ALBERT

Description: Introduction: As previously reported, the combination of brentuximab vedotin with doxorubicin, vinblastine and dacarbazine (A+AVD) demonstrated a statistically significant improvement in modified progression free survival (modified PFS) compared with doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) in patients with newly diagnosed Stage III or IV classical HL in the phase 3 ECHELON-1 trial (NCT01712490). The benefit of A+AVD in the ITT population observed in the primary analysis was maintained at 3-years median follow-up [3-year PFS: A+AVD: 83.1% (79.9-85.9), ABVD: 76% (72.4-79.2)] and appears independent of interim PET status, disease stage, and prognostic risk factors. Here we present the efficacy and safety results of longer follow-up at a median 43.3 months. Methods: Newly diagnosed patients with Stage III or IV cHL were randomized 1:1 to receive A+AVD (n=664) or ABVD (n=670) intravenously on days 1 and 15 of each 28-day cycle for up to 6 cycles. The primary endpoint of the study was modified PFS per independent central review. The present follow-up PFS analysis is exploratory and per investigator assessment, with a cutoff date of June 17th, 2019. Patients with ongoing peripheral neuropathy (PN) at end of treatment were followed for resolution or improvement (defined as improved by ≥1 grade from worst grade as of the latest assessment) during the post-treatment follow-up period. Results: With a median follow-up of 43.3 months, the 42-month PFS per investigator for all patients was 82.4% (95% CI, 79.1-85.2) on the A+AVD arm and 76.2% (95% CI, 72.6-79.4) on the ABVD arm [overall HR 0.697 (95% CI, 0.547-0.890)]. Exploratory subgroup analyses of PET2(+) and PET2(-) patients showed a treatment effect in favor of A+AVD. The 42-month PFS in PET2(-) patients was 85.0% (95% CI, 81.6-87.7) for A+AVD and 79.6% (95% CI, 75.9-82.8) for ABVD [overall HR 0.695 (95% CI, 0.526-0.919)]; in PET2(+) patients 42-month PFS was 68.3% (95% CI, 54.5-78.7) for A+AVD and 51.5% (95% CI, 38.2-63.4) for ABVD [overall HR 0.552 (95% CI, 0.308-0.989)]. Upon continued follow-up, 81% (356/442) of patients with PN in the A+AVD arm had either complete resolution (64%, 283/442) or improvement (17%, 73/442) of their PN events compared with 83% (236/286) with either complete resolution (74%, 212/286) or improvement (8%, 24/286) in the ABVD arm. Among patients with ongoing PN after continued follow-up, the majority were Grade 1/2 events, with 89% (141/159; 59% Grade 1) and 95% (70/74; 65% Grade 1) on the A+AVD and ABVD arms, respectively. Overall survival data are not yet mature; per protocol, the final analysis will be performed after 112 deaths have occurred. Additional follow-up at an estimated median of ~4 years, including data from prespecified subgroups, will be presented. Conclusions: With a median follow-up of 43.3 months, A+AVD continues to provide a robust, durable benefit for patients with previously untreated Stage III or IV cHL compared with ABVD; the benefit is evident regardless of patient status at interim PET [PET2(+) or PET2(-)] and without the need for treatment intensification. PN continued to completely resolve or improve in patients on the A+AVD and ABVD arms. Together, these data further support the clinical advantages of A+AVD versus ABVD as treatment for patients with previously untreated Stage III or IV cHL. Disclosures Bartlett: Affimed Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Dynavax: Research Funding; Forty-Seven: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Immune Design: Research Funding; Janssen: Research Funding; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Medimmune: Research Funding; Merck: Research Funding; Millennium: Research Funding; Novartis: Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Straus:Elsevier (PracticeUpdate): Consultancy, Honoraria; Hope Funds for Cancer Research: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Honoraria. Dlugosz-Danecka:Servier: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Macrogenomics: Research Funding; Roche: Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau. Illes:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Feldman:Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau; Cell Medica: Research Funding; Amgen: Research Funding; Viracta: Research Funding; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; Pfizer: Research Funding; Portola Pharma: Research Funding; Roche: Research Funding; Eisai: Research Funding; Corvus: Research Funding; Roche: Research Funding; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Kyowa Hakko Kirin: Research Funding; Trillium: Research Funding. Smolewski:Roche: Other: Travel Expenses. Savage:Seattle Genetics, Inc.: Consultancy, Honoraria, Research Funding; BMS, Merck, Novartis, Verastem, Abbvie, Servier, and Seattle Genetics: Consultancy, Honoraria. Walewski:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding; Takeda: Honoraria, Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria; Gilead: Other: Travel Expenses; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Zinzani:Portola: 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; Immune Design: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sandoz: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Sanofi: Consultancy; Eusapharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau. Hutchings:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding; Genmab: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding; Novartis: Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Expenses, Research Funding. Radford:AstraZeneca: Equity Ownership, Research Funding; Novartis: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; GSK: Equity Ownership. Munoz:AstraZeneca: Speakers Bureau; Kite Pharma: Consultancy, Research Funding, Speakers Bureau; Pharmacyclics LLC an AbbVie Company: Consultancy, Research Funding, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; Fosunkite: Speakers Bureau; Kyowa: Consultancy, Honoraria, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding; Celgene: Research Funding; Portola: Research Funding; Incyte: Research Funding. Kim:Roche: Research Funding; Kyowa-Kirin: Research Funding; Novartis: Research Funding; J&J: Research Funding; Mundipharma: Research Funding; Celltrion: Research Funding; Donga: Research Funding. Advani:Cell Medica, Ltd: Consultancy; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Kura: Research Funding; Infinity Pharma: Research Funding; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Celmed: Consultancy, Membership on an entity's Board of Directors or advisory committees; Autolus: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agensys: Research Funding; Stanford University: Employment, Equity Ownership; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Research Funding; Kyowa Kirin Pharmaceutical Developments, Inc.: Consultancy; Regeneron: Research Funding; Millennium: Research Funding; Janssen: Research Funding; Roche/Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead Sciences, Inc./Kite Pharma, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Forty-Seven: Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees. Ansell:Mayo Clinic Rochester: Employment; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Trillium: Research Funding; Affimed: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; LAM Therapeutics: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Mayo Clinic Rochester: Employment; Mayo Clinic Rochester: Employment; Trillium: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Bristol-Myers Squibb: Research Funding; Seattle Genetics: Research Funding; LAM Therapeutics: Research Funding; Bristol-Myers Squibb: Research Funding; LAM Therapeutics: Research Funding; Regeneron: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Regeneron: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Trillium: Research Funding; Affimed: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; Bristol-Myers Squibb: Research Funding; Bristol-Myers Squibb: Research Funding; Mayo Clinic Rochester: Employment; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Seattle Genetics: Research Funding; Bristol-Myers Squibb: Research Funding; Trillium: Research Funding; Mayo Clinic Rochester: Employment. Younes:Roche: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Curis: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Abbvie: Honoraria; Takeda: Honoraria; Pharmacyclics: Research Funding; AstraZeneca: Research Funding; Genentech: Research Funding; Biopath: Consultancy; Xynomics: Consultancy; Epizyme: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; HCM: Consultancy; BMS: Research Funding; Syndax: Research Funding. Gallamini:Takeda: Consultancy; Roche: Consultancy. Miao:Millennium Pharmaceuticals, Inc., Cambridge, MA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment, Equity Ownership. Liu:Takeda: Employment. Fenton:Seattle Genetics, Inc.: Employment, Equity Ownership. Forero-Torres:Seattle Genetics: Employment, Equity Ownership, Honoraria, Research Funding.

Description: Background: Mantle cell lymphoma (MCL), an aggressive B-cell non-Hodgkin lymphoma, remains incurable with standard therapies. The highly selective, potent Bruton tyrosine kinase (BTK) inhibitor acalabrutinib was approved by the US Food and Drug Administration for the treatment of relapsed/refractory MCL based on clinical data showing a high rate of durable responses and a favorable safety profile (Lancet 2017;391:659-667). Here, we present long-term follow-up in these patients. Methods: Eligible patients were aged ≥18 years, had confirmed MCL, Eastern Cooperative Oncology Group performance status ≤2, and had relapsed and/or were refractory to 1-5 prior therapies. Exclusion criteria included prior BTK or BCL-2 inhibitor exposure and concomitant warfarin or equivalent vitamin K antagonists. Oral acalabrutinib 100 mg twice daily was administered until progressive disease or unacceptable toxicity. Response was assessed by investigators based on the Lugano classification (J Clin Oncol 2014;32:3059-3068).Analysis of minimal residual disease using next-generation sequencing (10-6) is ongoing for a subset of patients with available samples and will be presented upon completion. Results: A total of 124 patients were treated; 80% were men, and median age was 68 years (range, 42-90 years) with 65% aged ≥65 years. At baseline, 93% of patients had Eastern Cooperative Oncology Group performance status ≤1, 8% had bulky lymph nodes ≥10 cm, 72% had extranodal involvement, and 44%/17% had intermediate-/high-risk simplified MCL International Prognostic Index scores. The median number of prior therapies was 2 (range, 1-5); 24% were refractory to the most recent prior treatment. As of February 12, 2018, median time on study was 26.3 months (range, 0.3-35.1 months), and 40% of patients remain on treatment. Median relative dose intensity (ratio of actual to planned cumulative dose during drug exposure period) was 99% (range, 27%-100%). Investigator-assessed overall response rate was 81% (95% CI: 73%, 87%), with 43% (95% CI: 34%, 52%) achieving complete response (Table). Overall response rates were consistent across prespecified subgroups of tumor bulk, presence of refractory disease and number/type of prior treatment. Median duration of response was 25.7 months (95% CI: 17.5 months, not reached). Median progression-free survival (PFS) was 19.5 months (95% CI: 16.5 months, 27.7; Figure). Median overall survival (OS) was not reached; the estimated 24-month OS rate was 72% (95% CI: 64%, 80%). The most frequent adverse events (AEs; ≥20%) were primarily Grade 1/2 and included headache (38%), diarrhea (36%), fatigue (28%), cough (22%) and myalgia (21%). Grade 3/4 AEs (≥5%) included anemia (10%), neutropenia (10%) and pneumonia (6%). There were 13 patients (10%) with 16 cardiac events, including 4 Grade 3/4 events (3%) in 1 patient each (acute coronary syndrome, acute myocardial infarction, cardiorespiratory arrest, coronary artery disease). Four patients had hypertension events (3%); 1 event was Grade 3. The most common bleeding events were contusion (13%) and petechiae (9%); all bleeding events were Grade 1/2 except for 3 Grade 3 events (gastrointestinal hemorrhage, hematuria, hematoma). Grade 3/4 infections occurred in 15% of patients and none were Grade 5; there was one case of cytomegalovirus viremia and one case of pneumocystis jiroveci pneumonia (both Grade 2). Treatment discontinuation was primarily due to progressive disease (n=54; 44%) and AEs (n=10; 8%).Twelve AEs led to discontinuation in 10 patients; all of these AEs occurred in only 1 patient each.There were 43 deaths (35%), most commonly from progressive disease (n=29; 23%) or AEs (n=6; 5%). Deaths due to AEs included bilateral pulmonary embolism, critical aortic stenosis, myelodysplastic syndrome, pneumonia, suicide, and non-small cell lung cancer; none were considered to be related to acalabrutinib. Conclusion: Response to acalabrutinib remained consistent during long-term (〉24-month) follow-up, including high response rates, median PFS of 19.5 months, and a median OS that has not yet been reached, confirming efficacy in patients with relapsed/refractory MCL. The AE profile was largely similar to earlier reporting, with limited additional safety events observed with an additional year of follow-up. Disclosures Wang: Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Dava Oncology: Honoraria; AstraZeneca: Consultancy, Research Funding; Pharmacyclics: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Juno: Research Funding; MoreHealth: Consultancy; Acerta Pharma: Honoraria, Research Funding; Kite Pharma: Research Funding; Novartis: Research Funding. Rule:Celltrion: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences, Inc.: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Roche: Honoraria; Kite: Membership on an entity's Board of Directors or advisory committees. Zinzani:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Verastem: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Speakers Bureau; SERVIER: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celltrion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; TG Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; PFIZER: Honoraria, Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Honoraria, Speakers Bureau. Casasnovas:MSD: Honoraria; Merck: Honoraria; Takeda: Honoraria; Roche: Honoraria; Gilead Sciences: Research Funding; Roche: Research Funding; Janssen: Consultancy; Gilead Sciences: Consultancy; MSD: Consultancy; merck: Consultancy; takeda: Consultancy; Roche: Consultancy; Gilead Sciences: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Smith:Genentech: Research Funding; Portola: Research Funding; Pharmacyclics: Research Funding; Merck Sharpe Dohme and Corp: Consultancy, Research Funding; Seattle Genetics: Research Funding; Acerta Pharma BV: Research Funding. Morschhauser:BMS: Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Scientific Lectures; Epizyme: Consultancy; Roche: Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees. Panizo:Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees; Acerta Pharma: Research Funding; Roche: Consultancy, Speakers Bureau. Davies:Janssen: Consultancy, Honoraria; Karyopharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Research Funding; Acerta Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; F. Hoffman-La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy; ADC Therapeutics: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Research Funding. Jacobsen:Seattle Genetics: Consultancy; AstraZeneca: Consultancy; Merck: Consultancy. Kater:Janssen: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Acerta/AZ: Research Funding; Genentech: Honoraria, Research Funding. Robak:Gilead: Consultancy; Janssen: Consultancy, Honoraria; AbbVie, Inc: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria. Dua:Acerta Pharma: Employment. Frigault:AstraZeneca: Employment, Equity Ownership. Izumi:Acerta Pharma: Employment, Equity Ownership, Patents & Royalties: Acerta Pharma, various patents for ACP-196. Nguyen:Acerta Pharma: Employment. Patel:Acerta Pharma: Employment, Equity Ownership. Yin:Acerta Pharma: Employment. Jurczak:European Medicines Agency: Consultancy; Astra Zeneca/Acerta: Consultancy, Research Funding; Sandoz-Novartis: Consultancy; Janssen: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Afimed: Research Funding; Bayer: Research Funding; Beigene: Research Funding; Celgene: Research Funding; Epizyme: Research Funding; Nordic Nanovector: Research Funding; Merck: Research Funding; Morphosys: Research Funding; Pharmacyclics: Research Funding; Servier: Research Funding; Roche: Research Funding; TG Therapeutics: Research Funding.

Description: The first line treatment for primary mediastinal large B-cell lymphoma (PMLBCL) still remains a matter of debate even if the literature confirms that an anthracycline-containing regimen should be the main choice. The European experience shows the superiority of “third-generation” dose-dense regimen like MACOP-B (methotrexate, doxurubicin, cyclophosphamide, vincristine, bleomycin, prednisone) or VACOP-B (same as MACOP-B, with etoposide instead of methotrexate) over CHOP (cyclophosphamide, adriamycin, vincristine and prednisone) or CHOP-like regimen. The addition of rituximab to third-generation regimen does not seem to cause any advantages in terms of overall survival (OS) and progression free-survival (PFS), while external radiotherapy (RT) has shown a good efficacy as a consolidation strategy at the end of induction chemotherapy, especially in converting partial responses (PR) into complete responses (CR). Between October 1989 and April 2010, 98 (58 females and 40 males) previously untreated PMLBCL patients were diagnosed and subsequently treated at our Institution. All patients were treated with MACOP-B regimen, concurrent rituximab was administered in 57 patients (58.2%) and 67 patients (68.4%) received mediastinal RT. Among 57 patients who received rituximab, 37 (64.9%) underwent RT whereas, among 41 who did not receive rituximab, RT was delivered in 30 (group 4, 73.2%) patients. 11 patients (group 1, 11.2%) received chemotherapy alone and 37 (group 3, 37.8%) received besides immunotherapy and RT (Table 1). All patients were assessed at the diagnosis and after the treatment with computed tomography and positron emission tomography (after 2001) scan. Main aims of our study were the effectiveness of the regimen measured as overall response rate (ORR) and patients survival. Sixty-one (62.2%) out of 98 patients achieved a CR and 27 (27.6%) were in PR after 12 cycles of MACOP-B regimen (with or without rituximab). Twenty-one patients in PR after (immuno)chemotherapy converted the response into CR with mediastinal RT. At the end of the scheduled treatment, 82 patients (83.7%) achieved a CR and 6 a PR (6.1%), yielding an ORR of 89.8%. At a median follow-up of 5.6 years, 9 patients relapsed within the first 2 years of treatment. During the follow-up 15 patients died, of whom 13 as a consequence of disease relapse or progression. The projected OS at 17 years is 72% with a PFS and a disease free survival (DSF) of 86.8% and 88.4% respectively (Figure 1 A-C). The subgroup analysis shows a statistically significant difference in term of OS (p=0.0003) but not in term of PSF and DFS among the four groups of treatment (Figure 1 D-F). All the patients receiving consolidation RT obtained a CR without differences between subgroup 3 and 4. RT seems to have a small consolidative potential in patients who obtained CR after chemo-immunotherapy alone: there are no differences in term of DFS between subgroup 2 and 3. No statistically significant differences in terms of OS, PFS and DSF occurred among patients received rituximab or not, regardless of a subsequent RT. Our monocentric experience spans a period of 20 years and indicates that a third-generation regimen like MACOP-B is feasible and could be a standard of first line treatment for PMLBCL. In agreement with the literature, adding rituximab doesn’t improve the outcome. Mediastinal RT, delivered as a consolidative strategy, impacts on global survival and on CR rates. In particular, RT after third-generation regimen remains a good strategy to convert PR into CR, but it may be avoided in patients obtaining CR after (immuno)chemotherapy. Table 1 Group MACOP-B Rituximab Radiotherapy N (%) 1 Yes No No 11 (11.2%) 2 Yes Yes No 20 (20.4%) 3 Yes Yes Yes 37 (37.8%) 4 Yes No Yes 30 (30.6%) TOTAL N (%) 98 (100%) 57 (58.2%) 67 (68.4%) 98 (100%) Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Description: Background: A histologic finding of large cell transformation (LCT) in Mycosis fungoides (MF) is often associated with an aggressive clinical course and inferior prognosis (Arulogun et al. Blood 2008). In patients (pts) with advanced MF (stage IIB-IV), LCT has been established as an independent prognostic factor (Scarisbrick et al. JCO 2015). Although CD30 expression is observed more frequently in MF with LCT vs without LCT, a wide range of CD30 expression levels is observed in LCT lesions and the level of expression lacks prognostic value for MF (Vergier et al. Blood. 2000). The ALCANZA study (NCT01578499) demonstrated significantly better rates of objective response lasting ≥4 months (ORR4) (∆43.8%; p

Description: Introduction: MAVORIC was an open-label, multicenter, randomized phase 3 study evaluating the safety and efficacy of mogamulizumab (moga) compared to vorinostat (vori) in patients with mycosis fungoides (MF) or Sézary syndrome (SS) who had failed at least one prior course of systemic therapy (NCT01728805). Primary results have been reported (Kim et al. Lancet Oncol 2018) and were based on a data cutoff date of December 31, 2016. The primary endpoint was progression-free survival (PFS); patients in the moga treatment arm experienced significantly longer PFS compared to patients in the vori treatment arm (median 7.7 months vs 3.1 months; p

Description: The 26S proteasome plays a vital role in degrading regulatory proteins such as p53, p21, p27, NF-kB, I-kB, and bcl-2, that govern cell cycle, transcription factors activation, apoptosis and cell trafficking. Thus, the mechanisms by which bortezomib elicits its antitumor activity may vary among tumor types, and the extent to which each affected pathway is critical to the inhibition of tumor growth could also differ. The aim of this study was to determine the efficacy and toxicity of bortezomib in previously pretreated patients with peripheral T-cell lymphoma unspecified (PTCLU) and cutaneous T-cell lymphomas (CTCL). Each patient had to meet the following inclusion criteria to be enrolled in the study: histologically confirmed PTCLU or CTCL (according to REAL/WHO classification); any stage, any IPI, any bone marrow status; second or more relapse or refractory disease; age ≥ 18; ECOG performance status ≤ 2; Hb ≥ 10 g/dL, ANC ≥ 1.5x109/L and platelets ≥ 100 x 109/L; normal hepatic, renal and cardiac functions; and voluntary written informed consent. Bortezomib was given at 1.3 mg/m2 IV push on days 1, 4, 8 and 11 every 21 days. Restaging was done every 2 cycles. Patients were treated for up to a total of 6 cycles unless removed from study for failure to respond or toxicity. The response criteria were those recommended by NCI sponsored Working Group. A total of 30 patients will be enrolled; so far 10 patients entered and preliminary results of this trial will be presented.

Description: Background. Bortezomib, an inhibitor of the proteasome, is effective in relapsed mantle cell lymphoma (MCL) and indolent lymphomas and it is synergistic with Rituximab to enhance apoptosis and NFkB depletion. On these basis, the FIL conducted a phase II multicenter study aimed to evaluate safety and efficacy of Bortezomib in association with Rituximab in relapsed/refractory non-follicular Lymphoma (Linfocytic, LL and Marginal Zone Lymphoma, MZL) and MCL, not eligible to high dose chemotherapy with stem cell transplantation. Patients and methods. The study was a prospective single arm phase II trial, designed on Simon two-stage Optimal Design. Primary end-point was to obtain an Overall Response Rate (ORR) 〉 40%. The aim of this analysis is to evaluate long term follow-up of Bortezomib and Rituximab combination. A central histological revision was planned in all the patients at the enrollment. Inclusion criteria were: 18-75 years, relapsed/refractory LL, MZL, MCL after 1-4 lines. Treatment schedule was: one course of 1.6 mg/sqm Bortezomib weekly in combination with standard 375 mg/sqm Rituximab on days 1, 8, 15, 22 followed by two courses of four weekly intravenous bolus of Bortezomib alone; patients with complete (CR), partial remission and stable disease at the intermediate evaluation were planned to be given three further courses with the same schedule. Results. From September 2006 to March 2008, 55 patients were enrolled and six were excluded at central histological revision. Clinical characteristics were: median age 68 (50-74); 16 (33%) LL, 8 (16%) MZL, 25 (51%) MCL; 42 (86%) stage III/IV; 33 (67%) bone marrow involvement. Median number of previous treatments was 2 (range 1-7); 34 (69%) were Rituximab pretreated; 21 (43%) had refractory disease. Thirty (61%) patients completed the treatment and 233 courses were delivered (median: 4.7 courses/patient); 19 (39%) patients did not because of no response in 13, adverse events in five, with only one toxic death due to interstitial pneumonia. ORR was 53% (CR 26.5%); no response was seen in 43% and 4% were not evaluable for response. ORRs by clinical subgroup were: LL 37%, MZL 50%, MCL 64%; Rituximab pretreated 62%, Rituximab naïve 33%; relapsed 64% and refractory 38%. With a median follow-up of 85 months, median Overall Survival (OS) was 61.5 months (95%CI: 35.0-81.5), with 5-years OS 51% (95% CI: 36-65) and median Progression Free Survival (PFS) was 8.9 months (95%CI: 5.3-18.3), with 5-years PFS 16% (95% CI: 7-28%). Five-years PFS by histology was: 12% (95% CI: 2-31) for LL, 17% (95% CI: 5-34) for MCL and 19% (95% CI: 11-53) for MZL. PFS rates were not different between Rituximab pretreated versus naïve nor international prognostic index 1-2 versus 3-4-5 nor refractory versus relapsed. By number of previous therapies, 5-years PFS for 1 previous therapy versus 2 versus 3 or more was: 24%, 14% and 13%, respectively, p=0.36. Conclusions. Weekly infusion of Bortezomib in combination with Rituximab is effective in relapsed/refractory indolent and MCL and represents a treatment option in this setting of patients. Disclosures No relevant conflicts of interest to declare.

Description: Background: PI3Kδ signaling is at the crossroads of B-cell receptor signaling pathways that are major drivers of survival and proliferation of B-cell malignancies, making it an attractive target for drug development. PI3Kδ inhibitors have proven clinical efficacy in relapsed or refractory non-Hodgkin's lymphoma (NHL); however, the high incidence of immune-related adverse events (irAEs) of early generation PI3Kδ inhibitors has limited their use. Management of toxicities by daily dose reduction may reduce the incidence of toxicities but also can lead to potential loss of efficacy, therefore novel approaches are needed to maximize clinical utility. ME-401 is an oral once-daily selective PI3Kδ with a molecular structure and pharmacodynamic characteristics that are distinct from other PI3Kδ inhibitors, either approved or under development. ME-401's high volume of distribution, long half-life (~30 hours), and intracellular penetration/ retention kinetics predict a significantly higher tumor exposure to drug relative to plasma which has been borne out in pre-clinical mouse lymphoma studies. These properties allow use of an intermittent dosing schedule to minimize immune-related toxicities common to other PI3kδ agents. ME-401 has demonstrated high and objective response rates (ORR) in both FL and CLL/SLL; 80% in 50 patients with relapsed/refractory (R/R) FL and 100% in 14 patients with R/R CLL/SLL (Zelenetz et al 2019). During the Phase 1b dose escalation study of ME-401 administered on a continuous daily dosing schedule (CS, 28-day cycle), no dose limiting toxicities were identified, and the first dose level of 60 mg was selected for further development due to its high response rate. Delayed (≥ cycle 3) grade 3 AEs such as diarrhea and rash occurred in approximately one third of patients (Zelenetz, 2018). These AEs are likely related to on-target effects on T-regulatory cells (T-regs) resulting in immune-mediated toxicity. With the goal of improving tolerability we developed a novel dosing approach for ME-401, reducing dose intensity via intermittent dosing (IS) 7 days on/21 days off, with the goal of allowing Treg repopulation. The IS is introduced after an initial period (2 cycles) of daily dosing for tumor debulking. Preliminary evaluation of this novel schedule resulted in a marked decrease in delayed Grade 3 irAEs compared to the CS. The ME-401-003 (TIDAL) study was designed to further evaluate risk-benefit profiles of these two treatment schedules of this potent PI3Kδ inhibitor in patients with relapsed or refractory FL. Study Design and Methods:ME-401-003 (TIDAL) is a global study of ME-401 in patients with FL after failure of ≥2 prior systemic therapies and will enroll approximately 166 subjects. Subjects must have received prior therapy with an anti-CD20 antibody and chemotherapy with an alkylating agent or purine analogue with adequate organ and bone marrow function; no prior therapy with a PI3Kδ is allowed. Upon meeting eligibility criteria, patients are randomized to the CS or IS dosing group with a 1:1 allocation ratio at baseline and receive open-label ME-401 at 60 mg daily for the first two cycles. The stratification factors for randomization are disease status (relapsed or refractory) and tumor bulk. Patients with stable disease or an objective response after 2 cycles will then continue onto the blinded, placebo-controlled portion of the study and will receive ME-401 either on a CS or an IS. Patients who experience disease progression on IS will be able to receive open-label ME-401 on CS to explore the recapture of response. Subjects who develop grade ≥ 2 adverse of special interest (AESI) will have study drug halted and upon resolution of AE will continue on open label IS to mitigate toxicity. The primary objectives are ORR using Lugano Response Criteria, as determined by an Independent Response Review Committee, and tolerability defined as the rate of AEs requiring dose modification or study drug discontinuation utilizing a sample size of 75 subjects per treatment schedule. A correlative study will evaluate the effects of ME-401 on T-cell subsets, cytokines and chemokines. The study opened to enrollment in December 2018 with sites planned in North America, Europe, Asia, New Zealand and Australia. (NCT03768505) Disclosures Zelenetz: Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astra-Zeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; DAVA Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics/AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; DAVA Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Verastem: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech/Roche: Consultancy, Membership on an entity's Board of Directors or advisory committees; MEI Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Zinzani:VERASTEM: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELLTRION: 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-CILAG: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SERVIER: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANDOZ: Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; IMMUNE DESIGN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; CELGENE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; PORTOLA: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; ROCHE: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; EUSAPHARMA: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; KYOWA KIRIN: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SANOFI: Consultancy. Buske:Janssen: Honoraria, Research Funding, Speakers Bureau; Amgen: Research Funding; Roche: Honoraria, Research Funding, Speakers Bureau; Pfizer: Honoraria; Bayer: Research Funding; Celltrion: Honoraria, Speakers Bureau; Hexal: Honoraria, Speakers Bureau. Ribrag:AZ: Membership on an entity's Board of Directors or advisory committees; argenX: Research Funding; Infinity: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Epizyme: Honoraria, Research Funding; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees. Cunningham:Bayer: Research Funding; Amgen: Research Funding; MedImmune: Research Funding; Clovis: Research Funding; Merck: Research Funding; 4SC: Research Funding; Eli Lilly: Research Funding; Merrimack: Research Funding; AstraZeneca: Research Funding; Celgene: Research Funding; Sanofi: Research Funding; Janssen: Research Funding. Jurczak:Gilead: Research Funding; Takeda: Research Funding; Celtrion: Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Servier: Research Funding; Incyte: Research Funding; Celgene Corporation: Research Funding; TG Therapeutics: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Research Funding; Loxo: Membership on an entity's Board of Directors or advisory committees, Research Funding; Morphosys: Research Funding; Novo Nordisk: Research Funding; Roche: Research Funding; Sandoz: Membership on an entity's Board of Directors or advisory committees, Research Funding. Abrisqueta:Celgene: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Janssen: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel, Accommodations, expenses, Speakers Bureau. Brown:Kite, a Gilead Company: Consultancy, Research Funding; Pharmacyclics: Consultancy; Pfizer: Consultancy; Juno/Celgene: Consultancy; BeiGene: Consultancy; Loxo: Consultancy, Research Funding; Genentech/Roche: Consultancy; Gilead: Consultancy, Research Funding; Catapult Therapeutics: Consultancy; Dynamo Therapeutics: Consultancy; AstraZeneca: Consultancy; Novartis: Consultancy; Octapharma: Consultancy; Invectys: Other: Data safety monitoring board; Morphosys: Other: Data safety monitoring board; Teva: Honoraria; Janssen: Honoraria; Sun Pharmaceuticals: Research Funding; Verastem: Consultancy, Research Funding; TG Therapeutics: Consultancy; Sunesis: Consultancy; Acerta Pharma: Consultancy; AbbVie: Consultancy.

Description: Introduction: The B-lymphocyte, lineage specific surface antigen CD19 is broadly and homogeneously expressed in most B-cell non-Hodgkin's lymphomas (NHL). As a co-stimulatory molecule of the B-cell receptor complex it is an important regulator of transmembrane signals in B-cells. Phosphorylation of intracellular tyrosine residues of CD19 may augment signal transduction in multiple pro-survival and proliferation pathways ( e.g. PI3K and BTK). This makes CD19 an attractive target for the treatment of B-cell malignancies. MOR208 is a Fc-enhanced CD19 monoclonal antibody. The Fc-enhancement of MOR208 leads to a potentiation of antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP). MOR208 also induces direct cytotoxicity, potentially by disrupting B-cell receptor (BCR) signalling. Thus MOR208 may have clinical use as a new therapeutic agent in patients with (R-R) B-cell malignancies. Methods: This is an open-label, multicenter, phase IIa study of MOR208 in R-R NHL patients progressing after at least one prior rituximab-containing therapy. Patients were enrolled into 1 of 4 cohorts of aggressive and indolent (i) NHLs. Treatment comprised single-agent MOR208, 12 mg/kg IV, weekly, for 8 weeks (2 cycles), which could continue for 4 additional weeks in patients with at least stable disease (SD) after 2 cycles. Patients with complete responses (CRs) or partial responses (PRs) at 12 weeks could continue with bi-weekly or monthly MOR208 treatment until progression. The primary endpoint was the objective response rate (ORR), which was assessed by the investigator. Secondary endpoints included progression-free survival (PFS), duration of response (DoR) as well as incidence and severity of adverse events (AEs). This analysis includes the evaluation of potentially predictive and prognostic biomarkers in DLBCL and iNHL cohorts. Results: In total, 92 patients were enrolled including 35 (38%) with DLBCL and 45 (49%) with iNHL. Median age was 71 years in the DLBCL cohort and 66 years in the iNHL cohort. 30 (86%) DLBCL patients and 40 (89%) iNHL patients had stage III-IV disease; 12 (34%) and 21 (47%) had received ≥3 prior lines of therapy, respectively. In the DLBCL cohort 24 (69%) patients were rituximab refractory as were 22 (49%) patients in the iNHL cohort. ORR was 26%, including 2 CRs and 7 PRs in the DLBCL cohort, and 29% including 5 CRs and 8 PRs in the iNHL cohort; 5/9 and 5/13 responders were rituximab refractory, respectively. The disease control rate (DCR, CR+PR+SD) was 40% in the DLBCL and 73% in the iNHL cohorts. Reduction in target lesion size was also seen in 5/6 DLBCL and 12/16 iNHL patients with SD (central assessment). Median DoR was 20 months for DLBCL patients (95% CI 11.3-not available; 3 ongoing) and not reached for iNHL (6 ongoing), with the longest duration of response lasting 〉26 months in both cohorts. In patients with rituximab non-refractory and refractory tumors the 12-month PFS rate was 40% in both the DLBCL and iNHL cohorts. DCR (65% vs 54%; p=0.35) and PFS (median 6.6 vs 5.3 months, hazard ratio [HR] 0.85, 95% CI 0.45-1.6; p=0.59) were comparable. PFS was significantly longer in patients with a baseline natural killer (NK) cell count 〉100 cells/μl vs ≤100 cells/μl, (HR 0.16, 95% CI 0.06-0.42, p=0.0003). Infusion-related reactions (IRRs) were seen in 4/35 (11%) and 5/45 (11%) patients in the DLBCL and iNHL cohorts, mostly of grade 1-2 and duringthe first infusion of cycle 1. The incidence of grade ≥3 neutropenia, anemia and thrombocytopenia was 17%, 9% and 6% in DLBCL and 4%, 0% and 2% in iNHL patients, respectively. The incidence of MOR208 treatment-related serious adverse events was 6% in DLBCL and 4% in iNHL patients. No treatment-related deaths were reported. Conclusions: MOR208 12 mg/kg showed encouraging preliminary single-agent activity in patients with R-R DLBCL or R-R iNHL, with long lasting responses, and was equally efficacious in NHL patients with rituximab refractory and non-refractory disease. Target lesion shrinkage was demonstrated in the majority of patients with SD. Patients with a high peripheral NK cell count at baseline benefited more from MOR208 treatment. MOR208 was generally well tolerated, with a favorable safety profile including patients on long-term treatment. The promising results of this trial further justify the development of MOR208 as part of a combination therapy in B-cell malignancies. Disclosures Jurczak: Pfizer: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gillead: Research Funding; Janssen: Research Funding; Celtrion: Research Funding; Bayer: Research Funding; Sandoz-Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Roche: Speakers Bureau; Teva: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; Acerta: Research Funding; MorphoSys: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Zinzani:Celgene: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Gaidano:Roche: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; MorphoSys: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau. Goy:Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Writing support, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Genentech: Research Funding. Robak:MorphoSys AG: Research Funding. Buske:Celltrion, Inc.: Consultancy, Honoraria. Ambarkhane:MorphoSys: Employment. Winderlich:MorphoSys AG: Employment, Patents & Royalties. Dirnberger-Hertweck:MorphoSys AG: Employment. Endell:MorphoSys AG: Employment, Patents & Royalties. Blum:MorphoSys: Research Funding.