesty might be traceable to an incomplete model of scientific advance. one that has an aversion to engagement with the real world. The prospects for social reporting in the United States would be brighter if reasonable allowances were to be made for the probable scientific yield of the social reporting enterprise itself. This yield could support and improve not only social reporting but also many unrelated aspects of the social sciences.

The Fissioning of the Modern Family in Utopia- The Real- World Consequences of Political Illusions

2018 ◽  
Vol 1 (1) ◽  
pp. 98-112
Author(s):  
Bryce Christensen
Keyword(s):  
United States ◽  
20Th Century ◽  
Real World ◽  
Family Life ◽  
The United States ◽  
The Real ◽  
The Family ◽  
Modern Family

Since the mid-20th century, the United States-, like many Europeancountries, -has witnessed dramatic changes in family life, resulting inremarkably low rates for marriage and fertility, remarkably high rates fordivorce, cohabitation, and out-of-wedlock births. To understand these changes the article presents, on the example of literature, ideologies, philosophical trends, and intellectual opinions, which in a particularly destructive way influenced the contemporary condition of the family.

A Phase II Trial of the Oral mTOR Inhibitor Everolimus (RAD001) in Relapsed or Refractory Waldenstrom's Macroglobulinemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 587-587
Author(s):  
Irene M Ghobrial ◽  
Morie A Gertz ◽  
Betsy LaPlant ◽  
John Camoriano ◽  
Suzanne R. Hayman ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Waldenström’S Macroglobulinemia ◽  
Advisory Committees ◽  
Overall Response ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

Abstract Abstract 587 Background: The phosphatidylinositol 3-kinase/mammalian target of rapamycin (mTOR) signal transduction pathway controls cell proliferation and survival. Everolimus is an oral agent targeting raptor mTOR (mTORC1). The trial's goal was to determine the anti-tumor activity and safety of single-agent everolimus in patients with relapsed/refractory Waldenstrom's macroglobulinemia (WM). Patients and Methods: Eligible patients had measurable disease (IgM monoclonal protein >1000 mg/dL with >10% marrow involvement or nodal masses >2 cm), a platelet count ≥75,000 × 106/L, a neutrophil count ≥1,000 × 106/L, and a creatinine and bilirubin ≤2x laboratory upper limit of normal. Patients received everolimus 10 mg PO daily and were evaluated monthly. Tumor response was assessed after cycles 2 and 6 and then every 3 cycles until progression. Results: 50 pts were treated. The median age was 63 years (range, 43-85). The overall response rate (CR+PR+MR) was 70% (95% CI: 55-82%), with a PR of 42% and 28% MR. The median duration of response and median progression-free survival (PFS) has not been reached. The estimated PFS at 6 and 12 months is 75% (95%CI: 64-89%) and 62% (95%CI: 48-80%), respectively. Grade 3 or higher related toxicities were observed in 56% of patients. The most common were hematological toxicities with cytopenias. Pulmonary toxicity occurred in 10% of patients. Dose reductions due to toxicity occurred in 52% of patients. Conclusions: Everolimus has high single-agent activity with an overall response rate of 70% and manageable toxicity in patients with relapsed WM, and offers a potential new therapeutic strategy for this patient group. Disclosures: Ghobrial: Millennium: Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Gertz:celgene: Honoraria; millenium: Honoraria, Membership on an entity's Board of Directors or advisory committees. Richardson:Millennium Pharmaceuticals, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Johnson and Johnson: 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; Keryx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Treon:Millennium: Honoraria, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Genentech: Honoraria, Research Funding, Speakers Bureau. Witzig:Novartis: Research Funding.

Molecular Basis of Ibrutinib Resistance in Waldenstrom's Macroglobulinemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 756-756 ◽  
Author(s):  
Lian Xu ◽  
Nicholas Tsakmaklis ◽  
Guang Yang ◽  
Jiaji G Chen ◽  
Xia Liu ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Deep Sequencing ◽  
Molecular Basis ◽  
Research Funding ◽  
Waldenström’S Macroglobulinemia ◽  
Targeted Deep Sequencing ◽  
Pcr Assays ◽  
Waldenstrom's Macroglobulinemia ◽  
Ibrutinib Resistance ◽  
Waldenström's Macroglobulinemia

Abstract Ibrutinib is a small molecule that is approved by the U.S. FDA for the treatment of chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), and Waldenström's Macroglobulinemia (WM). In WM, mutated MYD88 supports the growth and survival of malignant lymphoplasmacytic cells (LPC) through BTK, while CXCR4WHIM mutations promote ibrutinib resistance (Yang et al, Blood 2013; Cao et al, Leukemia 2013). Ibrutinib irreversibly binds to Cys481 on BTK, and blocks its kinase activity. Despite high response rates and durable remissions in WM (Treon et al, NEJM 2015; Dimopoulos et al, ASH 2015), disease progression can occur in WM patients on active ibrutinib therapy. To investigate the molecular basis of ibrutinib resistance in WM, we first focused on BTK mutations at Cys481 that have been associated with ibrutinib resistance in CLL and MCL using Sanger sequencing and nested AS-PCR. To capture the known variants at BTK Cys481, three AS-PCR assays for Cys481SerG>C, Cys481SerT>A, and Cys481ArgT>C were developed with a sensitivity of detecting 0.1% of mutant alleles. Using these assays, we evaluated 8 WM patients who progressed on ibrutinib. Among these 8 patients, 5 had BTK Cys481 mutations: 3 were positive for Cys481SerG>C, and2 were positive for all the three (Cys481SerG>C, Cys481SerT>A, and Cys481ArgT>C) mutations. Cloning/sequencing analysis confirmed co-occurrence of multiple Cys481 mutations within individual WM patients and the presence of mutations at different alleles. Furthermore, targeted deep sequencing (>300X coverage) confirmed all BTK Cys481 mutations, and identified an additional mutation at Cys481 (Cys481TyrG>A) in both patients who were positive for Cys481SerG>C, Cys481SerT>A and Cys481ArgT>C. The estimated allele frequencies by targeted deep sequencing for individual BTK mutations ranged from 1-34%. In contrast, no BTK Cys481 mutations were identified in 100 ibrutinib naive WM patients using the nested AS-PCR assays. Among the 8 WM patients included in this study, all had activating MYD88 mutations, and 4 had CXCR4WHIM mutations. All 4 patients with CXCR4WHIM mutations had BTK Cys481 mutations. We next utilized targeted deep sequencing to expand the mutation analysis to the entire coding regions of the BTK, as well as select genes relevant to BCR and MYD88 signaling. A missense mutation in CARD11 (L878F) was identified in one patient who lacked any BTK Cys481 mutations, while a missense mutation in PLCG2 (Y495H) was found in another patient with a Cys481SerG>C mutation. The findings provide the first reported insights into the molecular mechanisms associated with ibrutinib resistance in WM, and highlight the emergence of multiple BTK mutated clones within individual patients who progress on ibrutinib. Disclosures Castillo: Biogen: Consultancy; Abbvie: Research Funding; Pharmacyclics: Honoraria; Millennium: Research Funding; Otsuka: Consultancy; Janssen: Honoraria. Palomba:Pharmacyclics: Consultancy. Furman:Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Speakers Bureau. Treon:Janssen: Consultancy; Pharmacyclics: Consultancy, Research Funding.

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