Abstract: Sister-of-Mammalian Grainyhead (SOM) is a member of the Grainyhead family of transcription factors. In humans, 3 isoforms are derived from differential first exon usage and alternative splicing and differ only in their N terminal domain. SOM2, the only variant also present in mouse, induces endothelial cell migration and protects against apoptosis. The functions of the human specific isoforms SOM1 and SOM3 have not yet been investigated. Therefore we wanted to elucidate their functions in endothelial cells. Approach and Results— Overexpression of SOM1 in primary human endothelial cells induced migration, phosphorylation of Akt1 and endothelial nitric oxide synthase, and protected against apoptosis, whereas SOM3 had opposite effects; isoform-specific knockdowns confirmed the disparate effects on apoptosis. After reporter assays demonstrated that both are active transcription factors, microarray analyses revealed that they induce different target genes, which could explain the different cellular effects. Overexpression of SOM3 in zebrafish embryos resulted in increased lethality and severe deformations, whereas SOM1 had no deleterious effect. Conclusions— Our data demonstrate that the splice variant–derived isoforms SOM1 and SOM3 induce opposing effects in primary human endothelial cells and in a whole animal model, most likely through the induction of different target genes.

Abstract: The Older people Quality of Life-7 domains (OQoL-7) is a 28-item multidimensional questionnaire developed to measure community-dwelling older people’s QoL. The OQoL-7 assesses both importance of and satisfaction in seven QoL domains (Material resources; Close entourage; Social and cultural life; Esteem and recognition; Health and mobility; Feeling of safety; and Autonomy). This study aimed to investigate concurrent and construct validity of the OQoL-7. A secondary aim was to compare different methods of weighting participants’ ratings of satisfaction according to their individual ratings of importance, as compared to the OQoL-7 total score (unweighted). Methods Data came from the first and second samples of the Lausanne cohort 65+ study, assessed at the same age of 72–77 years in 2011 (N = 1117) and 2016 (N = 1091), respectively. To assess concurrent validity, the OQoL-7 was compared to other measures of the same concept (single QoL item) or related concepts (self-rated health, SF-12). Construct validity was tested by comparing subscores in the seven QoL domains in the presence and absence of two stressful events during the preceding year (financial difficulties and relationship difficulties). The effect of importance weighting was assessed using moderated regression analysis. Results The OQoL-7 total score was significantly associated with the single QoL item (Spearman’s rho 0.46), self-rated health (Spearman’s rho 0.34), SF-12 physical (Spearman’s rho 0.22) and mental (Spearman’s rho 0.28) component scores. Large differences (Cohen’s d  〉  0.8) were observed in the presence or absence of stressful events in the expected QoL domains: “Material resources” in the presence or absence of “Financial difficulties” (Cohen’s d 1.34), and “Close entourage” in the presence or absence of “Relationship difficulties” (Cohen’s d 0.84). Importance weighting resulted in a very small improvement in the prediction of the single QoL item (ΔR 2 0.018). All results were highly consistent across 2011 and 2016 samples. Conclusions The OQoL-7 showed adequate concurrent and construct validity in two samples of older people. In future studies, the decision to use weighted or unweighted scores will depend on the priority given to either optimizing the prediction of QoL or limiting the burden on respondents and the amount of missing data.

Abstract: Background: Acalabrutinib (acala) is a next-generation, highly selective, covalent Bruton tyrosine kinase (BTK) inhibitor approved for patients (pts) with mantle cell lymphoma (MCL) who have received ≥1 prior therapy. The efficacy and safety of acala in relapsed/refractory (R/R) MCL pts was demonstrated in a single-arm phase 2 study (ACE-LY-004; NCT02213926) after a median follow-up of 26 mo (Wang M, et al. Leukemia. 2019;33:2762-6). Here, we present results after an additional year of follow-up. Methods: Adults with MCL and ECOG PS ≤2 who had relapsed or were refractory to 1-5 prior therapies, had no prior BTK/BCL-2 inhibitor exposure, and did not require warfarin/vitamin K antagonists, received oral acala 100 mg twice daily until progressive disease (PD) or toxicity. Overall response rate (ORR; investigator-assessed partial response [PR] or better per Lugano classification), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety were assessed. Minimal residual disease (MRD) was analyzed in formalin-fixed, paraffin-embedded samples and peripheral blood by next-generation sequencing (5x10-6) in pts with available paired samples. Results: 124 pts were included (median age, 68 [range: 42-90] y; ECOG PS ≤1, 93%; bulky lymph nodes ≥10 cm, 8%; extranodal involvement, 72%; intermediate-/high-risk simplified MCL International Prognostic Index score, 44%/17%; median number of prior therapies, 2 [range: 1-5] ; refractory disease, 24%). After a median follow-up of 38.1 mo (range: 0.3-59.5), 24 (19%) pts remain on treatment and an additional 31 pts (55 total; 44%) remain in follow-up for survival. Of the 31 pts in post-acala follow-up, 6 remain PD-free (4 received post-acala treatment: anticancer treatment combinations and allogeneic stem cell transplant [n=3]; radiotherapy [n=1] ). ORR was 81% (95% CI: 74, 88); 48% (95% CI: 39, 57) achieved complete response (CR). Median DOR was 28.6 mo (95% CI: 17.5, 39.1) and the estimated 36-mo DOR rate was 41.9% (95% CI: 31.7, 51.8). Median PFS was 22.0 mo (95% CI: 16.6, 33.3; Figure); estimated 36-mo PFS rate was 37.2% (95% CI: 28.2, 46.1). ORR and PFS were not significantly different between subgroups divided by Ki-67 index (≤50%, & gt;50%); PFS also did not differ significantly by prior treatment regimen (bendamustine/rituximab [BR]-based, non-BR) or prior therapy line (1, 2, ≥3). Median OS was not reached; estimated 36-mo OS rate was 60.5% (95% CI: 51.1, 68.7). Of 30 MRD-evaluable pts, 6 (20%) achieved CR and undetectable MRD (uMRD) and maintained uMRD at last assessment. The adverse event (AE) profile was largely unchanged with an additional year of follow-up. The most frequent AEs (≥20%) of headache (39%), diarrhea (37%), fatigue (30%), cough (23%), myalgia (22%), and nausea (22%) were primarily grade 1/2. Grade 3/4 AEs (≥5%) were neutropenia (11%), anemia (10%), and pneumonia (6%). Overall, 16 pts (13%) had cardiac AEs (11 with prior cardiac risk factors); 3 of the 16 pts had cardiac AEs in the last year of follow-up (grade 3/4: n=2). Overall, 6 pts (5%) had grade 3/4 cardiac AEs (acute coronary syndrome, acute myocardial infarction, complete atrioventricular block, cardiac failure, cardiorespiratory arrest, coronary artery disease, sinus arrest; n=1 each). One pt had grade 3/4 hypertension in the last year (total any grade, n=5 [4%]; total grade 3/4, n=2 [2%] ). Five pts had bleeding AEs in the last year (n=46 [37%] total) including 2 with grade 3/4 AEs of gastrointestinal hemorrhage (n=2 total) and 1 with grade 3/4 subdural hematoma (n=1 total). Three pts had grade 3/4 infections in the last year (n=21 [17%] total). Treatment discontinuation was primarily due to PD (n=74; 60%) and AEs (n=14; 11%). Seventeen AEs led to discontinuation in 14 pts; each AE occurred in only 1 pt. There were 57 deaths (46%), most commonly due to PD (n=38; 31%) or AEs (n=6; 5%); 14 deaths (11%) occurred in the last year of follow-up (PD, n=9; other, n=1; unknown, n=4). There were 6 deaths due to AEs (bilateral pulmonary embolism, critical aortic stenosis, myelodysplastic syndrome, pneumonia, suicide, non-small cell lung cancer); none were related to acala. Conclusion: Extended follow-up demonstrates no emerging safety concerns for acala in R/R MCL pts. After a median of 38.1 mo, 19% of pts remain on acala. Overall, an estimated one-third of pts remain progression free at 36 mo, with median OS not yet reached. These data support long-term use of acala in R/R MCL pts. Disclosures Wang: Dava Oncology: Honoraria; Verastem: Research Funding; Loxo Oncology: Consultancy, Research Funding; Pulse Biosciences: Consultancy; OncLive: Honoraria; Molecular Templates: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Beijing Medical Award Foundation: Honoraria; BioInvent: Research Funding; Acerta Pharma: Research Funding; VelosBio: Research Funding; Targeted Oncology: Honoraria; Lu Daopei Medical Group: Honoraria; OMI: Honoraria, Other: Travel, accommodation, expenses; MoreHealth: Consultancy; Juno: Consultancy, Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Guidepoint Global: Consultancy; Nobel Insights: Consultancy; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; InnoCare: Consultancy; Oncternal: Consultancy, Research Funding. Rule:Celgene: Consultancy; Celltrion: Consultancy; Roche Pharma AG: Consultancy, Research Funding; Janssen Oncology: Consultancy, Research Funding, Speakers Bureau; AstraZeneca: Consultancy. Zinzani:ADC Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics, Inc.: Honoraria, Speakers Bureau; Kirin Kyowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Portola: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celltrion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sandoz: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Servier: Consultancy, Honoraria, 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; Eusapharma: Consultancy, Speakers Bureau; EUSA Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AbbVie: 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; Immune Design: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Goy:Kite, a Gilead Company: Consultancy, Current equity holder in publicly-traded company, Honoraria, Other: leadership role, Research Funding; MD Anderson: Research Funding; Celgene: Honoraria, Research Funding; CALBG: Research Funding; Janssen: Consultancy, Honoraria, Other: leadership role, Research Funding; Hackensack UMC and University of Nebraska: Research Funding; Karyopharm: Research Funding; Xcenda: Consultancy; Regional Cancer Care Associates/OMI: Current Employment; COTA: Consultancy, Current equity holder in publicly-traded company, Other: leadership role; Acerta: Consultancy, Honoraria, Other: leadership role, Research Funding; RCCA/OMI: Current Employment; PracticeUpdate Oncology: Consultancy; Infinity Verastem: Research Funding; AbbVie: Research Funding; Morphosys: Research Funding; Genentech/Roche: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: leadership role, Research Funding; Bayer: Research Funding; Infinity: Research Funding; Constellation: Research Funding. Casasnovas:Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Gilead: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Roche: Consultancy, Honoraria, Other: travel, accomodations, expenses, Research Funding; MSD: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Smith:Ignyta: Research Funding; Genentech: Research Funding; Bayer: Research Funding; AstraZeneca: Research Funding; Merck: Research Funding; De Novo Biopharma: Research Funding; Bristol Meyers Squibb: Research Funding; Ayala: Research Funding; Pharmacyclics: Research Funding; Millenium/Takeda: Consultancy; Acerta Pharma BV: Research Funding; Incyte: Research Funding; Karyopharm: Consultancy; Seattle Genetics: Research Funding; AstraZeneca: Consultancy; Portola: Research Funding; Beigene: Consultancy. Doorduijn:Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company). Morschhauser:Celgene: Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy; Epizyme: Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy; Abbvie: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Panizo:Bristol-Myers Squibb, Kyowa Kirin: Speakers Bureau; Clínica Universidad de Navarra: Current Employment; Janssen, Roche: Membership on an entity's Board of Directors or advisory committees. Shah:Kite/Gilead, Celgene/Juno/BMS, Novartis, Pfizer, Amgen, Spectrum/Acrotech, Precision Biosciences, Beigene, AstraZeneca, Pharmacyclics/Jansen, Adaptive: Honoraria; NCCN: Vice-Chair, Acute Lymphoblastic Leukemia Working Group: Membership on an entity's Board of Directors or advisory committees; Kite/Gilead, Jazz, Incyte: Research Funding; Moffitt Cancer Center: Current Employment; Kite/Gilead, Precision Biosciences, Novartis, AstraZeneca: Other: TRAVEL, ACCOMMODATIONS, EXPENSES. Davies:Celegene, Roche, Kite Pharma, Celegene: Honoraria; Roche: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Roche, Celgene, Kite Pharma, Acerta, Karyopharma, Regeneron, Incyte: Consultancy; Roche, Acerta Pharma, AstraZeneca, Celgene, Gilead, ADC Therapeutics, Gilead: Research Funding. Dupuis:Henri Mondor University Hospital Creteil France: Current Employment. Jacobsen:Merck, Pharmacyclics, F. Hoffmann-LaRoche, Novartis: Research Funding; Takeda: Honoraria; Acerta, AstraZeneca, Merck: Consultancy. Kater:Roche: Research Funding; Celgene: Research Funding; Genentech: Research Funding; Abbvie: Research Funding; Janssen: Research Funding. Le Gouill:Roche Genentech, Janssen-Cilag and Abbvie, Celgene, Jazz pharmaceutical, Gilead-kite, Loxo, Daiichi-Sankyo and Servier: Honoraria; Loxo Oncology at Lilly: Consultancy. Oberic:Roche, Janssen: Consultancy; Roche: Honoraria; Roche, Janssen: Other: Travel, Accommodations, Expenses. Robak:Sandoz: Consultancy, Honoraria; Octapharma: Honoraria; AbbVie: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Janssen: Consultancy, Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; UCB: Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Honoraria, Research Funding; Acerta: Research Funding; Roche: Consultancy, Other: TRAVEL, ACCOMMODATIONS, EXPENSES (paid by any for-profit health care company), Research Funding; Medical University of Lodz: Current Employment; GSK: Research Funding; Novartis: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; UTX-TGR: Research Funding; Takeda: Consultancy; Morphosys: Research Funding; BioGene: Honoraria, Research Funding; Bristol Meyers Squibb: Research Funding; Pfizer: Research Funding; Momenta: Consultancy. Brock:Jazz Pharmaceuticals Inc: Current Employment; Acerta Pharmaceuticals: Ended employment in the past 24 months; Astra Zeneca: Current equity holder in publicly-traded company. Patel:AstraZeneca: Current Employment, Current equity holder in publicly-traded company. Tao:Clindata Insight inc: Ended employment in the past 24 months; Acerta Pharma, LLC: Current Employment.

Abstract: Many measurements at the LHC require efficient identification of heavy-flavour jets, i.e. jets originating from bottom (b) or charm (c) quarks. An overview of the algorithms used to identify c jets is described and a novel method to calibrate them is presented. This new method adjusts the entire distributions of the outputs obtained when the algorithms are applied to jets of different flavours. It is based on an iterative approach exploiting three distinct control regions that are enriched with either b jets, c jets, or light-flavour and gluon jets. Results are presented in the form of correction factors evaluated using proton-proton collision data with an integrated luminosity of 41.5 fb -1 at  √s = 13 TeV, collected by the CMS experiment in 2017. The closure of the method is tested by applying the measured correction factors on simulated data sets and checking the agreement between the adjusted simulation and collision data. Furthermore, a validation is performed by testing the method on pseudodata, which emulate various mismodelling conditions. The calibrated results enable the use of the full distributions of heavy-flavour identification algorithm outputs, e.g. as inputs to machine-learning models. Thus, they are expected to increase the sensitivity of future physics analyses.

Abstract: Introduction: Patients (pts) with relapsed/refractory (R/R) DLBCL after two or more lines of therapy and who are not candidates for stem cell transplantation have limited effective treatment options and a poor prognosis. Selinexor, an oral XPO1 inhibitor, causes nuclear accumulation and activation of tumor suppressor proteins including p53, p21, and IκBα, along with reductions in c-Myc and Bcl-2 oncogenes. In a phase 1 clinical study (NCT01607892), pts with R/R DLBCL treated with selinexor had an overall response rate (ORR) of 32%, with 4 complete responses (CRs, 6%). Based on these findings, a phase 2b open-label study (SADAL) of selinexor in pts with R/R DLBCL not candidates for transplantation was initiated. Methods: Pts with R/R DLBCL were stratified by subtype (GCB or non-GCB). Pts achieving a best response of PR/CR on prior therapy required a 8 week washout before enrolling on trial. The primary objectives included efficacy (ORR and associated DOR) and safety.Pts were initially randomized to 60 or 100 mg of selinexor twice weekly (8 doses) per 28-day cycle. Disease response was assessed by an Independent Central Radiological Review (ICRR), using the Lugano Classification (Cheson, 2014). Results: Preliminary results from the planned interim analysis showed similar ORRs on the 60 and 100 mg doses, but reduced DOR and tolerability at the higher dose; the 100 mg arm was therefore discontinued. 110 pts were enrolled on the 60 mg arm (66 M/ 44 F, median age 67 yrs) with a median of 3 (range 2-5) prior treatment regimens. The most frequently reported treatment related adverse events (AEs) included(all grades, grades 3, 4): nausea (51%, 6%, 0%), fatigue (50%, 10%, 0%), thrombocytopenia (47%, 22%, 15%), anorexia (35%, 2%, 0%), neutropenia (27%, 20%, 0%), and anemia (27%, 12%, 1%). These AEs were managed with dose modifications and/or standard supportive care. At the planned interim analysis (N=32, 60 mg) the ICRR determined ORR was 34.4% (5 CRs and 6 partial responses (PRs)). The median duration of response (DOR) was 8.4 months. ORR was 33.3% in GCB and 35.3% in non-GCB subtypes. The median overall survival (OS) was 9.0 months. Median OS (Figure 1) in pts ≥PR was not reached and was significantly longer vs median OS for pts ≤ stable disease (SD) of 4.1 months (p= 〈 0.001). Conclusion: Single agent oral selinexor is active in pts with R/R DLBCL across both GCB and non-GCB subtypes. Responses were deep with CRs noted on therapy and durable, with some responses 〉 24 months, consistent with significant clinical benefit. Importantly, response to therapy (≥PR) was associated with significant improvement in OS of 9.0 months vs 4.1 months for those with ≤SD. Enrollment completion is expected by September 2018. Full study results (N=130) will be presented, including longer follow up (DOR and OS) of pts from the original interim analysis. Pts enrolled in SADAL represent an unmet medical need population, and selinexor may help address this need. Disclosures Casasnovas: Roche: Consultancy, Research Funding; Merck: Consultancy; Bristol-Meyers Squibb: Consultancy; AbbVie: Consultancy; Takeda: Consultancy; Gilead: Consultancy, Research Funding. Goy:Acerta: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics/J & J: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Hackensack University Medical Center: Employment; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genentech: Research Funding; Seattle Genetics: Research Funding; COTA: Membership on an entity's Board of Directors or advisory committees. Hill:Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Follows:Gilead, Janssen, Roche, Abbvie, Takeda, BMS: Membership on an entity's Board of Directors or advisory committees. Jaeger:Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; AOP Orphan: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Membership on an entity's Board of Directors or advisory committees; Takeda-Millenium: Membership on an entity's Board of Directors or advisory committees; Takeda-Millenium: Membership on an entity's Board of Directors or advisory committees; Infinity: Membership on an entity's Board of Directors or advisory committees; Bioverativ: Membership on an entity's Board of Directors or advisory committees; MSD: Research Funding. Kuruvilla:Gilead: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Karyopharm: Honoraria; Roche: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Princess Margaret Cancer Foundation: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy; Merck: Consultancy, Honoraria; Celgene: Honoraria; Amgen: Honoraria; Lundbeck: Honoraria; Leukemia and Lymphoma Society Canada: Research Funding. Caimi:Kite Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; ADC Therapeutics: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau. Matczak:Karyopharm Therpeutics: Employment. Ma:Karyopharm Therapeutics: Employment. Saint-Martin:Karyopharm Therapeutics: Employment. Shah:Karyopharm Therapeutics: Employment. Kauffman:Karyopharm Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees. Shacham:Karyopharm Therapeutics: Employment, Equity Ownership, Membership on an entity's Board of Directors or advisory committees.