Farooq, Umar

Abstract Activated B cell (ABC) type diffuse large B cell lymphoma (DLBCL), double hit lymphoma (DHL) and double expressor lymphoma (DEL) have poor outcomes to frontline R‐CHOP but impact of these molecular features on outcomes of relapsed/refractory (R/R) disease is not well‐characterized. We evaluated the association of diagnostic cell of origin (COO), double hit and double expressor status with overall survival after first relapse in DLBCL patients who were enrolled into the Molecular Epidemiology Resource (MER) cohort. COO was available from immunohistochemistry (IHC) using Hans criteria or gene expression profiling (GEP) (Nanostring) on the diagnostic FFPE biopsy. Of 373 pts with R/R DLBCL, 278 had COO by IHC: 152 were GCB, 107 were non‐GCB. One hundred and fourty had COO by GEP: 44 were ABC, 65 were GCB and 13 were unclassifiable. Nineteen out of 163 (12%) were DHL; 30 out of 135 (22%) had DEL. COO, either by IHC (2 years OS GCB: 45% [CI 95 : 38–54] vs. non‐GCB: 44% [CI 95 :36–55], p > 0.05) or GEP (2 years OS ABC: 42% [CI 95 : 29–59] vs. GCB: 40% [CI 95 : 30–54], p > 0.05), was not associated with difference in OS. DHL (2 years OS 16 [CI 95 :6–45] vs. 45% [CI 95 : 34–59], p < 0.01) and DEL (2 years OS 33% [CI 95 : 20–56], vs. 50% [CI 95 : 41–60], p < 0.05) had lower OS than non‐DHL and non‐DEL/non‐DHL counterparts, respectively. COO by IHC or GEP was not associated with OS in R/R DLBCL while DHL and DEL were adverse prognostic markers in DLBCL at first relapse.

Abstract An enhanced understanding of the molecular heterogeneity of diffuse large B-cell lymphoma (DLBCL) has opened the door to clinical trials evaluating novel agents with subtype-specific activity. It is an emerging question whether core needle biopsies (CNB) can adequately meet the increasing tissue requirements of these clinical trials. This can potentially lead to selective enrollment of patients who can undergo excisional biopsy (EB). It is also important to know whether patients who can undergo extensive diagnostic work up differ in their disease characteristics and outcomes from those who cannot. In this observational study, we describe the characteristics, outcomes, and adequacy of diagnostic tissue in patients with newly diagnosed DLBCL and primary mediastinal large B-cell lymphoma who underwent EB vs CNB. Of the 1061 patients, 532 (49.8%) underwent EB and 529 (50.1%) underwent CNB. A significantly higher proportion of patients with CNB had advanced stage disease, an international prognostic index of ≥3, and inadequate tissue for molecular analyses. Patients with CNB had significantly worse 5-year event-free survival (67.6% vs 56.9%; hazard ratio [HR], 0.76; confidence interval [CI]95, 0.6-0.9, P &lt; .001) and 5-year overall survival (76.4% vs 69.2%; HR, 0.8; CI95, 0.6-0.9, P &lt; .001). Thus, patients who underwent CNB have poor-risk features and inferior outcomes on frontline chemoimmunotherapy, are more likely to have inadequate tissue for molecular analyses, and might not meet the tissue requirements of biomarker-driven clinical trials. Thus, the increasing tissue requirements of biomarker-driven clinical trials may result in the exclusion of patients with high-risk DLBCL who need novel agents.

Abstract Low-grade B-cell lymphomas other than follicular and small lymphocytic lymphoma (LGBCL) account for 10% of all B-cell non-Hodgkin lymphomas. Despite improvements in survival outcomes for these patients, little is known about cause of death (COD) in the rituximab era. For a better understanding, we studied 822 newly diagnosed patients with marginal zone, lymphoplasmacytic, and unclassifiable low-grade B-cell lymphoma prospectively enrolled in the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource from 2002 to 2015. COD was assigned based on medical record review using a standard protocol. At a median follow-up of 107 months, 219 (27%) patients had died. The incidence of lymphoma-related deaths when pooling across subtypes was lower than non–lymphoma-related deaths (10-year incidence, 8.0%; 95% confidence interval [CI]: 6.2-10.4 vs 13.6%; 95% CI: 11.2-16.6). The incidence of lymphoma-related deaths varied by subtype, ranging from 3.7% at 10 years in extranodal marginal zone lymphoma to 19.3% in lymphoplasmacytic lymphoma/Waldenström macroglobulinemia. Patients with early progression or retreatment events, defined using event-free survival at 24 months from diagnosis, had significantly higher likelihood of lymphoma-related death compared with patients without early events (10-year estimate: 19.1% vs 5.1%, respectively; P &lt; .001), whereas the rates for non–lymphoma-related death were comparable in patients with or without early events (10-year estimates: 11.0% vs 15.3%, respectively). In conclusion, the most common COD in LGBCLs in the first decade after diagnosis was for causes other than lymphoma. Progression or retreatment within the first 2 years of diagnosis was a strong predictor for risk of lymphoma-related death.

PURPOSE: This study assessed the long-term quality of life (QOL) of patients with aggressive lymphoma subtypes treated with autologous hematopoietic cell transplant (autoHCT) compared with those without history of transplant. METHODS: Patient-reported QOL measures were prospectively gathered from patients enrolled in the Iowa/Mayo Specialized Program of Research Excellence Molecular Epidemiology Resource cohort with aggressive lymphoma subtypes. QOL was measured using the Functional Assessment of Cancer Therapy-General (FACT-G), Functional Assessment of Chronic Illness Therapy–Fatigue Scale, State-Trait Anxiety Inventory (STAI), and Profile of Mood States instruments and with a numeric rating scale for overall QOL and spiritual QOL. The autoHCT group and no HCT groups were compared at 3 years (FU3) and 6 years (FU6) after lymphoma diagnosis. RESULTS: In total, 980 patients with lymphoma (106 autoHCT and 874 no HCT) diagnosed between 2002 and 2013 were included for analysis. The mean FACT-G total score was similar in the autoHCT and no HCT groups at FU3 (89.9 v 90.1, P = .64) and also at FU6 (91.5 v 89.6, P = .44). No differences between the autoHCT and no HCT groups were identified in the FACT subscales. The STAI identified lower anxiety in the autoHCT group by mean STAI1 (state) at FU3 (30.1 v 33.4, P < .01) and by mean STAI2 (trait) at FU6 (30.1 v 33.5, P = .02). No other clinically meaningful differences were identified between the two groups using the other QOL instruments. CONCLUSION: Patients remaining in remission at 3 and 6 years after diagnosis had a high level of QOL with no significant differences associated with history of treatment with autoHCT.

Abstract Background: Event-free survival at 24 months (EFS24) is an important clinical endpoint in newly diagnosed diffuse large B-cell lymphoma and follicular lymphoma, and patients who achieve EFS24 with frontline immunochemotherapy have minimal loss of lifetime compared to age- and sex-matched general population. However, the prognostic role of EFS24 in mantle cell lymphoma (MCL) has not been well studied, possibly due to the perception of continued relapse pattern and poor survival outcome of MCL historically. A recent study from our group demonstrated evolving frontline therapy pattern from 2002-2009 ("Era 1") to 2010-2015 ("Era 2") which was associated with improved EFS and overall survival (OS) in Era 2. In the current study, we sought to explore the prognostic role of EFS24 in the two eras. Methods: Patients with newly diagnosed MCL from 9/2002 through 6/2015 were identified from Molecular Epidemiology Resource (MER), a prospective cohort study of the University of Iowa/Mayo Clinic Lymphoma SPORE. OS was defined as time from diagnosis (or the EFS24 defining event where applicable) to death from any cause and was analyzed using the Kaplan-Meier method. Expected OS accounting for age and sex was generated in R by using the general US population as the reference group. Observed versus expected OS was summarized by using standardized mortality ratio (SMR) and 95% confidence intervals (CI) of observed to expected deaths. Cumulative incidence of lymphoma-specific death was analyzed using Gray's test, with deaths from all other causes treated as competing events. Results: A total of 343 patients were included, 175 from Era 1 (median follow-up 13.0 years) and 168 from Era 2 (median follow-up 6.9 years). Age, sex and simplified MIPI score were similar between the 2 groups. Patients diagnosed in Era 2 had better OS, with a 5-year OS of 68.4% vs 59.2% (simplified MIPI-adjusted hazard ratio 0.68, 95% CI 0.50-0.93). Patients diagnosed in both eras had inferior OS compared to the general population, with an SMR of 3.26 (95% CI 2.70-3.89, P&lt;0.001) in Era 1 and 2.63 (95% CI 2.03-3.36, P&lt;0.001) in Era 2. Patients diagnosed in Era 1 who achieved EFS24 (n=98) still had inferior OS compared to the general population, with an SMR of 2.23 (95% CI 1.67-2.92, P&lt;0.001) (Figure 1A). In contrast, for patients diagnosed in Era 2 who achieved EFS24 (n=99), no evidence of OS difference was found compared to the general population, with an SMR of 1.31 (95% CI 0.78-2.07, P=0.31) (Figure 1B). The primary cause of death after diagnosis was lymphoma-related for patients diagnosed in both eras. The 5-year rate of lymphoma-related death was 28.8% in Era 1 and 20.5% in Era 2. In patients who were diagnosed in Era 1 and achieved EFS24, the primary cause of death after achieving EFS24 remained to be lymphoma-related, with a 5-year rate of 19.8% compared to 6.2% for lymphoma-unrelated causes (Figure 1C). In contrast, in patients who were diagnosed in Era 2 and achieved EFS24, the rate of lymphoma-related death was no longer higher than that of lymphoma-unrelated death, with a 5-year rate of 2.1% vs 5.5%, respectively (Figure 1D). In a sensitivity analysis restricted to only patients who received standard frontline immunochemotherapy, similar results were obtained. For example, in patients who achieved EFS24, the SMR compared to the general population was 2.89 (95% CI 2.00-4.04, P&lt;0.001) in Era 1 and 0.89 (95% CI 0.43-1.64, P=0.82) in Era 2. The 5-year rates of deaths due to lymphoma-related vs lymphoma-unrelated causes were 20.7% vs 6.2% in Era 1 and 1.3% vs 4.9% in Era 2. Conclusions: MCL survival outcome has improved for patients first diagnosed in the more recent era (2010-2015, compared to 2002-2009), likely due to improved frontline therapy as well as better salvage treatments (such as lenalidomide and BTK inhibitors). In the more recent treatment era, patients who achieved EFS24 had survival approaching the age- and sex-matched general population. In addition, these patients had a low risk of dying from lymphoma and were more likely to die from other causes. Longer follow-up (e.g., in Era 2) and external validation in other series are necessary to confirm the prognostic role of EFS24. With more efficacious salvage treatment options and likely continued improvement of OS in MCL, EFS24 may become an important clinical endpoint in frontline therapy of MCL. Figure 1 Figure 1. Disclosures Wang: TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; Eli Lilly: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; InnoCare: Research Funding; LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; MorphoSys: Research Funding. Maurer: Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; BMS: Research Funding; Nanostring: Research Funding. Link: Novartis, Jannsen: Research Funding; Genentech/Roche: Consultancy, Research Funding; MEI: Consultancy. Farooq: Kite, a Gilead Company: Honoraria. Paludo: Karyopharm: Research Funding. Witzig: Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding; Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees. Habermann: Seagen: Other: Data Monitoring Committee; Tess Therapeutics: Other: Data Monitoring Committee; Incyte: Other: Scientific Advisory Board; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Cerhan: Regeneron Genetics Center: Other: Research Collaboration; Celgene/BMS: Other: Connect Lymphoma Scientific Steering Committee, Research Funding; NanoString: Research Funding; Genentech: Research Funding. Nowakowski: Celgene, NanoString Technologies, MorphoSys: Research Funding; Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees.

Abstract Introduction: Central nervous system (CNS) relapse is an uncommon but devastating complication occurring in about 2-10% of patients with diffuse large B-cell lymphoma (DLBCL). The CNS-IPI is a validated prognostic tool used to identify patients at high risk of CNS relapse. MYC and BCL2/BCL6 rearrangements (double-hit lymphoma- DHL) and non-GCB (NGCB) cell of origin may be at higher risk of CNS relapse. However, the ability of these molecular data to refine CNS-IPI risk prediction has not been assessed. In this study, we aimed to describe the impact of DHL and NGCB cell of origin in the incidence of CNS relapse in patients with newly diagnosed DLBCL. Methods: A retrospective review was conducted to identify patients with newly diagnosed DLBCL from 01/01/2002 - 06/30/2015 using the University of Iowa/Mayo Clinic Lymphoma Molecular Epidemiology Resource database. Patients with primary CNS lymphoma or with CNS involvement at diagnosis were excluded. All patients received chemoimmunotherapy. Clinical, biological, laboratory and radiological data were abstracted including the occurrence of CNS relapse. CNS IPI risk score categories were defined as low- (≤1) intermediate- (2-3) and high-risk (≥4) as originally described (Schmitz et al, JCO 2016). Cell of origin (COO) classification into GCB and non-GCB subtypes was performed using Hans algorithm and/or NanoString data. Characteristics between groups were compared using Kruskal-Wallis or Chi-squared test as appropriate. Survival analysis was performed using Cox proportional hazards model and the Kaplan Meier method. Statistical analysis was performed using SAS version 9.4M5 and R version 4.0.3. Results: We identified a total of 1,360 patients with newly diagnosed DLBCL. Patients had a median age of 62 years (range 18-93 years), were predominantly male (56%), had a performance status &lt;2 (84%), had stage III/IV disease (61%) and an elevated LDH (56%) at diagnosis. Fluorescent in situ hybridization data was present for 65% of patients. Among patients with available data, DHL and NGCG COO represented 2.8% and 36% of the cohort, respectively. CNS IPI high- and intermediate-risk categories were present in 12.4% and 52% of the patients, respectively. R-CHOP was the most common upfront chemotherapy (n=980, 72%). The median follow-up for the entire cohort was 84.9 months (IQR: 58.9-120.9). Overall, 50 patients (3.6%) had a CNS relapse during the study period. Lymphoma relapsed in the CNS in 3.0% (95% CI:2.1-4.4), 4.7% (95% CI: 3.4-6.3) and 4.9% (95% CI: 3.7-6.6)% of patients with CNS-IPI score of intermediate/high risk at 1, 3 and 5 years following the diagnosis of DLBCL. In patients with low risk CNS-IPI, 1.1% (95% CI: 0.4-2.5), 1.7% (95% CI: 0.9-3.4) and 1.7% (95% CI: 0.9-3.4) had a CNS relapse at 1, 3 and 5 years following DLBC diagnosis. Patients with CNS relapse were more likely to have elevated LDH (76% vs 56%, p=0.008), advanced stage (78% vs 61%, p=0.01), adrenal involvement (8% vs 2.4%, p=0.014) and have a CNS IPI intermediate risk (68% vs 51%), and high risk (16% vs 12.3%, p=0.014) at the time of initial diagnosis compared to patients without CNS relapse. Patients with CNS relapse had similar rates of DHL (4% vs 2.7%, p=0.17) and NGCB cell of origin (42% vs 36.2%, p=0.52) compared to patients without CNS relapse. In the multivariable analysis, the strongest predictors for CNS relapse were CNS IPI high risk (Hazard Ratio [HR]= 3.6, 95%CI= 1.4-9.7) and CNS IPI intermediate risk (HR= 3.15, 95%CI= 1.46-6.81). DHL and NGCB cell of origin were not associated with a significantly higher risk of CNS relapse (HR= 1.79, [95%CI=0.42-7.59] and HR= 1.26, [95%CI=0.62-2.57], respectively). Conclusion: CNS relapse was an uncommon occurrence in patients with DLBCL who were treated with chemoimmunotherapy. CNS IPI intermediate- and high-risk scores remain the strongest predictors of CNS relapse in patients with DLBCL after adjusting to biological high-risk variables including DHL and NGCB cell of origin. Larger studies are required to validate our findings due to the low incidence of CNS relapse in our cohort. Figure 1 Figure 1. Disclosures Farooq: Kite, a Gilead Company: Honoraria. Maurer: Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Morphosys: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Research Funding; Genentech: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding. Witzig: Karyopharm Therapeutics, Celgene/BMS, Incyte, Epizyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm Therapeutics: Research Funding. Habermann: Tess Therapeutics: Other: Data Monitoring Committee; Seagen: Other: Data Monitoring Committee; Incyte: Other: Scientific Advisory Board; Morphosys: Other: Scientific Advisory Board; Loxo Oncology: Other: Scientific Advisory Board; Eli Lilly & Co.,: Other: Scientific Advisor. Novak: Celgene/BMS: Research Funding.

Abstract Background: Axi-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, is approved for the treatment of pts with relapsed/refractory LBCL with ≥ 2 prior systemic therapies. In the 2-year analysis of ZUMA-1 (NCT02348216), the multicenter, single-arm phase 1/2 study evaluating axi-cel in pts with refractory LBCL, the objective response rate (ORR) was 83%, including a complete response (CR) rate of 58%; 39% of pts had ongoing response with a median follow-up of 27.1 months (Locke et al. Lancet Oncol. 2019). EFS is emerging as a robust surrogate endpoint for OS in hematologic malignancies. A recent systematic analysis demonstrated a linear correlation between EFS and OS in pts with diffuse LBCL after first-line immunochemotherapy (Zhu et al. Leukemia. 2020). Here, we report updated survival findings from the phase 2 portion of ZUMA-1 after 4 years of follow-up, including an evaluation of the association of OS with EFS. Methods: Eligible pts had refractory LBCL (diffuse LBCL, primary mediastinal B cell lymphoma, transformed follicular lymphoma). After leukapheresis at enrollment, pts received low-dose conditioning chemotherapy (fludarabine and cyclophosphamide) followed by a target dose of 2×10 6 anti-CD19 CAR T cells/kg (Neelapu et al. N Engl J Med. 2017). The primary endpoint was ORR, with the first response assessment occurring 4 weeks following infusion. Additional endpoints included safety and translational evaluations. An exploratory analysis of OS by EFS at 12 and 24 months was performed. EFS was defined as the time from axi-cel infusion until disease progression, initiation of new lymphoma therapy (excluding stem cell transplant), or death from any cause. Comparisons of OS by EFS outcomes were analyzed via Kaplan-Meier estimates. Results: Of 111 enrolled pts, axi-cel was administered to 101 pts. As of August 11, 2020, median follow-up was 51.1 months. With over 4 years of follow-up, median OS was 25.8 months, and the 4-year OS rate was 44%. Median EFS in pts treated with axi-cel was 5.7 months, with a 12-month EFS rate of 43% (95% CI, 33-52) and a 24-month EFS rate of 38% (95% CI, 28-47). In pts with an EFS event by Month 12 (EFS12; n=57) vs those without EFS12 (n=44), 4-year OS rates were 7% (95% CI, 2-16) vs 91% (95% CI, 78-97), respectively. Among the 17 pts with EFS12 who were alive at Month 12, 13 (76%) died by Month 48, while among the 44 pts alive at Month 12 without EFS12, 4 (9%) died by Month 48. In pts with an EFS event by Month 24 (EFS24; n=62) vs those without EFS24 (n=39), 4-year OS rates were 13% (95% CI, 6-23) vs 92% (95% CI, 78-98), respectively. Among the 12 pts with EFS24 who were alive at Month 24, 4 (33%) died by Month 48, while among the 39 pts alive at Month 24 without EFS24, 3 (8%) died by Month 48. Since the 2-year analysis (Locke et al. Lancet Oncol. 2019), there have been no new safety signals reported, including no new serious adverse events, no axi-cel-related secondary malignancy, and no confirmed cases of replication-competent retrovirus. Overall, 26 pts received subsequent anti-cancer therapy; median time to next therapy was 8.7 months (range, 0.3 - 53.8). Immunoglobulin therapy was administered to 38 (38%) pts. Two pts in axi-cel-induced remission received allogeneic stem cell transplant; 1 pt was in CR and 1 pt was in partial response. Among treated pts, 58 (57%) have died, primarily due to progressive disease (46%; n=46), followed by other reasons (7%; n=7), adverse events (4%; n=4), and secondary malignancy (myelodysplastic syndrome, with onset on Day 574) unrelated to axi-cel (1%; n=1). Among pts without EFS12 and without EFS24, 1 pt each (2% and 3%, respectively) died due to disease progression &gt;24 months following axi-cel infusion; &gt;36 months, 2 pts each (5% for both) died due to disease progression (1 pt each [2% and 3%]) and other reasons (1 pt each [2% and 3%]. One pt (2%) without EFS12 died due to disease progression between 12 and 24 months. Updated findings with ≥5 years of follow-up, including translational correlations, will be presented. Conclusion: In this long-term survival analysis of ZUMA-1 with ≥4 years of follow-up, axi-cel demonstrated longer OS in pts without EFS events at Month 12 and Month 24 vs pts with events at these timepoints. These data support the use of EFS as a surrogate endpoint for long-term OS in refractory LBCL, and the relationship between EFS and 5-year OS will be presented. Disclosures Jacobson: Nkarta: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support; Axis: Speakers Bureau; Pfizer: Consultancy, Honoraria, Other: Travel support, Research Funding; Clinical Care Options: Speakers Bureau; Celgene: Consultancy, Honoraria, Other: Travel support; Precision Biosciences: Consultancy, Honoraria, Other: Travel support; Lonza: Consultancy, Honoraria, Other: Travel support; Novartis Pharmaceuticals Corporation: Consultancy, Honoraria, Other: Travel support; Humanigen: Consultancy, Honoraria, Other: Travel support. Locke: Moffitt Cancer Center: Patents & Royalties: field of cellular immunotherapy; Janssen: Consultancy, Other: Scientific Advisory Role; Gerson Lehrman Group: Consultancy; Novartis: Consultancy, Other, Research Funding; Legend Biotech: Consultancy, Other; Bluebird Bio: Consultancy, Other: Scientific Advisory Role; BMS/Celgene: Consultancy, Other: Scientific Advisory Role; Calibr: Consultancy, Other: Scientific Advisory Role; Cellular Biomedicine Group: Consultancy, Other: Scientific Advisory Role; Iovance Biotherapeutics: Consultancy, Other: Scientific Advisory Role; GammaDelta Therapeutics: Consultancy, Other: Scientific Advisory Role; Emerging Therapy Solutions: Consultancy; Takeda: Consultancy, Other; Wugen: Consultancy, Other; EcoR1: Consultancy; Umoja: Consultancy, Other; Cowen: Consultancy; Kite, a Gilead Company: Consultancy, Other: Scientific Advisory Role, Research Funding; Amgen: Consultancy, Other: Scientific Advisory Role; Allogene Therapeutics: Consultancy, Other: Scientific Advisory Role, Research Funding. Ghobadi: Atara: Consultancy; Amgen: Consultancy, Research Funding; Wugen: Consultancy; Celgene: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding. Miklos: Pharmacyclics, Amgen, Kite, a Gilead Company, Novartis, Roche, Genentech, Becton Dickinson, Isoplexis, Miltenyi, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet, Adaptive Biotechnologies: Research Funding; Adaptive Biotechnologies, Novartis, Juno/Celgene-BMS, Kite, a Gilead Company, Pharmacyclics-AbbVie, Janssen, Pharmacyclics, AlloGene, Precision Bioscience, Miltenyi Biotech, Adicet, Takeda: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Patents & Royalties; Kite, a Gilead Company, Amgen, Atara, Wugen, Celgene, Novartis, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Bioscience, Adicet, Pharmacyclics, Janssen, Takeda, Adaptive Biotechnologies and Miltenyi Biotechnologies: Consultancy. Oluwole: Kite, a Gilead Company: Consultancy, Research Funding; Janssen: Consultancy; Pfizer: Consultancy; Curio Science: Consultancy. Lin: Gamida Cell: Consultancy; Legend: Consultancy; Juno: Consultancy; Takeda: Research Funding; Merck: Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy; Bluebird Bio: Consultancy, Research Funding; Vineti: Consultancy; Sorrento: Consultancy; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding. Hill: Celgene (BMS): Consultancy, Honoraria, Research Funding; Incyte/Morphysis: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Gentenech: Consultancy, Honoraria, Research Funding; Beigene: Consultancy, Honoraria, Research Funding; Karyopharm: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; AstraZenica: Consultancy, Honoraria; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel Support, Research Funding; Epizyme: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Timmerman: Spectrum Pharmaceuticals: Research Funding; Bristol Myers Squibb: Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Bluebird Bio: Current equity holder in publicly-traded company; Marker Therapeutics: Current equity holder in publicly-traded company; Corvus: Current equity holder in publicly-traded company; Genmab: Current equity holder in publicly-traded company; Merck: Research Funding; TG Therapeutics: Current equity holder in publicly-traded company. Deol: Kite, a Gilead Company: Consultancy. Reagan: Seagen: Research Funding; Kite, a Gilead Company: Consultancy; Genentech: Research Funding; Curis: Consultancy. Stiff: Karyopharm: Consultancy, Honoraria; CRISPR Therapeutics: Consultancy, Honoraria; Kite, a Gilead Company: Research Funding; Amgen: Research Funding; Macrogenics: Research Funding; Bristol Myers Squibb: Research Funding; Janssen: Research Funding; Gamida Cell: Research Funding; Seagen: Research Funding; Cellectar: Research Funding; Incyte: Research Funding; BioLineRX: Research Funding; Cellectar: Research Funding; Actinium: Research Funding; MorphoSys: Consultancy, Honoraria. Flinn: Celgene: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; AstraZeneca: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Rhizen Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Loxo: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Agios: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Karyopharm Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forma Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Infinity Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; ArQule: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Calithera Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Verastem: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Unum Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; AbbVie: Consultancy, Other: All Consultancy and Research Funding payments made to Sarah Cannon Research Institute, Research Funding; Kite, a Gilead Company: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Genentech: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; TG Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Roche: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Incyte: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Takeda: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Constellation Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Acerta Pharma: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Novartis: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Gilead Sciences: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Merck: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Seagen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Portola Pharmaceuticals: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; BeiGene: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Juno Therapeutics: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Janssen: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Nurix Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Pfizer: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Forty Seven: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Curis: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Iksuda Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; IGM Biosciences: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; MorphoSys: Consultancy, Other: All consultancy and research funding payments made to Sarah Cannon Research Institute, Research Funding; Great Point Partners: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Teva: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Trillium Therapeutics: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Triphase Research & Development Corp.: Other: All research funding payments made to Sarah Cannon Research Institute, Research Funding; Century Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Hutchison MediPharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Vincerx Pharma: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Sarah Cannon Research Institute: Current Employment; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Yingli Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Seagen: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Servier Pharmaceuticals: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute; Unum Therapeutics: Consultancy, Other: All consultancy payments made to Sarah Cannon Research Institute, Research Funding; Johnson & Johnson: Current holder of individual stocks in a privately-held company; Seattle Genetics: Research Funding. Farooq: Kite, a Gilead Company: Honoraria. Goy: MorphoSys: Honoraria, Other; Bristol Meyers Squibb: Membership on an entity's Board of Directors or advisory committees; OncLive Peer Exchange: Honoraria; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Research Funding; Michael J Hennessey Associates INC: Consultancy; Physicians' Education Resource: Consultancy, Other: Meeting/travel support; Vincerx: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Meyers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie/Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Honoraria; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie/Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Elsevier's Practice Update Oncology, Intellisphere, LLC(Targeted Oncology): Consultancy; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria; Vincerx pharma: Membership on an entity's Board of Directors or advisory committees; Medscape: Consultancy; Xcenda: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; Genentech/Hoffman la Roche: Research Funding; Infinity/Verastem: Research Funding; Janssen: Research Funding; Rosewell Park: Consultancy; LLC(Targeted Oncology): Consultancy; Hoffman la Roche: Consultancy; Xcenda: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Elsevier PracticeUpdate: Oncology: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Genomic Testing Cooperative: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Karyopharm: Research Funding; Phamacyclics: Research Funding; Constellation: Research Funding; COTA (Cancer Outcome Tracking Analysis): Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees, Other: Leadership role; Hackensack Meridian Health, Regional Cancer Care Associates/OMI: Current Employment. Muñoz: Bayer, Kite, a Gilead Company, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seagen, and Janssen, Millennium: Research Funding; Kite, a Gilead Company, Kyowa, Bayer, Pharmacyclics, Janssen, Seagen, Acrotech, Aurobindo, Beigene, Verastem, AstraZeneca, Celgene/Bristol Myers Squibb, Genentech, and Roche: Speakers Bureau; Pharmacyclics, Abbvie, Bayer, Kite, a Gilead Company, Pfizer, Janssen, Juno/Celgene, Bristol Myers Squibb, Kyowa, Alexion, Beigene, Fosun Kite, Innovent, Seagen, Debiopharm, Karyopharm, Genmab, ADC Therapeutics, Epizyme, Beigene, and Servier: Consultancy; Targeted Oncology, OncView, Kyowa, Physicians' Education Resource, and Seagen: Honoraria; OncView: Honoraria; Kyowa Kirin: Honoraria; Physicians' Education Resource: Honoraria. Siddiqi: Oncternal: Research Funding; Kite Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees; Janssen: Speakers Bureau; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; TG Therapeutics: Research Funding. Shen: Atara: Current Employment, Current equity holder in publicly-traded company, Other: Leadership role, Patents & Royalties; Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment, Other: Leadership role, Patents & Royalties. Bot: Kite, a Gilead Company: Current Employment; Gilead Sciences: Consultancy, Current equity holder in publicly-traded company, Other: Travel support. Dong: GliaCure/Tufts: Consultancy, Patents & Royalties; Gilead: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment. Singh: Kite, a Gilead Company: Current Employment. Spooner: Kite, a Gilead Company: Current Employment; Gilead: Current equity holder in publicly-traded company. Karalliyadda: Kite, a Gilead Company: Current Employment; Gilead: Current equity holder in publicly-traded company. Kim: Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment. Zheng: Gilead Sciences: Current equity holder in publicly-traded company; Kite, a Gilead Company: Current Employment. Neelapu: Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene Therapeutics, Cell Medica/Kuur, Incyte, Precision Biosciences, Legend Biotech, Adicet Bio, Calibr, Unum Therapeutics and Bluebird Bio: Honoraria; Kite, a Gilead Company, Merck, Bristol Myers Squibb, Novartis, Celgene, Pfizer, Allogene, Kuur, Incyte, Precision BioSciences, Legend, Adicet Bio, Calibr, and Unum Therapeutics: Other: personal fees; Takeda Pharmaceuticals and related to cell therapy: Patents & Royalties; Kite, a Gilead Company, Bristol Myers Squibb, Merck, Poseida, Cellectis, Celgene, Karus Therapeutics, Unum Therapeutics (Cogent Biosciences), Allogene, Precision BioSciences, Acerta and Adicet Bio: Research Funding.