ALBERT

Description: Introduction: cGVHD remains a leading cause of post-transplant morbidity / mortality, exhibiting features of both autoimmune and fibrotic diseases across multiple organ systems. cGVHD is characterized by an imbalance between effector and regulatory arms of the immune system that results in over production of inflammatory cytokines including IL-17 and IL-21. Moreover, a persistent reduction in the number of regulatory T (Treg) cells limits the ability of the immune system to re-calibrate this pro-inflammatory environment. KD025 is an orally available Rho-associated coiled-coil kinase 2 (ROCK2) selective inhibitor. In vitro data have demonstrated that KD025 (1) attenuates IL-21 and IL-17 secretion in human CD4+ T cells via STAT3, IRF4 and RORγt regulation, and (2) leads to increased percentages of Foxp3+ CD4+ T cells via a STAT5-dependent mechanism and upregulates the suppressive function of human Tregs. These MOA suggest that KD025 modulates immune homeostasis by shifting the Th17/Treg balance towards a Treg phenotype. No studies have examined KD025 effects in patients with dysregulation associated with high Th17 and low Tregs. Methods: KD025-208 enrolled 3 cohorts (C1: 200 mg QD, C2: 200 mg BID, and C3: 400 mg QD) of patients (pts) with cGVHD after 1-3 prior lines of systemic therapy. Treatment is in 28-Day cycles until disease progression or unacceptable toxicity. The primary endpoint is the overall response rate (ORR) (% pts achieving partial response (PR) or complete response (CR)) as per 2014 NIH response criteria. Secondary endpoints include duration of response (DOR) and corticosteroid (CS) dose reductions. Exploratory endpoints include Lee Symptom Scale (LSS) score and pharmacodynamics (PD). Peripheral blood samples were collected from all pts at Cycle 1 Day 1 (C1D1), C2D1, C4D1 and C6D25, and shipped at ambient temperature. PBMC were isolated and kept frozen until analysis. The intracellular expression of IL-17A and FOXP3 on viable CD3+ CD4+ cells was determined by using multicolor flow cytometry. Results: Data as of 6-June-2018 for C1 and C2 are included; C3 data will be available 4Q18. 17 and 16 pts were enrolled in C1 and C2 with median age 52 years, median time from cGVHD diagnosis to KD025 treatment of 19 months, and a median of 3 prior treatment regimens. Median duration of treatment was 37 (C1) and 33 (C2) weeks (wks). KD025 demonstrated an ORR of 65% in C1 and 63% in C2. ORR in key subgroups is shown below. Responses were rapid (76% achieved at first assessment at 8 wks) and durable with 82% (C1) and 50% (C2) of responders sustaining response for ≥20 wks. Responses including CRs were observed across all affected organ systems except lung (mouth, eyes, joints/ fascia, skin, upper GI, lower GI, esophagus, liver). A previously reported lung PR was deemed on review to be IPF with no cGVHD involvement. During treatment with KD025, median CS dose was reduced by 44% (C1) and 26% (C2). 76% and 56% of pts achieved CS dose reductions. 5/33 (15%) pts discontinued CS. 65% (C1) and 50% (C2) achieved a meaningful improvement (≥7 point reduction) in the LSS score, including both responders (67%) and non-responders (42%). KD025 has been well tolerated. AEs reported were generally consistent with those expected in pts with advanced cGVHD treated with CS. Common AEs were increased LFTs (42%), URI (33%), anemia (27%), nausea (24%), diarrhea (24%) and fatigue (21%). Increased LFTs did not lead to treatment discontinuation, commonly occurred prior to KD025 dosing and were often considered attributable to cGVHD. Grade 3+ LFT increases were reported for 6 (18%) pts. 2 pts discontinued treatment due to AEs possibly related to KD025 (headache, diarrhea). SAEs were reported for 11/33 (33%) pts, none considered related to KD025 treatment. There was no apparent increased risk of infection. Exploratory PD analyses of PBMCs across C1 and C2 revealed an early increase in the percentage of CD4+ Treg cells by C2D1 of KD025 treatment with a simultaneous decrease in Th17 cells. The percentage of CD4+ Tregs continued to increase, and the Th17 cells continued to decrease through C4D1 and C6D25. Conclusion: Treatment with KD025 has demonstrated encouraging clinical responses in cGVHD pts with little toxicity. Responses have been clinically meaningful as evidenced by durability, reductions in CS doses and improvement in LSS score. Exploratory PD data indicate treatment with KD025 may modulate immune homeostasis by restoring the Th17/Treg balance. Figure. Figure. Disclosures Jagasia: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Salhotra:Kadmon Corporation, LLC: Consultancy. Bachier:Sanofi: Speakers Bureau; Seattle Genetics: Speakers Bureau. Weisdorf:Seattle Genetics: Consultancy; Pharmacyclics: Consultancy; Equillium: Consultancy; SL Behring: Consultancy; FATE: Consultancy. Green:Kadmon Corporation, LLC: Employment. Schueller:Kadmon Corporation, LLC: Employment. Zanin-Zhorov:Kadmon Corporation, LLC: Employment. Weiss:Kadmon Corporation, LLC: Employment. Eiznhamer:Kadmon Corporation, LLC: Employment. Aggarwal:Kadmon Corporation, LLC: Employment. Blazar:Kadmon Corporation, LLC: Consultancy, Research Funding. Lee:Takeda: Research Funding; Kadmon: Research Funding; Amgen: Consultancy, Research Funding; Mallinckrodt: Honoraria; Incyte: Consultancy; Pfizer: Consultancy; Onyx: Research Funding.

Description: Introduction: cGVHD exhibits both autoimmune and fibrotic features across multiple organ systems. KD025 is an orally available Rho-associated coiled-coil kinase 2 (ROCK2) selective inhibitor that (1) decreases human T cell IL-21 and IL-17 secretion via STAT3, IRF4 and RORγt regulation; (2) increases percentages and function of Foxp3+ T regulatory cells via a STAT5-dependent mechanism; and (3) reverses established cGVHD in 2 distinct preclinical models. KD025 modulates the immune system by shifting the Th17/Treg balance towards homeostasis. Methods: KD025-208 enrolled 3 sequential cohorts (C) (C1: 200 mg QD, C2: 200 mg BID and C3: 400 mg QD) of patients (pts) with cGVHD after 1-3 prior lines of systemic therapy. Treatment is in 28-Day continuous cycles until disease progression or unacceptable toxicity. The primary endpoint is the overall response rate (ORR) as per 2014 NIH response criteria in the mITT population. Additional endpoints include duration of response (DOR), corticosteroid (CS) dose reductions, failure free survival (FFS) and Lee Symptom Scale (LSS) score. Results: 17, 16 and 21 pts were enrolled in C1, C2, and C3 between Sep-2016 and Mar-2018. Data as of 8-Mar-2019 are included, reflecting a median duration of follow up of 112, 97 and 64 weeks (wks), respectively. At enrollment, median age was 52 yrs, median time from cGVHD diagnosis to treatment was 20 mos, and patients had received a median of 2 prior lines of therapy. 71% of patients were refractory to the last line of therapy prior to enrollment. 50% of pts had cGVHD in ≥4 organs. The median duration of treatment was 37, 33 and 39 wks, respectively. As of 30-Jun-2019, 24% of pts had received 〉18 months of KD025 therapy. 14 pts remain on KD025 treatment. Reasons for discontinuation included cGVHD progression (18), pt voluntary withdrawal (7), relapse of underlying disease (5), investigator decision (5), AE (3) and death (2). ORR (95% CI) was 65% (38%, 85%) in C1, 69% (41%, 89%) in C2, and 62% (38%, 82%) in C3, i.e. 65% (51%, 77%) across all 3 cohorts. Responses were achieved across key subgroups with ORRs of 62% (24/39) in pts with ≥2 prior lines of systemic therapy, 70% (19/27) in pts with ≥4 organs involved and 60% (25/42) in pts with severe cGVHD. CRs were observed in all affected organs except lung; PRs were observed in lung. Responses were rapid, and often achieved within 8 wks, although 4/35 responses occurred after 24 wks. Of note, organs with fibrotic manifestations such as lungs, joints and eyes responded after 24 weeks in some pts. Responses were durable, with a Kaplan-Meier (K-M) median DOR of 34 weeks across all cohorts. 57% of responders sustained a response for ≥20 wks. The K-M median DOR was 34 wks in pts with ≥2 prior lines of systemic therapy. FFS at 6, 12, 18 and 24 mos was 76%, 47%, 40% and 33%, respectively. Baseline median CS dose was 0.21 mg/kg/day of prednisone equivalent. During treatment with KD025, the median CS dose was reduced by 50%. 67% of pts reduced CS dose and 20% discontinued CS completely. The median CS dose reduction was 66% in responders and 25% in non-responders. 52% of pts reported a clinically meaningful improvement (≥7-point reduction) in LSS score during treatment with KD025 with a median time to improvement of 9 wks and a duration for responders of 21 wks. 63% of responders and 32% of non-responders reported a meaningful improvement in LSS score. KD025 was well tolerated with a median Relative Dose Intensity of 98%. Dose reductions/interruptions occurred in 21/54 pts; median duration of interruption was 8.5 days (range 3-20). AEs were consistent with those expected in cGVHD pts receiving CS. Common AEs were URI (35%), diarrhea (31%), nausea (31%), fatigue (30%), dyspnea (28%), increased LFTs (24%), and peripheral edema (22%). 63% had a Grade ≥3 AE; the most common was dyspnea (13%).

Description: Donor lymphocyte infusion (DLI) is use for relapse after allogeneic stem cell transplant (ASCT). Immune activation with cytokines maybe an alternative to DLI. We administered Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Interleukin-2 (IL-2) at the time of relapse after ASCT in patients (pts) with hematologic malignancies. Pts. received subcutaneous GM-CSF at 500 mcg/day on days 1–14 and IL-2 at 1 × 106 units/m2/day on days 8–14. Pts. were off immunosuppressive therapy and had no prior history of graft versus host disease (GVHD) at the start of treatment. Twelve pts. received IL-2/GM-CSF for treatment of relapse AML (7), ALL (2), CML (1), MDS (2). Median age was 55 (range 8–66). Stem cell sources included: peripheral blood = 9, bone marrow = 2, umbilical cord blood (UCB) = 1. Donor sources were: match-related sibling = 4 and match-unrelated donor = 8 (UCB=1). Nine pts. had resistant relapse or primary resistant disease at time of ASCT. Median time from transplant to relapse was 4 months (range = 1–14). Two pts. had failed DLI and 5 pts. had received reinduction chemotherapy prior to IL-2/GM-CSF. Eight pts. responded to IL-2/GM-CSF (CR = 7, PR = 1). Two pts. remain disease free at 18 and 26 months post IL-2/ GM-CSF. Six pts. developed GVHD and of these 4 were responders. Two pts. had GM-CSF discontinued due to increase in peripheral blood blasts. No other toxicities related to IL-2/GM-CSF except for mild flu-like symptoms. The table below summarizes quantitative analysis of immune activation. Values represent means +/− standard error at day 0 (first day of GM-CSF), day 8 (prior to start of IL-2) and day 14 (last day of IL-2 and GM-CSF). P-values are based on paired t-test analysis of day 8 versus day 0 and day 14 versus day 0, respectively. Flow cytometric analysis showed an increase in the numbers of T-lymphocytes (CD3) and T-cell subsets (CD3/CD8 and CD3/CD4) as well as an increase in natural killer cells (CD16/56). Although no differences were seen in the number of dendritic cell subsets, DC1/DC2 ratios decreased with the administration of GM-CSF/IL-2. Limited (n= 4) CD4/FoxP3 analysis did not show change in absolute numbers with administration of GM-CSF/IL-2 (data not shown). In conclusion, cytokine therapy with IL-2/GM-CSF is well tolerated and is an alternative to DLI for relapse after ASCT. Flow cytometry analysis demonstrated a quantitative increase in immune effector cells and polarization to DC2. IMMUNE ACTIVATION FLOW CYTOMETRY ASSAYS D0 (Mean +/− SE) D8 (Mean +/− SE) D14 (Mean +/− SE) P-Value (Day7–0) P-Value (Day 14–0) SE=Standard Error; DC = dendritic cells CD3 (K/uL) 309 +/− 117 535 +/− 103 1306 +/− 403 0.034 0.027 CD3/CD8 (K/uL) 94 +/− 42 174 +/− 33 325 +/− 90 0.021 0.029 CD3/CD4 (K/uL) 309 +/− 117 404 +/− 102 977 +/− 310 0.249 0.045 CD16/CD56 (K/uL) 124 +/− 60 404 +/− 110 496 +/− 162 0.029 0.044 CD19 K/uL) 68 +/−39 89 +/− 36 116 +/− 31 0.183 0.044 Total Lymphs (K/uL 488 +/− 167 942 +/− 160 2353 +/− 532 0.016 0.013 CD11(DC1) (K/uL) 97.1 +/− 60.7 46.3 +/− 32.5 32.6 +/− 27.5 0.108 0.101 CD123(DC2) (K/uL) 32.1 +/− 7.3 39.7 +/− 15.9 45.4 +/− 35.8 0.694 0.628 DC1/DC2 2.77 +/− 1.26 0.68 +/− 0.35 0.61 +/− 0.07

Description: Background High-dose post-transplantation cyclophosphamide (PTC) has proven to be a valuable treatment modality for the prevention of graft-versus-host disease (GVHD) after stem cell transplant (SCT). Granulocyte colony stimulating factor (G-CSF) is routinely given after PTC to improve time to engraftment. Historically, based on the Johns Hopkins regimen, G-CSF is given on Day +5 post-SCT. However, this strategy has not been vigorously compared to other dosing strategies. We sought to assess the effect of delayed (Day +10) or omitted administration of G-CSF on various post-SCT outcomes. Methods Allogeneic SCT patients receiving PTC at standard dosing of 50 mg/kg daily on Days +3 and +4 were included in this retrospective analysis. G-CSF was given at the labeled dose of 5 mcg/kg (rounded to nearest vial) on Day +10 for 15 consecutive patients then omitted entirely for ten consecutive patients. These results were compared to historical controls that received G-CSF beginning Day +5 after PTC. All patients received antimicrobial prophylaxis with levofloxacin, acyclovir and posaconazole. The primary outcome was to determine time to engraftment defined, as an absolute neutrophil count ≥500, in each group. A complete list of secondary outcomes is below and includes febrile neutropenia and infection rates, incidence of acute GVHD, as well as survival and relapse rates. Results Forty-eight patients receiving PTC were included in the final analysis. Patient characteristics and outcomes are described in Table 1. There were no significant differences between the three groups with the exception of cells infused (p=0.03). While there was a longer time to ANC engraftment for patients not receiving GCSF after PTC, this was not statistically significant. Acute GVHD and first year outcomes were unable to be determined at this time for patients not receiving GCSF due to this population not reaching these endpoints at time of submission. Conclusion Administration of G-CSF after post transplant cyclophosphamide is not associated with earlier neutrophil engraftment. Secondary endpoints including platelet engraftment, aGVHD, incidence of febrile neutropenia, or infections were similar among all groups. A larger, randomized study is needed to confirm these results. Disclosures Bachier: Sanofi: Speakers Bureau; Seattle Genetics: Speakers Bureau.

Description: Background Chronic Graft-Versus-Host Disease (cGVHD) is a complication of hematopoietic cell transplantation (HCT). While the clinical outcomes of cGVHD are well documented, few studies have assessed its treatment practices in the real-world. The objectives of this study are to quantify the prevalence of cGVHD, to examine provider prescribing patterns, and to evaluate the healthcare cost and resource utilization (HCRU) in a real-world US cGVHD population. Methods This study analyzed de-identified claims from the Medicare FFS 5% sample for beneficiaries enrolled from 2013-2016 and Pharmetrics commercial 2013-2018 databases to identify cGVHD in allogenic HCT patients. cGVHD was identified based on ICD-9/10 diagnosis codes for cGVHD or unspecified GVHD with a first diagnosis 〉180 days post HCT, or subsequent unspecified GVHD diagnosis 〉12 months post index diagnosis. Chronic GVHD prevalence was estimated by calculating age-adjusted prevalence rates within the Medicare and Pharmetrics sample populations and applying rates to the total US patient subpopulations as determined by CMS and Census data. Prevalence estimates were based on the last complete year of both Medicare FFS and Pharmetrics data (2016). Longitudinal and Line of Therapy (LOT) analyses were based on data from 2013-2018. A new LOT was defined as starting with the addition of systemic therapy to a patient's cGVHD regimen, regardless of prior lines of therapy or prior treatment. Treatments that stopped and restarted within 60 days were considered continuous treatment. Healthcare costs were calculated by adding the inpatient, outpatient, and pharmacy insurer and beneficiary paid amounts for the commercially insured population. Total HCRU was assessed using the number of inpatient and outpatient visits following the initial cGVHD diagnosis. Results In 2016, the projected prevalence of cGVHD in the US based on the Medicare FFS and Pharmetrics commercial databases was 14,017 individual patients. Within 3 years post allogeneic HCT, 42% of patients developed cGVHD; 66% of cGVHD patients had a prior diagnosis of acute GVHD. The majority of cGVHD patients received at least one systemic therapy; 71% and 47% of cGVHD patients progressed to a second and third LOT, respectively (Table 1). Of patients that received a second and third LOT, the average time from diagnosis to the second and third LOT was approximately 7 months and 10 months, respectively. Over 80% of cGVHD patients received systemic corticosteroid therapy for the treatment of cGVHD within 12 months post diagnosis, and 41% of cGVHD patients were receiving a corticosteroid within the 30 days prior to diagnosis. Within the 12 months post cGVHD diagnosis, most patients received a corticosteroid or a corticosteroid combination as a first LOT (57%), which decreased slightly as patients progressed to second and third line of therapy (49% and 48%, respectively). A total of 25 unique therapeutic agents and over 150 combinations were used in second and third LOT. While newer agents, such as ibrutinib and ruxolitinib, are continuing to increase in utilization among cGVHD patients, these therapies are only used among 1% (ibrutinib) and 1-3% (ruxolitinib) of patients through their first three lines of therapy in the patients captured in Pharmetrics commercial database through June 2018. In the 12 months post diagnosis, cGVHD patients had an average of 21.0 GVHD-related inpatient and outpatient visits (2.8 inpatient and 18.2 outpatient visits). In 2016 the average total annual cost per commercially insured cGVHD patient was $291,357. Conclusion A significant proportion of allogenic HCT patients continue to develop cGVHD, and despite advances in the understanding of cGVHD, corticosteroids remain the mainstay of therapy. However, most cGVHD patients are not adequately managed with first line corticosteroids, and many patients are cycling through several therapies, likely in part due to lack of efficacy and toxicity associated with currently available treatments. Real-world utilization of systemic therapies is highly variable, particularly for patients who progress beyond the first LOT, which highlights the need for evidence-based treatment approaches. cGVHD is a highly burdensome complication of allogenic HCT, and safer, more effective treatments are needed as many patients are not currently well managed on available therapies. Disclosures Bachier: Viracyte: Consultancy; Kadmon Corporation, LLC: Consultancy; Sanofi: Speakers Bureau. Aggarwal:Kadmon Corporation, LLC: Employment, Equity Ownership. Hennegan:Kadmon Corporation, LLC: Consultancy. Milgroom:Kadmon Corporation, LLC: Consultancy. Francis:Kadmon Corporation, LLC: Consultancy. Rotta:Jazz: Speakers Bureau; Kadmon Corporation, LLC: Consultancy.

Description: Background: To date, CAR T cell therapy has generally been limited to inpatient treatment at university medical centers. However, most patients (pts) in the US with R/R diffuse large B cell lymphoma receive therapy at non-university medical centers where outpatient delivery of cancer therapy is common. Infusion and management of CAR T cell therapies in the outpatient setting may lead to wider utilization in community/non-university centers and improve access. In TRANSCEND NHL 001, lisocabtagene maraleucel (liso-cel), an investigational, anti-CD19, defined composition, 4-1BB, CAR T cell product administered at target doses of CD4+ and CD8+ CAR T cells, demonstrated efficacy as ≥3rd-line therapy in pts with R/R large B cell NHL. With fewer than half of pts developing cytokine release syndrome (CRS) and/or neurological events (NE) and its delayed onset (median 5 and 10 days, respectively; Abramson, ASCO 2018; 7505) outpatient treatment was allowed with hospitalization at the first sign of fever or neurological symptoms. We report on pts with R/R large B cell NHL who were treated with liso-cel in the outpatient setting in TRANSCEND NHL 001 (NCT02631044) and in two phase 2 studies assessing the safety and efficacy of liso-cel, as ≥3rd-line therapy (OUTREACH; NCT03744676) or as therapy for 2nd-line transplant noneligible (TNE) pts (PILOT; NCT03483103). Methods: Eligible pts had R/R large B cell NHL, adequate organ function, and prior systemic chemoimmunotherapy (TRANSCEND and OUTREACH: ≥2 prior lines of therapy and ECOG PS ≤1; PILOT: 1 prior line of therapy and deemed TNE for autologous hematopoietic stem cell transplantation based on ECOG PS, organ function, and/or age). After lymphodepletion with fludarabine/cyclophosphamide, liso-cel was administered at 1 of 3 dose levels (DL) (DL1 = 50 × 106, DL2 = 100 × 106, DL3 = 150 × 106 total CAR+ T cells) in TRANSCEND and at DL2 in OUTREACH and PILOT. All studies allowed outpatient treatment at non-university (OUTREACH) or at both university and non-university medical centers (TRANSCEND, PILOT). Outpatient treatment required pts to have a caregiver for 30 days post-liso-cel infusion, receive safety-monitoring education (recognizing critical adverse events; eg, fever), and to stay within 1 h travel to the site of care. Outpatient treatment was at the discretion of the investigator. All sites had a multidisciplinary CAR T cell therapy team and standard operating procedures for outpatient administration and toxicity monitoring. CRS (Lee criteria, 2014) and NEs (defined as related to liso-cel; CTCAE criteria) were managed in the hospital. Results: At data cutoff, 37 pts across studies had received liso-cel on study Day 1 and were monitored as outpatients, including pts ≥65 yr old and those with high tumor burden. Patient characteristics are shown in the Table. The most frequent grade ≥3 treatment-emergent AEs were cytopenias (neutropenia 43%, anemia 30%, thrombocytopenia 14%). Sixteen pts had any grade CRS and 12 had any grade NE (19 pts had CRS and/or NE). Severe CRS and/or NE occurred in only 2 pts and were reversible (Table). Three pts received tocilizumab and corticosteroids and 4 pts received corticosteroids alone for CRS and/or NE. No pts received tocilizumab alone. Twenty-two of the 37 pts (59%) required hospitalization at any time; all pts were from TRANSCEND or OUTREACH. Three of those pts (8%) were admitted on study Day 3 or earlier, all for CRS; 1 patient required ICU-level care (length of stay, 3 days). Median (range) time to hospitalization post treatment was 5 (2‒22) days and median (range) length of stay was 6 (2‒23) days. Fifteen (41%) of the 37 pts, including all 5 pts from PILOT, were not admitted to hospital in the first 29 days post liso-cel infusion. Across all 3 studies, most pts achieved an objective response, including CR (Table). Median time to peak CAR+ T cell expansion in each study was 10 days (range: 3-21 in TRANSCEND; 7-10 in OUTREACH; 7-10 in PILOT). Conclusions: A subset of pts with R/R large B cell NHL were successfully treated with liso-cel and monitored for CAR T cell-related toxicity in the outpatient setting, including elderly pts and pts with high tumor burden. Severe CRS and NEs occurred with low incidence. The number of early hospitalizations was low, and 41% of pts did not require hospitalization in the first month post liso-cel infusion. Most pts (65%) achieved an objective response. Updated data with longer follow-up will be presented. Disclosures Bachier: Sanofi: Speakers Bureau; Viracyte: Consultancy; Kadmon Corporation, LLC: Consultancy. Palomba:Noble Insights: Consultancy; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Hemedicus: Speakers Bureau; Merck & Co Inc.: Consultancy; Seres Therapeutics: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; STRAXIMM: Membership on an entity's Board of Directors or advisory committees; Kite Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Evelo: Equity Ownership; MSK (IP for Juno and Seres): Patents & Royalties. Abramson:AbbVie Inc, Amgen Inc, Bayer HealthCare Pharmaceuticals, Celgene Corporation, EMD Serono Inc, Genentech, Gilead Sciences Inc, Janssen Biotech Inc, Juno Therapeutics, a Celgene Company, Karyopharm Therapeutics, Kite Pharma Inc, Merck, Novartis, Seattle Gen: Consultancy. Andreadis:Roche: Equity Ownership; Novartis: Research Funding; Celgene: Research Funding; Juno: Research Funding; Pharmacyclics: Research Funding; Merck: Research Funding; Kite: Consultancy; Genentech: Consultancy, Employment; Gilead: Consultancy; Jazz Pharmaceuticals: Consultancy. Sehgal:Juno/Celgene: Research Funding; Kite/Gilead: Research Funding; Merck: Research Funding. Hildebrandt:Juno Therapeutics: Equity Ownership; crispr therapeutics: Equity Ownership; CVS Health: Equity Ownership; Immunomedics: Equity Ownership; IDEXX laboratories: Equity Ownership; Pfizer: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Cellectis: Equity Ownership; Clovis Oncology: Equity Ownership; Aetna: Equity Ownership; Bluebird Bio: Equity Ownership; Celgene: Equity Ownership; Abbvie: Equity Ownership; Cardinal Health: Equity Ownership; Johnson & Johnson: Equity Ownership; Insys Therapeutics: Equity Ownership; Axim Biotechnologies: Equity Ownership; Axim Biotechnologies: Equity Ownership; Novartis: Equity Ownership; Kite Pharma: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: Travel; Sangamo: Equity Ownership; Procter & Gamble: Equity Ownership; Vertex: Equity Ownership; Bristol-Myers-Squibb: Equity Ownership; Bayer: Equity Ownership; Scotts-Miracle: Equity Ownership; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Travel; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; Takeda: Research Funding; Pharmacyclics: Research Funding; Astellas: Other: Travel; Endocyte: Equity Ownership; GW Pharmaceuticals: Equity Ownership; Kite Pharma: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other; Novartis: Equity Ownership. Siddiqi:PCYC: Consultancy, Research Funding, Speakers Bureau; AstraZeneca: Consultancy, Research Funding, Speakers Bureau; Janssen: Speakers Bureau; Seattle Genetics: Speakers Bureau; Kite, A Gilead Company: Research Funding; TG Therapeutics: Research Funding; Celgene: Research Funding; BeiGene: Research Funding; Juno Therapeutics: Consultancy, Other: travel support, Research Funding. Stevens:Astellas: Consultancy. Farazi:Juno Therapeutics/A Celgene Company: Employment. Kostic:Juno Therapeutics, a Celgene Company: Employment. Trede:Celgene Corporation: Employment, Equity Ownership. Wang:Celgene Corporation: Employment. Lymp:Celgene Corporation: Employment, Equity Ownership. Thelen:Celgene Corporation: Employment. Ogasawara:Celgene Corporation: Employment, Equity Ownership. Maloney:Juno Therapeutics: Honoraria, Patents & Royalties: patients pending , Research Funding; Celgene,Kite Pharma: Honoraria, Research Funding; A2 Biotherapeutics: Honoraria, Other: Stock options ; BioLine RX, Gilead,Genentech,Novartis: Honoraria.