Abstract: Diffuse large B cell lymphoma (DLBCL) is an aggressive but potentially curable malignancy; however, cure is highly dependent on the ability to deliver intensive, anthracycline-based chemoimmunotherapy. Advanced age is an important adverse feature in prognostic models, and nearly one third of cases occur in patients older than 75 years. There is no clear accepted standard of care for older patients with DLBCL due to under-representation of this group in randomized clinical trials. R-miniCHOP, a dose attenuated version of standard R-CHOP, is often chosen based on a prospective, single-arm phase II trial which showed a 2-year progression-free survival (PFS) of 47% (Peyrade, 2011), far lower than observed outcomes in patients younger than 80 yrs (Coiffier, 2002). Precise identification of older DLBCL patients who should be considered for curative versus palliative chemoimmunotherapy is difficult at an individual level; the challenge is to avoid both overtreatment with excessive toxicity and undertreatment with inferior outcomes. The FIL (Fondazione Italiana Linfomi; Italian Lymphoma Foundation) has developed an assessment tool accounting for age, comorbidities, and ability to perform activities of daily living (ADLs) and instrumental activities of living (IADLs). The FIL Tool classifies patients as "fit," "unfit," or "frail." When the FIL tool was prospectively applied to 1163 patients, 55% were fit, 28% were unfit, and 18% were frail. Three-year OS for the whole cohort was 65% and was strongly driven by fitness: 3-year OS was 75% for fit patients, 58% for unfit, and 43% for frail; similar outcomes were seen in a validation cohort (Merli F, 2021). However, treatment was not uniformly directed and was up to the treating physician. Epigenetic deregulation is a feature of DLBCL in older patients, and provides a rationale for targeting methylation. Pre-clinical models show that pre-treatment with hypomethylating agents improves the anti-tumor effect of R-CHOP (Clozel T, 2013). This work has led to early clinical studies of the hypomethylating agent azacitidine with R-CHOP in newly diagnosed DLBCL, with promising early efficacy and acceptable toxicity. The availability of oral azacitidine is an appealing additive approach and is agnostic to cell-of-origin. Based upon the need for improved outcomes in older patients and the promise of azacitidine in this setting, the National Clinical Trials Network (NCTN), led by SWOG, developed S1918, a randomized trial comparing R-miniCHOP to R-miniCHOP + oral azacitidine for older patients ( & gt; age 75) with newly diagnosed aggressive B-cell non-Hodgkin lymphomas. This study incorporates the FIL Tool for baseline frailty assessment and a serial comprehensive geriatric assessment (CGA) to evaluate effects of therapy on quality of life and functional status. This is the first randomized study in this population conducted in North America by the NCTN and will enroll a total of 384 eligible patients after a safety run-in phase. All patients will receive pre-phase therapy with vincristine 1mg x 1 and prednisone 60mg/m2 x 7 days (capped at 100mg/day); pre-phase therapy has been shown to improve performance status and decrease early treatment-related mortality (Owens CN, 2015). The primary objective of the phase II component is to determine if oral azacitidine + R-miniCHOP regimen should be tested further (Phase III) against R-miniCHOP alone based on estimates of 1-year progression-free survival (PFS). The primary objective of the phase III component is to compare the OS at 2 years between oral azacitidine + R-miniCHOP and R-miniCHOP alone. Key correlative tests will include circulating tumor DNA (ctDNA) assays at pre-specified timepoints to explore if ctDNA quantity and methylation patterns correlate with response. S1918 has the potential to impact future trial design and to change the standard of care for patients 75 years and older with aggressive lymphoma in a number of ways given its randomized design, incorporation of geriatric assessments, and utilization of ctDNA correlatives. The prospective assessment of frailty, serial comprehensive geriatric assessments, and introduction of epigenetic modulation will hopefully improve outcomes for this population with significant need. Trial registration: ClinicalTrial.gov Identifier NCT04799275 Funding: NIH/NCI/NCTN grants U10CA180888, U10CA180819, U10CA180820, and U10CA180821 Figure 1 Figure 1. Disclosures Brem: Morphosys/Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; BeiGene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics/Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Consultancy; SeaGen: Speakers Bureau; KiTE Pharma: Membership on an entity's Board of Directors or advisory committees. Caimi: Seattle Genetics: Consultancy; Verastem: Consultancy; XaTek: Patents & Royalties: Royalties from patents (wife); Amgen Therapeutics.: Consultancy; Genentech: Research Funding; Kite Pharmaceuticals: Consultancy; ADC Theraputics: Consultancy, Research Funding; TG Therapeutics: Honoraria. Cerchietti: Bristol Myers Squibb: Research Funding; Celgene: Research Funding. Alizadeh: Foresight Diagnostics: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Forty Seven: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; CAPP Medical: Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Cibermed: Consultancy, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company; Roche: Consultancy, Honoraria; Janssen Oncology: Honoraria; Celgene: Consultancy, Research Funding; Gilead: Consultancy; Bristol Myers Squibb: Research Funding. Olin: Amgen: Honoraria; Cellectis: Research Funding; Pfizer: Research Funding; Daiichi Sankyo: Research Funding; Genentech: Research Funding; Abbvie: Honoraria; Actinium: Honoraria; Astellas: Honoraria, Research Funding. Friedberg: Novartis: Other: DSMC ; Bayer: Other: DSMC ; Acerta: Other: DSMC . Smith: Celgene, Genetech, AbbVie: Consultancy; Alexion, AstraZeneca Rare Disease: Other: Study investigator.

Abstract: Background: Burkitt lymphoma (BL) is a highly aggressive B-cell lymphoma that is largely curable with intensive therapy. Previously, a single-center study of 30 patients demonstrated that DA-EPOCH-R based therapy was highly effective in adults with BL (N Engl J Med 2013; 369:1915-1925). We set out to validate these results in a multi-center study and assess if a risk-adapted approach using DA-EPOCH-R is effective. Methods: Patients had newly diagnosed BL, age 18 years or older and HIV negative or positive. Low-risk (LR) patients (normal LDH, ECOG P.S. 0-1, stage I or II disease and a maximum tumor size 〈 7cm) received 3 cycles of DA-EPOCH-R (with no intrathecal prophylaxis) and all other patients (classified as high risk (HR)) received 6 cycles (with IT prophylaxis days 1 and 5 on cycles 3-6). Results: 77 patients were enrolled. Characteristics include median (range) age 45 (19-78) years; male sex 63 (82%); stage III or IV disease 49 (64%); elevated LDH 41 (53%); CNS involvement 7 (10%); HIV positive 20 (26%). Eleven (14%) and 66 (86%) were classified as LR and HR respectively. There were 2 deaths on treatment in the HR arm secondary to infection. Other toxicities were similar to previous reports of DA-EPOCH-R. At a median follow-up time of 25 months, time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were 92% (95% CI: 82.9-96.8%), 87% (95% CI: 76.2-93%) and 88% (95% CI: 77.1-93.8%) respectively for all patients. TTP, PFS and OS were not significantly different for HR versus LR disease, HIV positive versus negative and age over versus under 40y. Conclusions: In a multicenter setting, both LR and HR patients have excellent outcomes with 3 and 6 cycles of therapy respectively. Risk group, HIV status and age are not associated with outcome (see table). Accrual to this study continues (NCT01092182). Table. TTP PFS OS Patients N=77 92% 87% 88% LR HR p 11 66 100% 91% 0.35 100% 85%0.22 100% 86%0.24 HIV - HIV + p 57 20 96% 84% 0.1 88% 84%0.66 90% 83%0.53 Age under 40 Age over 40 p 35 42 94% 91% 0.83 90% 84% 0.45 93% 83%0.24 Figure 1. Figure 1. Disclosures Link: Genentech: Consultancy, Research Funding; Kite Pharma: Research Funding. Kahl:Roche/Genentech: Consultancy; Seattle Genetics: Consultancy; Millennium: Consultancy; Cell Therapeutics: Consultancy; Celgene: Consultancy; Infinity: Consultancy; Pharmacyclics: Consultancy; Juno: Consultancy. Bartlett:Gilead: Consultancy, Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding; Genentech: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Millennium: Research Funding; Colgene: Research Funding; Medimmune: Research Funding; Kite: Research Funding; Insight: Research Funding; Seattle Genetics: Consultancy, Research Funding; MERC: Research Funding; Dynavax: Research Funding; Idera: Research Funding; Portola: Research Funding; Bristol Meyers Squibb: Research Funding; Infinity: Research Funding; LAM Theapeutics: Research Funding.

Abstract: Introduction Adults with Burkitt lymphoma (BL) are at risk for both early toxic death and disease progression. Age is associated with a poor prognosis with highly dose-intensive regimens, but it is unclear if this is driven by disease biology or treatment intolerance. We previously reported that survival for adult BL patients treated with DA-EPOCH-R were poorest with CNS, bone marrow (BM) and/or peripheral blood (PB) involvement, but age was not prognostic (Roschewski et al J Clin Oncol 2020). A retrospective study of patients treated with standard regimens outside of clinical trials identified the Burkitt Lymphoma International Prognostic Index (BL-IPI) which stratified patients into risk categories based on 4 variables: age ≥40y, ECOG ≥2, serum LDH & gt;3x ULN, and CNS involvement (Olszewski J Clin Oncol 2021). We analyzed the prognostic utility of BL-IPI to predict time to progression (TTP) and event-free survival (EFS) for adult patients with BL treated on a prospective multicenter study of risk-adapted DA-EPOCH-R. Methods NCI 9177 was a multicenter study that included pts ≥ age 18 with any HIV status. Treatment was risk-adapted based on LDH, ECOG status, stage, and largest tumor lesion. Low-risk patients received 3 cycles of DA-EPOCH-RR and high-risk patients received 6 cycles of DA-EPOCH-R with either IT chemo prophylaxis or extended IT treatment for active CNS disease. Event-free survival (EFS) was calculated from study entry until progression, last documentation of active disease, death, or last follow-up. Time to progression (TTP) was calculated from study entry until date of progression. Kaplan-Meier estimation and log-tank tests were used to determine the prognostic utility of the BL-IPI including individual factors. Receiver operating characteristic curves were plotted to determine the c-index which measures the predictive ability of a survival model. Results 113 patients were enrolled including 31 (27%) low-risk, 55 (49%) intermediate-risk, and 27 (24%) high-risk by BL-IPI. With a median follow up of living patients of 3.3y, the 5-year TTP for pts with high-risk BL-IPI was 78.3% (95% CI: 55-90) compared to 95.2% (95% CI: 88-98)(p=0.022) for pts with low/intermediate IPI (Figure 1A). Pts with high-risk BL-IPI had a lower 5-year EFS of 66.7% (95% CI: 46-81) compared to 94.2% (95% CI: 83-98) for intermediate-risk and 83.6% (95% CI: 65-93) for low-risk, respectively (p=0.004)(Table 1). Pts aged ≥40y had a similar 5-year TTP and EFS of 93.6% (95% CI: 84-98) versus 88.4% (95% CI: 74-95)(p=0.32) and 86.7% (95% CI: 76-93) versus 81.1% (95% CI: 66-90)(p=0.50) compared to pts under 40y. Pts with ECOG PS ≥2 had a worse 5-year TTP and EFS of 76.5% (95% CI: 49-90) versus 94.4% (95% CI: 87-98)(p=0.01) and 61.9% (95% CI: 38-79) versus 89.8% (95% CI: 81-95)(p=0.0004) compared to pts with ECOG PS & lt;2. Pts with serum LDH 3x ULN also had worse 5-year TTP and EFS of 77.3% (95% CI: 54-90) versus 95.2% (95% CI: 88-98)(p=0.008) and 65.4% (95% CI: 44-80) versus 90.4% (95% CI: 82-95)(p=0.001) compared to pts without serum LDH & gt; 3x ULN. Pts with CNS involvement had worse 5-year TTP and EFS of 62.5% (95% CI: 23-86) versus 93.9% (95% CI: 87-97)(p=0.002) and 45.5% (95% CI: 17-71) versus 88.8% (95% CI: 81-94)(p=0.0001) compared to pts without CNS involvement. Nineteen (70%) pts high-risk by BL-IPI had CNS/BM/PB involvement while 8 (30%) had no CNS/BM/PB involvement. Ten (12%) pts with low/intermediate-risk by BL-IPI had CNS/BM/PB involvement and 76 (88%) had no CNS/BM/PB involvement. Pts without involvement of CNS/BM/PB had an excellent prognosis across BL-IPI groups with 5-year TTP of 97.3% (95% CI: 90-99) for low/intermediate-risk by BL-IPI and 100% for high-risk by BL-IPI. Patient with CNS/BM/PB involvement had 5-year TTP of 80.0% (95% CI: 41-95) for low/intermediate-risk by BL-IPI and 66.7% (95% CI: 38-85) for high-risk by BL-IPI (global p=0.006)(Figure 1B). Compared to BL-IPI (C-index 0.62 p=0.13), CNS/BM/PB involvement had better discrimination between prognostic groups (C-index 0.76, p=0.0005). Conclusion Patients with low-or intermediate risk BL-IPI scores had an excellent 5-year TTP and EFS of 95% and 94% in NCI 9177. Age is not prognostic with DA-EPOCH-R but CNS/BM/PB involvement is prognostic across BL-IPI groups. Future studies in adults with BL should focus on high-risk disease including younger patients. Figure 1 Figure 1. Disclosures Dunleavy: Gebmab: Honoraria; Beigene: Honoraria; Morphosys: Honoraria; Bayer: Honoraria; Pharmacyclics: Honoraria; Genetech: Honoraria; Idec: Honoraria. Abramson: C4 Therapeutics: Consultancy; Allogene Therapeutics: Consultancy; Kymera: Consultancy; Bluebird Bio: Consultancy; BeiGene: Consultancy; Incyte Corporation: Consultancy; Astra-Zeneca: Consultancy; Novartis: Consultancy; Kite Pharma: Consultancy; Genmab: Consultancy; EMD Serono: Consultancy; Bristol-Myers Squibb Company: Consultancy, Research Funding; Morphosys: Consultancy; Seagen Inc.: Research Funding; AbbVie: Consultancy; Karyopharm: Consultancy; Genentech: Consultancy. Link: MEI: Consultancy; Genentech/Roche: Consultancy, Research Funding; Novartis, Jannsen: Research Funding. Friedberg: Novartis: Other: DSMC ; Acerta: Other: DSMC ; Bayer: Other: DSMC . Kahl: AbbVie, Adaptive, ADCT, AstraZeneca, Bayer, BeiGene, Bristol-Myers Squibb, Celgene, Genentech, Incyte, Janssen, Karyopharm, Kite, MEI, Pharmacyclics, Roche, TG Therapeutics, and Teva: Consultancy; AbbVie, Acerta, ADCT, AstraZeneca, BeiGene, Genentech: Research Funding. Bartlett: Pharmacyclics: Research Funding; Millennium: Research Funding; Merck: Research Funding; Kite, a Gilead Company: Research Funding; Janssen: Research Funding; Genentech: Research Funding; Forty Seven: Research Funding; Celgene: Research Funding; Bristol Myers Squibb: Research Funding; Autolus: Research Funding; Seagen: Consultancy, Research Funding; Roche/Genentech: Consultancy; ADC Therapeutics: Consultancy, Research Funding. Noy: Epizyme: Consultancy; Rafael Parhma: Research Funding; Morphosys: Consultancy; Targeted Oncology: Consultancy; Medscape: Consultancy; Pharmacyclics: Consultancy, Research Funding; Janssen: Consultancy, Honoraria.

Abstract: Background: Standard first-line treatment for patients diagnosed with diffuse large B-cell lymphoma (DLBCL) is the R-CHOP regimen. Despite numerous efforts to improve on this regimen, in all comers and specifically in those with activated B-cell (ABC)-type DLBCL, results from large randomized studies have failed to show a significant clinical advantage above this standard. Recently, 2 large clinical trials in previously untreated DLBCL evaluated the combination of lenalidomide/R-CHOP (R2-CHOP) vs standard R-CHOP and demonstrated discordant results. We analyzed data from these trials to identify differences that may have impacted the disparate trial outcomes while identifying patient characteristics associated with benefit from the addition of lenalidomide across the trials. Methods: The 2 trials included in this evaluation are ROBUST, an international, randomized, double-blinded, placebo-controlled, phase III study of R2-CHOP vs placebo/R-CHOP, and the Intergroup ECOG-ACRIN 1412 (E1412) trial, a US-only, randomized, open-label, phase II study of R2-CHOP vs R-CHOP. Additional key study design differences included dosing, and subtype timing and inclusion (both studies used gene expression profiling [GEP] by NanoString). R-CHOP dosing differed only for prednisone, which was a flat 100 mg dose, d1-5 in ROBUST and 100 mg/m2, d1-5 in E1412. The lenalidomide dose and schedule varied between studies: 15 mg/d, d1-14/21 for ROBUST (210 mg/cycle) and 25 mg/d, d1-10/21 (250 mg/cycle) for E1412. ROBUST enrolled only patients prospectively identified with the ABC subtype, whereas E1412 enrolled all otherwise eligible patients and retrospectively evaluated for ABC-type with prespecified ABC-type accrual and power parameters. Both studies enrolled patients with IPI status ≥ 2, ECOG PS 0-2, and Ann Arbor stage II-IV (E1412 stage II with mass 〉 10 cm). The primary endpoint in both was progression-free survival (PFS; central review for ROBUST and investigator-assessed for E1412). Secondary endpoints included event-free survival (EFS; key for ROBUST), overall and complete response rates, overall survival (OS), and safety. Results: ROBUST enrolled 570 ABC patients and E1412 enrolled 280 GCB, ABC, and unclassified DLBCL patients. Patient profiles in both studies (ROBUST [ABC]/E1412 [all COO] ) were similar in terms of median ages (65 y/66 y), male sex (58%/61%), and ECOG PS 1-2 (55%/63%). Patients in E1412 were more high risk: IPI 2 (42% ROBUST/34% E1412), IPI ≥ 3 (58%/66%), and Ann Arbor stage III/IV disease (87%/97%). Importantly, there was a notable difference in the time from patient diagnosis to treatment: median 31 days for ROBUST and 21 days (22% 〉 31 d) for E1412. Only 6% of patients in ROBUST were treated within 2 weeks of diagnosis vs 30% in E1412. At a median follow-up of ~2.5 y for both studies, E1412 met its primary endpoint of improvement in PFS with 34% reduction in the risk of PD/death (2-y PFS: 76% vs 70%) for all patients, but did not reach statistical significance in ABC-DLBCL patients for 2-y PFS (71% vs 61%) or 2-y OS (88% vs 76%). ROBUST showed no significant improvement in the primary PFS endpoint (2-y PFS: 67% vs 64%) or 2-y OS (79% vs 80%) in ABC patients. Subgroup analyses of PFS comparing R2-CHOP vs R-CHOP control within each study suggested that certain baseline factors favor the R2-CHOP arm, including: female sex, high IPI score (≥ 3), non-bulky disease ( 〈 7 cm), and high Ann Arbor stage IV disease. Conclusion: While the ROBUST study design integrated state-of-the-art, real-time GEP to prospectively identify ABC-DLBCL patients with rapid lab turnaround time, cases of logistical delays in tissue submission for central analysis and staging procedures may have resulted in accrual of patients with lower-risk DLBCL and prolonged time from diagnosis to treatment. In contrast, E1412 retrospectively stratified patients by COO through GEP and was able to accrue higher-risk patients irrespective of COO within a shorter time from diagnosis to treatment, which among other differences (eg, smaller population size, study phase), could contribute to the improvement over R-CHOP control. Our comparative findings have significant implications for the design of future biomarker-driven trials and provide momentum for studies of novel combinations with R-CHOP in DLBCL. Further investigation into other factors, including dose intensity and their correlation with outcomes, will be presented. Disclosures Nowakowski: Celgene: Consultancy, Research Funding; NanoString: Research Funding; MorphoSys: Consultancy, Research Funding; Genentech, Inc.: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; Selvita: Membership on an entity's Board of Directors or advisory committees; Curis: Research Funding; Bayer: Consultancy, Research Funding. Chiappella:Servier: Other: advisory board, Speakers Bureau; Roche: Speakers Bureau; Teva: Speakers Bureau; Celgene: Other: advisory board, Speakers Bureau; Janssen: Other: advisory board, Speakers Bureau. Hong:Dana Farber Cancer Institute: Employment; Merck: Consultancy. Scott:Roche/Genentech: Research Funding; Celgene: Consultancy; Janssen: Consultancy, Research Funding; NanoString: Patents & Royalties: Named inventor on a patent licensed to NanoSting [Institution], Research Funding. Amengual:Appia Pharmaceuticals: Research Funding; Epizyme: Speakers Bureau. Leonard:BeiGene: Consultancy; Miltenyi: Consultancy; Sandoz: Consultancy; Gilead: Consultancy; Celgene: Consultancy; ADC Therapeutics: Consultancy; MorphoSys: Consultancy; ADC Therapeutics: Consultancy; Epizyme, Inc: Consultancy; Miltenyi: Consultancy; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy; Karyopharm Therapeutics: Consultancy; Akcea Therapeutics: Consultancy; Merck: Consultancy; Nordic Nanovector: Consultancy; Akcea Therapeutics: Consultancy; Bayer Corporation: Consultancy; Sandoz: Consultancy; MorphoSys: Consultancy; Gilead: Consultancy; BeiGene: Consultancy; AstraZeneca: Consultancy; Nordic Nanovector: Consultancy; Sutro Biopharma: Consultancy; Merck: Consultancy. Friedberg:Bayer: Honoraria, Other: Data & Safety Monitoring Committee; Acerta: Other: Data & Safety Monitoring Committee. Kostakoglu:F. Hoffman-La Roche: Consultancy; Genentech: Consultancy. Jurczak:Morphosys: Research Funding; Bayer: Research Funding; Roche: Research Funding; Incyte: Research Funding; Gilead: Research Funding; Celgene Corporation: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Research Funding; Servier: Research Funding; Takeda: Research Funding; TG Therapeutics: Research Funding; Celtrion: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding. Yamamoto:Bristol-Myers Squibb: Consultancy, Honoraria; Bayer: Research Funding; Celgene Corporation: Consultancy, Honoraria, Research Funding; Mundipharma: Consultancy, Honoraria, Research Funding; Astra-Zeneca: Consultancy, Research Funding; Eisai: Consultancy, Honoraria, Research Funding; Meiji Seika Pharma: Consultancy, Honoraria; ARIAD: Research Funding; MSD: Consultancy, Honoraria; Gilead Sciences: Research Funding; Ono: Consultancy, Honoraria, Research Funding; SymBio: Research Funding; HUYA/IQVIA Services Japan: Consultancy, Honoraria; AbbVie: Consultancy, Research Funding; Chugai: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria; Sumitomo Dainippon: Honoraria; Incyte: Research Funding; Janssen: Honoraria; Kyowa Kirin: Honoraria; Novartis: Honoraria, Research Funding; Otsuka: Honoraria; Sanofi: Honoraria; Solasia Pharma: Research Funding; Takeda: Consultancy, Honoraria, Research Funding. Czuczman:Celgene Corporation: Employment, Equity Ownership. Russo:Celgene Corporation: Employment, Equity Ownership. Hudak:Celgene Corporation: Employment, Equity Ownership; Novartis: Employment, Equity Ownership. Zhang:Celgene Corporation: Employment, Equity Ownership. Wade:Celgene: Employment, Equity Ownership. Kahl:ADC Therapeutics: Consultancy, Research Funding; BeiGene: Consultancy; TG Therapeutics: Consultancy; Seattle Genetics: Consultancy. Vitolo:Abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; F. Hoffmann-La Roche: Speakers Bureau; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. OffLabel Disclosure: Yes, these trials discuss off-label clinical trial investigation of lenalidomide plus R-CHOP in patients with newly diagnosed diffuse large B-cell lymphoma.