ABSTRACT
Background: Patients with lymphoproliferatie diseases (LPD) appear particularly ulnerable to SARS-CoV-2 infection, partly because of the effects of the anti-neoplastic regimens (chemotherapy, signaling pathway inhibitors, and monoclonal antibodies) on the immune system. The real impact of COVID-19 on the life expectancy of patients with different subtypes of lymphoma and targeted treatment is still unknown. Aims: The aim of this study is to describe and analyse the outcome of COVID-19 patients with underlying LPD treated with targeted drugs such as monoclonal antibodies (obinutuzumab, ofatumumab, brentuximab, niolumab or pembrolizumab), BTK inhibitors (ibrutinib, acalabrutinib), PI3K inhibitors (idelalisib), BCL2 inhibitors (enetoclax) and IMIDs, (lenalidomide). Methods: The surey was supported by EPICOVIDEHA registry. Adult patients with baseline CLL or non-Hodgkin Lymphoma (NHL) treated with targeted drugs and laboratory-confirmed COVID-19 diagnosed between January 2020 and January 2022 were selected. Results: The study included 368 patients (CLL n=205, 55.7%;NHL n=163, 44.3%) treated with targeted drugs (Table 1). Median follow-up was 70.5 days (range 19-159). Most used targeted drugs were ITKs (51.1%), anti-CD20 other than rituximab (16%), BCL2 inhibitors (7.3%) and lenalidomide (7.9%). Of note, only 16.0% of the patients were accinated with 2 or more doses of accine at the onset of COVID-19. Pulmonary symptoms were present at diagnosis in 244 patients (66.2%). Seere COVID-19 was obsered in 47.8 % patients while 21.7% were admitted to to intensie care unit (ICU), being 55 (26.8%) CLL patients and 25 (15.3%) NHL patients. More comorbidities were reported in patients with seere-critical COVID-19 compared to those with mild- asymptomatic infection (p=0.002). This difference was releant in patients with chronic heart diseases (p=0.005). Oerall, 134 patients (36.4%) died. Primary cause of death was COVID-19 in 92 patients (68.7%), LPD in 14 patients (10.4%), and a combination of both in 28 patients (20.9%).Mortality was 24.2% (89/368) at day 30 and 34.5%(127/368) at day 200. After a Cox multiariable regression age >75 years (p<0.001, HR 1.030), actie malignancy (p=0.011, HR 1.574) and admission to ICU (p<0.00, HR 4.624) were obsered as risk factors. Surial in patients admitted to ICU was 33.7% (LLC 38.1%, NHL 24%). Mortality rate decreased depending on accination status, being 34.2% in not accinated patients, 15.9-18% with one or two doses, decreasing to 9.7% in patients with booster dose (p<0.001). There was no difference in OS in NLH s CLL patients (p=0.344), nor in ITKs s no ITKs treated patients (p=0.987). Additionally, mortality rate dropped from the first semester 2020 (41.3%) to last semester 2021 (25%). Summary/Conclusion: - Our results confirm that patients with B--mallignancies treatted with targeted drugs hae a high risk off seere infection (47.8%) and mortality (36.4%) from COVID-19. - Pressence of comorbidities,, especially heart disease,, is a risk factor for seere COVIID--19 infection in ourr series. - Age >75 years,, actie mallignancy att COVIID--19 onset and ICU admission were mortality risk factors. - COVIID--19 acination was a protectie factor for mortality,, een iin this popullation wiitth humorall immunity impairment. - The learning cure in the management of the infection throughout the pandemiic and the deelopmentt off COVIID--19 treatments showed benefit in this partticullarlly ullnerablle popullation? (Table Presented).
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Introduction: The UK currently has six meteor camera networks that are coordinated through the UK Fireball Alliance (UKFAll) [1]. Together, these networks currently image much of the UK's night sky. Since its formal establishment in 2020, the UKFAll has organised field searches following two detected fireball events that dropped meteorites in the UK: one at 21:54 (UTC) 28th February 2021 in Gloucestershire, England, and another at 23:45 (UTC) 14th April 2022 in Shropshire, England. The former fireball detection led to the recovery of the Winchcombe CM chondrite, the first UK meteorite in 30 years [2-4], whilst our search for the Shropshire meteorite have not yet located any stones. Here, we report some lessons learned as a citizen-science and academic collaboration, and from engaging with both local and national communities in searching for meteorites in Gloucestershire and Shropshire, UK. Camera Networks: UKFAll includes the UK Meteor Network (UKMON), Network for Meteor Triangulation and Orbit Determination (NEMETODE), the UK Fireball Network (UKFN), the Fireball Recovery and InterPlanetary Observation Network (FRIPON), the Global Meteor Network (GMN), and the AllSky7 network. Orbital calculations and dark flight modelling are a collaborative effort by researchers from the Global Fireball Observatory based at Curtin University, Australia, as well as the University of Western Ontario, Canada, and FRIPON, France. Winchcombe: Since the Winchcombe meteorite fell during a national lockdown, we issued a press release asking residents in Gloucestershire to report possible meteorite finds following the fireball, as opposed to sending a search party immediately. This approach was successful, with the Wilcock family waking to find a pile of dark rocks and powder on their driveway, and having seen the news, collecting the material and contacting the UKMON. Following verification of the meteorite fall, and additional refinement of the strewn field, a small (~15 scientists) search party assembled in Gloucestershire on 4th March 2021. This led to the recovery of the largest 152 g stone at Rushbury House farm on 6th March 2021. Field Experience: Members of UKFAll with meteorite searching experience led small teams of 4 - 8 people. The search was conducted in a unique situation due to COVID. Care was taken to remain socially distanced at all times, which made coordination of the search efforts challenging. Positive engagement with the local community was prioritised from the outset, with team leaders contacting landowners for permission to search and emphasising our safety precautions and risk assessments. News of the meteorite fall spread quickly, and residents were very hospitable and enthusiastic about our activities. The UK countryside is full of "meteorwrongs", and the rural terrain was difficult to search due to long grass, bushes etc. A game was devised to help boost morale - and to see if a meteorite would be found in that field - where a convincing meteorwrong was thrown into each new area by one team member to be found by the search team. During the field search, we also received many enquiries. These were managed by dedicated UKFAll team members, who replied to emails and visited potential meteorite finds in the area. The press interest in the story following the announcement that the meteorite had been found was significant, with journalists soon arriving in Winchcombe. This press release came after the main UKFAll search had ended, and there were many requests from the the media for interviews. Following several busy days, a key lesson learned was to the need to have a designated media liaison for any future press releases. Shropshire: This meteorite search was carried out over six days by ~20 scientists in an agricultural area south of Shrewsbury that included grazing land for sheep, wheat and rapeseed fields, and woodland. Searching in mid-April proved more challenging due to the increased vegetation cover. In order to train more people in meteorite hunting strategy, search line leaders were alternated each day. An initial small team arrived for the first two days to engage with the community. This "recon" was used to assess the terrain, identify key areas, and obtain permissions, and to avoid inundating small communities with search teams without advance notice. Early on, we engaged with a business owner, who helped to spread the word using local social media groups. Within 24 hours, most residents in the strewn field were aware of the meteorite fall and our presence, with many families conducting their own searches of public land. On 18th April 2022, a press release with an approximate strewn field was issued to local journalists. As with Winchcombe, there was significant national media interest, despite no stone being found to date. This helped us to gain access to search areas, as several landowers were aware of the meteorite before we contacted them. [ FROM AUTHOR] Copyright of Meteoritics & Planetary Science is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)
ABSTRACT
AVENuE - Avelumab in the frontline treatment of advanced classic Hodgkin lymphoma - a window study Background Response adapted ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) has become a standard of care in many countries for advanced stage classic Hodgkin Lymphoma (cHL), as investigated in the RATHL study: following 2 cycles of ABVD patients with negative (Deauville 1-3) interim PET (iPET2) proceeded to 4 cycles of AVD;those with positive (Deauville 4-5) iPET2 intensified therapy to escalated bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone (escBEACOPP) or BEACOPP every 14 days. Overall this strategy was associated with a 3-year progression free survival (PFS) of 82.6%, and outcomes for patients with positive iPET2 were disappointing with 3y progression-free survival (PFS) of 67.5%. More intensive treatment such as upfront use of escBEACOPP has been reported to produce higher PFS (89% at 5 years), but it is unclear whether overall survival (OS) is improved. More intensive treatment is, however, associated with higher risk of toxicity. Inhibitors of programmed cell death protein 1 (PD-1) or programmed death-ligand 1 (PD-L1) have established efficacy in relapsed / refractory cHL with response rates of 55-87%. In the front line setting PD-1 inhibitors have a reported complete metabolic response (CMR) rate of 18-37%. Response to PD-L1 inhibitors in the frontline setting has not been explored. Serial serum TARC (thymus and activation-regulated chemokine) is reported to be prognostic in the frontline treatment of cHL and may aid response assessment because PET interpretation with checkpoint inhibitors is often complex. In the context of PD-1 inhibition, PD-1 expression by immunohistochemistry (IHC) and 9p24.1 copy gain by fluorescence in situ hybridisation (FISH) are reported to correlate with response. Methods AVENuE is a Phase II single-arm multicentre study with sites in the UK and Australia assessing the safety and efficacy of 2 cycles (4 doses) of the PD-L1 inhibitor avelumab for untreated high-risk stage II-IV cHL prior to the iPET2 response adapted approach described above. Eligible patients must be 16-60 years, ECOG 0-1, and have adequate organ function. Patients with;compressive symptoms from lymphoma, autoimmune disorders or immunosuppressive treatment within 2 months are excluded. The primary endpoint is the centrally reviewed PET CMR rate to avelumab. Secondary endpoints are: the safety and tolerability of sequential avelumab and combination chemotherapy as assessed by CTCAE v 5.0;the iPET2 CMR rate after avelumab and 2 cycles of ABVD;PFS and OS at one year. Using a single stage A'hern design, target recruitment is 47 patients to give 90% power at a 0.05% one sided alpha to exclude an overall response rate (ORR) to 2 cycles of avelumab of < 20%;an ORR of 40% would be considered worthy of further study. Recruitment has continued during the COVID-19 pandemic. 29 patients have been enrolled. Exploratory endpoints include correlating disease response with baseline PD-1 copy number by FISH and PD-1 expression by IHC. Serial serum TARC is being explored as an aid to response assessment and changes in peripheral blood immune cell subset are being investigated as possible biomarkers of response. Trial funder: Pfizer Ltd in alliance with Merck KGaA Pfizer Ltd is providing funding as part of an Alliance between Pfizer and Merck KGaA Clinical trials.gov NCT03617666 EUDRACT No.: 2018-002227-42 Disclosures: Hawkes: Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel and accommodation expenses, Research Funding, Speakers Bureau;Regeneron: Speakers Bureau;Merck KgA: Research Funding;Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau;Janssen: Speakers Bureau;Merck Sharpe Dohme: Membership on an entity's Board of Directors or advisory committees;Novartis: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Boa d of Directors or advisory committees;Antigene: Membership on an entity's Board of Directors or advisory committees;Bristol Myers Squib/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding;Specialised Therapeutics: Consultancy. Barrington: Bristol Myers Squibb international corporation: Research Funding;Pfizer Inc: Research Funding;Amgen Ltd: Research Funding;Takeda Speakers Bureau: Honoraria. McKay: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees;Gilead: Honoraria, Other: Travel Support;KITE: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Support;Janssen: Honoraria, Other: Travel Support;Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees;BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Iyengar: Janssen: Other: conference support, Speakers Bureau;Abbvie: Other: conference support;Beigene: Membership on an entity's Board of Directors or advisory committees;Gilead: Membership on an entity's Board of Directors or advisory committees, Other: conference support, Speakers Bureau;Takeda: Membership on an entity's Board of Directors or advisory committees, Other: conference support, Speakers Bureau. Radford: Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau;AstraZeneca: Current holder of individual stocks in a privately-held company;ADC Therapeutics: Consultancy, Current holder of individual stocks in a privately-held company, Honoraria, Speakers Bureau;BMS: Honoraria. Shah: Abbvie, Janssen and Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees. Clifton-Hadley: Bristol-Myers Squibb Pharmaceuticals Ltd.: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.;Amgen: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.;Celgene: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.;Merck Sharp and Dohme: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.;Janssen-Cilag: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.;Pfizer: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.;Millennium pharmaceutics inc.: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials. Collins: Beigene: Membership on an entity's Board of Directors or advisory committees;Novartis: Honoraria, Speakers Bureau;Pfizer: Honoraria;Celgene: Research Funding;Amgen: Research Funding;AstraZeneca: Honoraria, Research Funding;ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees;Celleron: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding;Merck Sharp & Dohme: 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, Research Funding, Speakers Bureau;Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel expenses, Speakers Bureau. OffLabel Disclosure: Avelumab prior to frontline chemotherapy in advanced stage classic Hodgkin lymphoma.
ABSTRACT
S53 Figure 1Rates of mortality against cumulative number of antibiotics received per patient during inpatient spell.[Figure omitted. See PDF]ConclusionIn both COVID-19 waves, antibiotic administration correlated to increased inpatient morbidity and mortality. Given a near-linear relationship of mortality and cumulative antibiotic numbers, antimicrobial stewardship is essential, and tapering an appropriate therapy for likely responsible pathogens will yield lower mortality compared to overlapping coverage and inappropriate escalation. We strongly discourage the use of empirical antibiotics without supporting biochemical evidence of bacterial co-infection for possible future COVID-19 waves.ReferenceRussell C, et al. Lancet Microbe. 2021 Jun 2. https://doi.org/10.1016/S2666-5247(21)00090-2
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P91 Table 1(a) Most frequently observed bacterial species (b) Culture type positivity with relation to rates of mortality(a) Bacteria Number isolated (b) Culture Type Number of positives Number of deaths Positivity mortality Enterococcus 67 Urine 104 28 26.9% Escherichia 65 Blood 76 28 36.8% Staphylococcus 64 Skin 40 16 40% Pseudomonas 24 Sputum & BAL 33 20 60.6% Klebsiella 12 Stool 13 5 38.5% Streptococcus 12 Central venous line 8 4 50% ConclusionBacterial infection is observed far more frequently in COVID-19 patients than previously reported and adversely affects morbidity and mortality. Multiple sites of bacterial infection prolongs inpatient stay and increases mortality. Thorough culture collection should be encouraged in COVID-19 patients with biochemical evidence of bacterial infection to identify responsible pathogens and respective antimicrobial sensitivity. Given the higher mortality rates, empirical use of antibiotics in COVID-19 patients without supporting evidence of bacterial infection is strongly discouraged.ReferencesLansbury, et al. J Infect. 2020 Aug;81(2):266–2.Russell C, et al. Lancet Microbe. 2021 Jun 2. https://doi.org/10.1016/S2666-5247(21)00090-2
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P104 Table 1Mortality rate after presentation of COVID-19 by: tumour type, time from cancer diagnosis, cancer stage, progression of disease, and systemic anti-cancer treatment (SACT). Number mortality number mortality% odds ratio Cancer type Solid organ 75 28 37.3 1.32 Lung 18 11 61.1 4.66** Haematological 29 11 37.9 1.47 Time from diagnosis <12 months 55 25 45.5 2.32** >12 months 67 25 37.3 1.25 STAGE AT DIAGNOSIS 4 46 23 50.0 2.82*** 3 26 13 50.0 2.17 2 14 5 35.7 1.22 1 31 8 25.8 0.77 0 5 1 20.0 0.46 disease progression (<3 months BEFORE COVID-19) Yes 38 22 57.9 4.60*** No 84 28 33.3 1.07 SACT (<3 months BEFORE COVID-19) Yes 53 69 34.0 1.49 No 69 32 46.4 1.80** *p<0.05 **p<0.01 ***p<0.001ConclusionAmong patients with cancer and COVID-19, mortality was high and associated with cancer-specific features. There was no evidence cancer patients on systemic anti-cancer treatments possessed higher mortality from COVID-19 disease, which correlates with findings from COVID-19 and cancer registries1. Patients that did not receive SACT within 3 months before COVID-19 and therefore more likely to have palliative treatment did demonstrate high mortality. Larger studies are needed to confirm the risk of mortality and timing of SACT before COVID-19 disease.ReferenceLee AJ, et al. British Journal of Cancer 2021;124:1777–1784.
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P90 Figure 1The association of PCT in COVID-19 and patient morbidity and mortality.[Figure omitted. See PDF]ConclusionsHere, we report the largest single-centre study to date in analysing a UK-based population for procalcitonin in COVID-19. We observed a significant correlation between elevated initial levels of PCT and incidence of ICU admission and mortality within our cohort, thereby demonstrating promise for PCT as an effective prognostic marker. Using a higher cut-off for PCT ≥0.5µg/L increased mortality by almost 50%, but had no effect on morbidity. We suggest that a lower universal cut-off point for PCT should be used for detecting secondary bacterial infections and procalcitonin-guided antimicrobial therapy.ReferencesHu R, et al. International Journal of Antimicrobial Agents 2020;56(2):106051.Vazzana N, et al. Acta Clin Belg. 2020 Sep 23:1–5.
ABSTRACT
Background: Ibrutinib (ibr) is a once-daily Bruton's tyrosine kinase (BTK) inhibitor approved in the US for patients (pts) with mantle cell lymphoma (MCL) who have received ≥1 prior therapy. Venetoclax (ven) is a BCL-2 inhibitor approved for pts with CLL or previously untreated AML. Ibr + ven have shown synergistic antitumor activity in preclinical models and complementary clinical activity in early phase studies (Zhao Br J Haematol 2015;Tam NEJM 2018;Jain NEJM 2019). The ongoing phase 3 SYMPATICO study (PCYC-1143-CA, NCT03112174) evaluates the safety and efficacy of ibr + ven in pts with relapsed/refractory (R/R) MCL. A safety run-in (SRI) was conducted to inform whether a 1-month (mo) ibr lead-in would be implemented for the randomized portion of the study;initial data from the SRI evaluating tumor lysis syndrome (TLS) events and dose-limiting toxicities (DLTs) concluded that the study would proceed with concurrent ibr + ven, with no ibr lead-in (Wang ICML 2019). Updated safety and efficacy from the SRI are presented. Methods: The phase 3 SYMPATICO study is comprised of an open-label SRI and a double-blind randomized period. Key eligibility criteria were pathologically confirmed MCL with measurable disease, 1-5 prior therapies, and no prior treatment with BTK or BCL inhibitors. In the SRI, pts received oral, once-daily 560 mg ibr + ven in a 5-week ramp-up to 400 mg ven. Ibr + ven are dosed concurrently for 2 years;thereafter, ven is discontinued in all pts and ibr is continued until progressive disease (PD) or unacceptable toxicity. The primary endpoint of the SRI was occurrence of TLS events and DLTs. Secondary endpoints included complete response (CR) and partial response (PR) per the 2014 Lugano criteria, progression-free survival (PFS), and duration of response (DOR). Rates of undetectable minimal residual disease (MRD) were assessed in bone marrow and peripheral blood. Efficacy and safety were analyzed by TLS risk (low or high). TP53 mutational status was determined by next-generation sequencing. Results: Twenty-one pts were enrolled in the SRI, with a median time on study of 22 (range, 2-31) mo. The median age was 68 (range, 53-84) years, and the median number of prior therapies was 2 (range, 1-4);6 pts were considered at low risk for TLS and 15 pts were considered at high risk for TLS. All pts had at least 1 lesion >2 cm at baseline;11/21 (52%) had baseline detectable MRD in peripheral blood or bone marrow. Of the 11 pts with available TP53 mutation data, 4 (36%) had mutated TP53. Median time on treatment was 18 (range, <1-28) mo. During the 5-week ven ramp-up, 3 pts had DLTs, and 1 pt at high risk for TLS had a laboratory TLS (Wang ICML 2019);no additional TLS events occurred during follow-up. The most common treatment-emergent adverse events (TEAEs) were diarrhea (n=16 [76%]) and fatigue (n=11 [52%]). Grade 3/4 TEAEs occurred in 17 pts (81%). Four pts (19%) discontinued study drugs because of TEAEs. Two treatment-emergent deaths occurred: 1 from a retroperitoneal hemorrhage unrelated to ibr or ven that was related to disease progression and 1 from COVID-19 in a pt with CR. The overall response rate (ORR) was 81% (17/21) in all pts, with an ORR of 83% (5/6) in the cohort at low risk for TLS and 80% (12/15) in the cohort at high risk for TLS (Figure). Sixty-two percent (13/21) of pts had CR (low risk for TLS, 67% [4/6];high risk for TLS, 60% [9/15]), 19% (4/21) of pts had PR (low risk for TLS, 17% [1/6];high risk for TLS, 20% [3/15]);5% (1/21) of all pts had stable disease, and 10% (2/21) had PD;1 pt was unevaluable. The median DOR has not been reached (95% CI, 17.5 mo-NE). The median PFS per investigator assessment was not reached (95% CI, 13.7 mo-NE);estimated PFS at 18 mo was 75% (95% CI: 50%-89%) (Figure). All 11 pts with detectable MRD at baseline achieved undetectable MRD, including 7 pts who achieved CRs. Conclusions: Ibr + ven is an all-oral, once-daily, chemotherapy-free regimen being studied for treatment of pts with R/R MCL. With a median of 22 mo on study, no new safety signals we e observed;TLS events and DLTs were rare. Ibr + ven had sustained efficacy, with an ORR of 81%, CR rate of 62%, and the median PFS not reached. All MRD-assessable pts achieved undetectable MRD. The ongoing randomized portion of the SYMPATICO study is evaluating the efficacy and safety of ibr + ven compared with ibr + placebo in pts with R/R MCL;additionally, a single-arm, open-label cohort in previously untreated pts, including pts with TP53 mutations, is ongoing. [Formula presented] Disclosures: Tam: AbbVie: Honoraria, Research Funding;Janssen: Honoraria, Research Funding;BeiGene: Honoraria, Research Funding;Pharmacyclics LLC, an AbbVie Company: Honoraria. Ramchandren: Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding;Janssen: Research Funding. Chen: Autolus Therapeutics: Current Employment. Karlin: Sanofi: Honoraria;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees;Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees;Celgene/Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support;AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support;Celgene: Other: Personal fees;GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support, personal fees. Chong: Hutchison Medipharma: Research Funding;Bayer: Research Funding;Pharmacyclics LLC, an AbbVie Company: Research Funding;Servier: Research Funding;Isofol: Research Funding;Merck Serono: Research Funding;Bristol-Myers Squibb: Research Funding. Jurczak: AstraZeneca, Epizyme: Consultancy;BeiGene: Consultancy, Research Funding;Sandoz Novartis: Consultancy;Janssen: Consultancy, Research Funding;Acerta: Consultancy;Loxo: Consultancy;TG Therapeutics, Acerta, Bayer, MeiPharma: Research Funding;Merck: Research Funding;Pharmacyclics LLC, an AbbVie Company,: Research Funding;Roche: Research Funding;Takeda: Research Funding. Bishton: AbbVie: Research Funding;Gilead: Other: Travel/accomodations/expenses, Research Funding;Roche: Other: Travel/accommodations/expenses, Research Funding;Takeda: Other: Travel/accommodations/expenses, Research Funding;Janssen: Consultancy. Collins: Novartis: Consultancy, Honoraria, Speakers Bureau;ADC Therapeutics: Consultancy, Honoraria;Celleron: Consultancy, Honoraria, Research Funding;BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau;Taekda: Consultancy, Honoraria, Other: travel, accommodations, expenses, Speakers Bureau;Amgen: Research Funding;Celgene: Research Funding;MSD: Consultancy, Honoraria, Research Funding;Gilead: Consultancy, Honoraria, Speakers Bureau;Pfizer: Honoraria;Roche: Consultancy, Honoraria, Other: travel, accommodations, expenses, Speakers Bureau;BeiGene: Consultancy. Szafer-Glusman: Pharmacyclics LLC, an AbbVie Company: Current Employment. Lee: AbbVie: Current equity holder in publicly-traded company;Pharmacyclics LLC, an AbbVie Company: Current Employment. Eckert: Pharmacyclics LLC, an AbbVie Company: Current Employment;AbbVie: Current equity holder in publicly-traded company. Neuenburg: Pharmacyclics LLC, an AbbVie Company: Current Employment;AbbVie: Current equity holder in publicly-traded company. Wang: Targeted Oncology: Honoraria;InnoCare: Consultancy;Oncternal: Consultancy, Research Funding;Nobel Insights: Consultancy;Guidepoint Global: Consultancy;Dava Oncology: Honoraria;Acerta Pharma: Research Funding;Verastem: Research Funding;OMI: Honoraria, Other: Travel, accommodation, expenses;Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;Molecular Templates: Re earch Funding;AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding;OncLive: Honoraria;Lu Daopei Medical Group: Honoraria;Beijing Medical Award Foundation: Honoraria;MoreHealth: Consultancy;Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding;Loxo Oncology: Consultancy, Research Funding;Pulse Biosciences: Consultancy;Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding;Juno: Consultancy, Research Funding;VelosBio: Research Funding;BioInvent: Research Funding. OffLabel Disclosure: Ibrutinib in combination with venetoclax is not approved in any indication