ALBERT

Description: Background: The cure rate for advanced classical Hodgkin lymphoma (cHL) is approximately 70%, which is calculated based on data from clinical trials performed in North American and/or European countries (Canellos GP, et al. N Engl J Med. 1992;327:1478-84; Carde P, et al. J Clin Oncol. 2016;34:2028-36; Gordon LI, et al. J Clin Oncol. 2013;31:684-91). However, there are limited outcome data available in other countries, apart from some small hospital-based studies (Ramirez P, et al. Rev Bras Hematol E Hemoter. 2015;37:184-9; Law MF, et al. Arch Med Sci. 2014;10:498-504; Jaime-Pérez JC, et al. Oncologist. 2015;20:386-92; Omer Al-Sayes FM, Sawan A. J Taibah Univ Med Sci. 2006;1:48-56). The B-HOLISTIC retrospective chart review study seeks to address the paucity of data on cHL treatment patterns, clinical outcomes, and healthcare resource utilization in 13 countries across Latin America, Africa, Middle East, and the Asia-Pacific region. Methods: The study will collect data from approximately 2,600 patients aged ≥18 years and newly diagnosed with stage IIB-IV cHL or relapsed/refractory cHL (RRHL) between 01 January 2010 and 31 December 2013, and will follow them until death or chart review, whichever occurs first. The primary objective is to describe progression-free survival (PFS) in patients with RRHL. Secondary objectives include describing demographic and clinical characteristics, clinical outcomes (overall survival, best clinical response after completion of treatment, response duration), key adverse events associated with each line of therapy, and cHL-related healthcare resource use. Results: As of 14 May 2018, a total of 165 patients from 12 sites have been included in the interim analysis, predominantly from Turkey and South Korea. At this time, 150 patients had cHL and 24 patients had RRHL, including 9 patients who were enrolled in the cHL group and had a documented relapse/progression during the study period. Here, we report the results of the newly diagnosed cHL group; data from the RRHL group will be reported in subsequent publications. At diagnosis, 64.7% of the cHL group were male, with a median age of 36.5 years (range, 18-89 years); 22.7% had stage IV disease, 30% had extranodal disease, 59.3% had 'B' symptoms, and 34.9% had an International Prognostic Score (IPS) of ≥4. Patients were classified as 13.3% in stage I-IIA; 24% in stage IIB; 53.3% in stage IIIA-IVB; and 9.3% as unknown. Patients classified as stage I-IIA are a deviation from the clinical study protocol and will be removed from the final study analysis. The proportion of patients alive was 94%, with the cause of death reported as either HL-related (44.4%), due to an adverse event (11.1%), or other (44.4%). Positron emission tomography (PET) or PET-computed tomography (CT) imaging was performed in 58.5% of patients at baseline, 48% of patients at interim, and 36.6% at end-of-treatment; CT imaging was performed in 68.7% of patients at baseline, 83.6% of patients at interim, and 59.7% of patients at end-of-treatment. At frontline treatment, 95.3% of patients received chemotherapy (mostly doxorubicin, bleomycin, vinblastine, dacarbazine [ABVD], 92.3% [median number of cycles, 6; range, 2-8]), 22.7% of patients received radiotherapy, with 22% of patients receiving radiotherapy and chemotherapy (median total dose, 34.5 Gy; range, 24-45 Gy). The majority of patients received involved-field radiotherapy (53.1%), with other modalities including involved-node (21.9%), involved-site (18.8%), whole body (3.1%), or other (3.1%). The proportion of patients who achieved a complete or partial response to frontline treatment was 52.1% and 21.1%, respectively. The PFS for treatment in frontline cHL in the overall patient population at 48 months was 81% (95% CI, 73.1-86.7; Figure 1), with a median duration of follow-up of 58.9 months (range, 2.6-128.3 months). The PFS for treatment in frontline cHL excluding ineligible patients classified as stage I-IIA (13.3%) at 48 months was 78.9% (95% CI 69.7-85.6). Due to the retrospective nature of this study, adverse events were under-reported and will be presented once the data are mature. Conclusion: The B-HOLISTIC study is ongoing, with final patient enrolment anticipated in December 2018. These interim data provide real-world information on the incidence, treatment, and outcomes of cHL in countries where little is known about this patient population. Disclosures Ferhanoglu: Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees. Yeh:GNT Biotech & Medicals Crop.: Research Funding. Brittain:Takeda: Membership on an entity's Board of Directors or advisory committees. Karduss:Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Kwong:Bayer: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria; Astellas: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Song:Peking University Cancer Hospital (Beijing Cancer Hospital): Employment. Zerga:Bristol Myers Squibb: Other: Conference fees; Roche: Other: Conference fees; Janssen: Other: Conference fees; Takeda: Other: Conference fees. Blair:Takeda Pharmaceuticals International Co.: Employment. Dalal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA: Employment, Equity Ownership. Wan:Takeda Pharmaceuticals International Co.: Employment. Hertzberg:Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees.

Description: Abstract 674 Background: Paradigm changes in cancer therapy have shifted care to primarily outpatient-based regimens. Venous thromboembolism (VTE) is a well-known complication of cancer but contemporary data regarding the burden of VTE in the outpatient versus inpatient cancer settings are lacking. Methods: We conducted a retrospective, observational, cohort study to examine the incidence of VTE in inpatients and outpatients with cancer utilizing a linked database formed from the US Premier Perspective™ and the I3 Pharma Informatics healthcare claims databases, which provide data from the inpatient and outpatient settings, respectively. Patients with ≥1 inpatient or outpatient claims containing a diagnosis of cancer in any position (ICD-9-CM codes: 140.XX-208.99) from January 2005 to June 2009 were identified. VTE including deep vein thrombosis (DVT: ICD-9-CM codes 451 and 453) or pulmonary embolism (PE: ICD-9-CM codes 415.1–415.19) occurring in the inpatient or outpatient setting were identified over the 12 months post-index period. Data regarding demographics, clinical characteristics and cost were assessed. Multivariate analyses were conducted to adjust for differences in patient characteristics before and after the index event. Results: A total of 17,874 patients with cancer were identified. Over the 12 months post-index period, 996 (5.6%) of these patients had VTE (mean age 59.6 years; 46.7% male) and 16878 (94.4%) patients did not (mean age 58.3 years; 46.3% male). Patients with VTE had a higher mean Charlson Comorbidity Index (CCI) score at baseline than the non-VTE patients (0.9 vs. 0.7; P

Description: Background and Aim: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL) wherein those with advanced stage have a poor prognosis. The objective of this study was to describe clinical characteristics and survival in MF patients who were refractory or had relapsed after a first systemic therapy. Methods: A retrospective chart review study was conducted at 27 sites in Europe. Patients enrolled had a diagnosis of MF and proved to be relapsed/refractory (R/R) prior to 1-Jan-2016 after a first systemic therapy. Overall survival (OS) and progression-free survival (PFS) were estimated from the date of R/R event (defined as the index date) using Kaplan-Meier estimates. PFS was defined as death, progression, second relapse or refractory, or presence of subsequent treatment after index date. Results: This study included 104 advanced R/R MF patients with a median age of 54.5 years (range: 21-82). The median follow-up was 3.5 years (range: 0-20.7) after index date. In total 80% of patients experienced a second R/R, with a median time to second R/R of 15.8 months (range: 0.6-174.6). The median age at death was 65 years (range: 42-85). In total 39 deaths (37.5%) were observed. Among those patients who had a known cause of death (N=35), 18 died of CTCL progression, 11 of CTCL complication or drug toxicity and 7 of other causes. The estimated median OS was 11.5 years (95% CI: 6.5 - not reached). The median PFS was 1.3 years (95% CI: 1.0-2.1). Conclusions: The high rate of R/R and low PFS suggest that the clinical burden of R/R MF is significant in five European countries, and recently approved targeted therapies have the potential of improving outcomes. Disclosures Bagot: Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Illidge:Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics, Inc.: Research Funding; Div of Cancer Sciences, Faculty of Biology, Medicine and Health, Univ of Manchester, National Institutes of Health and Research Biomedical Research Center, Manchester Academic Health Sciences, Christie Hospital National Health Service Foundation Trust: Employment. Dalal:Takeda: Employment. Zomas:Takeda: Employment. Trinchese:Takeda: Employment. Little:Takeda: Employment. Bent-Ennakhil:Takeda Pharmaceuticals International AG: Employment. Ortiz-Romero:Actelion: Consultancy, Membership on an entity's Board of Directors or advisory committees; 4SC: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; miRagen: Membership on an entity's Board of Directors or advisory committees; PLCG1: Patents & Royalties; Kyowa: Membership on an entity's Board of Directors or advisory committees; Innate Pharma: Membership on an entity's Board of Directors or advisory committees; MEDA: Research Funding.

Description: OBJECTIVES: Several agents have recently been approved for relapsed/refractory multiple myeloma (RRMM), providing patients and providers with more treatment options. The existing literature on patient preferences for MM treatments is limited. This study aims to quantify these preferences using a discrete-choice experiment (DCE) survey coupled with a best-worst scaling (BWS) exercise to elicit treatment priorities and unmet needs. METHODS: The survey design utilized both a DCE and a BWS exercise that included attributes and levels that overlapped between the two types of patient preference questions (DCE and BWS) to provide multiple sources of information on treatment preferences. The attributes for the DCE and BWS exercise were informed by patient focus groups. The final DCE included six attributes with varying levels: progression-free survival (PFS, 6-24 months); risk of heart failure (0%-5%); peripheral neuropathy (none, mild-to-moderate, severe); risk of low blood counts, combining thrombocytopenia and neutropenia (0%-70%); gastrointestinal (GI) problems (none, nausea and vomiting, diarrhea, constipation); and mode and frequency of administration (daily and weekly pill, weekly injection, intravenous [IV] infusion 4 hours per week, IV 1 hour twice a week). The BWS exercise included 18 items (the modes and frequency of administration included in the DCE, additional treatment convenience items, mild and serious adverse events, and treatment side-effects). The final survey was administered online to patients recruited from the Multiple Myeloma Research Foundation CoMMpass study (NCT01454297). For the DCE data, latent-class analysis was used to identify patient subgroups with systematically different preferences. The relative strength of preference for each attribute level (i.e., relative preference weights) was estimated for all subgroups and was used to calculate the relative importance of attributes. For each item in the BWS exercise, a relative score was calculated by subtracting the number of times a feature was chosen as least bothersome from the number of times it was chosen as most bothersome, then dividing by the total number of times appeared in the design. RESULTS: The final sample consisted of 94 patient respondents with RRMM. Patients had an average age of 65 years, and 59% were male. The latent-class analysis identified two subgroups of respondents with systematically different preferences (Figure 1). Both subgroups expressed a willingness to trade PFS for less treatment toxicity. Members of subgroup 1 placed the greatest relative importance on toxicities (nerve damage, risk of low blood counts, GI problems). A change in nerve damage from none to severe was the most important attribute to subgroup 1, approximately 1.8 times more important than the relative importance of a change in the risk of low blood counts from 0% to 70%, and 2.7 times more than the relative importance of a change in PFS from 6 months to 1 year. Members of the second subgroup considered PFS the most important attribute, followed by nerve damage and mode of administration. Subgroup 2 considered the relative importance of a change in PFS from 6 months to 2 years to be more than two times as important as the relative importance of changes in all other attributes. In the BWS exercise, respondents evaluated kidney complications and low white blood cell count as the most bothersome medicine characteristics, while taking pills once a week for 3 weeks per month or pill taken daily were the least bothersome (most favorable) characteristics. CONCLUSIONS: Patients with RRMM place importance on PFS and nerve toxicity when considering treatment features and modes of administration. Results from the preference study indicate that there are subgroups of patients with systematically different treatment preferences. Understanding how different patients value treatment attributes may help decision makers improve the quality of patient-centered care. Figure 1. Figure 1. Disclosures Mansfield: Takeda Pharmaceuticals International Co: Consultancy; Genentech: Consultancy. Chari:Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Array Biopharma: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy; Pharmacyclics: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; The Binding Site: Consultancy. Cole:Cancer Support Community myeloma advisory board: Membership on an entity's Board of Directors or advisory committees; University of Michigan: Employment. Kaufman:Karyopharm: Other: data monitoring committee; Roche: Consultancy; BMS: Consultancy; Janssen: Consultancy; Abbvie: Consultancy. Siegel:BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau; Karyopharm: Consultancy, Honoraria; Merck: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Zonder:Takeda: Honoraria; Alnylam: Honoraria; Celgene: Consultancy, Honoraria; Janssen: Honoraria; Coelum: Honoraria; BMS: Research Funding; Pharmacyclics: Other: DSMC. Mange:Takeda Pharmaceutical Company: Consultancy. Dalal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA: Employment, Equity Ownership. Mikhael:Onyx, Celgene, Sanofi, AbbVie: Research Funding.

Description: INTRODUCTION: Chronic myeloid leukemia (CML) is a bone marrow and blood disorder accounting for 15% of adult leukemia. A shift in CML management has occurred over the past decade with the introduction of tyrosine kinase inhibitors (TKIs), changing CML status from fatal to a chronic, lifelong illness. However, an association between TKI use and cardiovascular events has been observed. This study aimed to compare major adverse cardiac events (MACE), arterial occlusive events (AOEs), and venous thrombotic events (VTEs) among CML patients in chronic phase (CP-CML) treated with different TKIs. METHODS: A retrospective observational study of adult (aged ≥18 years) CP-CML patients prescribed a TKI was conducted using the IBM® MarketScan® Research Databases from July 2012-June 2017. The index date was defined as the index drug prescription date, identified based on TKI use during the identification period (January 2013-December 2016) in hierarchical order: ponatinib, bosutinib without ponatinib, and other TKIs (imatinib, dasatinib, nilotinib) excluding ponatinib and bosutinib. Patients were required to have continuous health plan enrollment for ≥6 months pre-index date (baseline period) and at least 6 months post-index date (follow-up period). Patients with use of one or two previous TKI(s) before the index date were examined separately. Cardiovascular events occurring through the earliest of discontinuation of index TKI, switch to another TKI, or end of follow-up period using ICD-9/10-CM diagnosis codes were calculated as the number of events per 100 person-years. MACE was defined as a composite of stroke (hemorrhagic stroke and ischemic stroke), myocardial infarction, and inpatient death; AOEs included cardiovascular, cerebrovascular, and peripheral vascular events; VTEs included pulmonary embolism and deep vein thrombosis. RESULTS: After applying the selection criteria, 161 patients had one previous use of a TKI, with 50 ponatinib, 80 bosutinib and 31 other TKI patients. Mean ages were 54, 57, and 58 years for ponatinib, bosutinib, and other TKI cohorts, respectively. Most ponatinib patients initiated treatment with a dose of 45 mg (60%); most bosutinib patients initiated with a dose of 500 mg (53%) . For patients with use of one previous TKI, the average Charlson Comorbidity Index score was 1.4 for ponatinib, 1.8 for bosutinib and 0.8 for other TKI patients. Common baseline comorbid conditions by drug included anemia (ponatinib: 50%; bosutinib 31%; other TKI: 19%), hypertension (ponatinib: 32%, bosutinib: 43%, other TKI: 29%), and diabetes (ponatinib: 16%; bosutinib: 28%; other TKI: 10%). CP-CML patients were observed to have cardiovascular events prior to index TKI use, especially MACE (ponatinib: 4%, bosutinib: 16%, other TKI: 3%), and AOEs (ponatinib: 12%; bosutinib: 25%; other TKI: 19%). During the follow-up period, no significant differences were found for cardiovascular events across patients with TKI use (Table 1); the incidence of MACE was 4.7-8.3, AOEs: 25.8-33.3, and VTE: 2.3-9.1 (in 100 person-years). For those with use of two types of TKIs before the index date, 29 ponatinib, 29 bosutinib, and 4 other TKI patients were identified, with an average age of 51, 59, and 65 years, respectively. A similar trend was observed for patients with use of two prior TKIs. CONCLUSION: CP-CML patients treated with different TKIs (ponatinib, bosutinib, imatinib, dasatinib, and nilotinib) did not have different incidence of cardiovascular events (MACE, AOEs, VTEs) in this small cohort of real-world patients with ≥6-month of follow-up. The results were consistent among patients with prior use of one and two TKI types. Disclosures Levy: Takeda (Millennium Pharmaceuticals, Inc.): Consultancy. Xie:STATinMED Research: Employment. Wang:STATinMED Research: Employment. Neumann:Takeda (Millennium Pharmaceuticals, Inc.): Employment. Srivastava:Takeda (Millennium Pharmaceuticals, Inc.): Employment. Naranjo:Takeda (Millennium Pharmaceuticals, Inc.): Employment. Zhang:STATinMED Research: Employment. Dalal:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd, Cambridge, MA, USA: Employment, Equity Ownership.

Description: INTRODUCTION Peripheral T cell lymphomas (PTCL) are a rare and heterogenous group of aggressive non-Hodgkin lymphomas (NHL) that develop from mature T- and natural killer cells. They comprise approximately 10% of all newly diagnosed cases of NHL in Western populations. The current study characterizes real-world treatment patterns and outcomes among patients with PTCL in France and the United Kingdom (UK) in the first-line (1L) setting. METHODS A retrospective medical chart review study was undertaken at geographically disparate clinical sites in France and UK, where treating physicians were responsible for patient selection and data collection via structured case report forms. Adults (≥18 years) with newly diagnosed with PTCL between January 1, 2014 and December 31, 2016 were randomly selected for inclusion in the study. Eligible patients had received at least 1L treatment (1LT) for PTCL and had available clinical data for ≥1 year after PTCL diagnosis or until death. Patients enrolled in a clinical trial for 1L PTCL at any time between diagnosis and end of follow-up or who had any prior unresolved malignancy within 5 years of PTCL diagnosis were excluded. Demographic, clinical, and immunophenotypic/cytogenetic profiles of PTCL patients were assessed at diagnosis. Treatments received and best response as reported by the treating clinician (categorized as complete response [CR], partial response [PR], stable disease [SD], and progressive disease [PD]) at the end of 1LT are described. Data from both countries were pooled for the current analysis. RESULTS Overall, 32 haematologist/oncologists (France, 15; UK, 17) with a median of 12.5 years of clinical practice participated in the study. Most physicians in France practiced at a university hospital or a regional hospital centre (73.3%). In the UK, most physicians practiced at a specialist cancer/ tertiary referral treatment centre (47.1%). A total of 109 patients (France, 53; UK, 56) received at least 1L PTCL treatment during the study period. The median age at diagnosis was 63 years (range, 19 to 84 years), with a male predominance (57.8%). Eighty percent of patients had an ECOG performance status of 0-1 at diagnosis. B symptoms were present in 59.6% and extranodal disease was present in 35.8% patients at diagnosis. Most patients (72.5%) had stage III or IV disease and (64 of 102) 62.75% were classified as intermediate risk (score of 2-3) as per the International Prognostic Index. The most common histological subtypes were PTCL-not otherwise specified (NOS) (37.6%), angioimmunoblastic T-cell lymphoma (29.4%), and systemic anaplastic large cell lymphoma (20.2%). The median duration of follow-up was 34 months from the start of 1L PTCL treatment. Of those tested, 60.4% patients were positive for CD30 (information on threshold was not reported). Only 19.3% patients underwent testing for any cytogenetic marker. During follow-up, 28.4% of patients had died. In the 1L setting, 59.6% and 26.6% patients were treated with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) and with CHOEP/CHOEP‐like regimens (Table). Median duration of 1LT was 4.9 months. Stem cell transplant was undertaken in 29.4% patients as part of 1L treatment, of which 84.4% were autologous. PET-CT was used for response assessment in 56% of patients. Best response within 1 year of completing 1LT and before start of 2L treatment was assessed in 75/109 [68.8%] patients (Table); of whom 80% (60 patients) were reported to have a complete response (Table), and about 39% relapsed (within the first year) and went on to 2L treatment. The remaining 27 patients had best response assessed prior to completion of 1LT. Brentuximab vedotin (19%) and GemOx (19%) were the most common 2L treatments. CONCLUSIONS This retrospective observational study describes treatment patterns and key clinical outcomes among patients receiving 1L PTCL treatment in France and the UK. CHOP-based regimens were used to treat 59.6% of the study patients. Understanding distribution of PTCL subtypes and outcomes of treatment in routine clinical practice is complementary to data derived from clinical trials and crucial to facilitate improvement of survival outcomes through the introduction of novel therapies for this challenging group of rare malignancies. Disclosures Fox: Janssen: Consultancy; Adienne: Other: Travel Support; Takeda Pharmaceuticals: Consultancy; Atara Biotherapeutics: Consultancy; AbbVie: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Sunesis: Consultancy. Ashaye:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd: Other: I am a paid employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd. Shah:Pfizer: Research Funding; Merck: Research Funding; Bayer: Research Funding. Dalal:Millennium Pharmaceuticals (Takeda): Other: I am a paid employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd. Truemper:Nordic Nanovector: Consultancy; Mundipharma: Research Funding; Janssen Oncology: Consultancy; Roche: Research Funding; Seattle Genetics, Inc.: Research Funding; Takeda: Consultancy, Research Funding.

Description: INTRODUCTION: Chronic myeloid leukemia (CML) is a bone marrow and blood disorder accounting for 15% of adult leukemia. Tyrosine kinase inhibitors (TKIs) have been the standard of care for CML treatment. However, an association between TKI use and cardiovascular events has been observed. Ponatinib and bosutinib are introduced to provide more options for patients who failed their first-line treatment. The incidence of major adverse cardiac events (MACEs), arterial occlusive events (AOEs), and venous occlusive events (VOEs) were assessed among CML patients who were prescribed ponatinib vs bosutinib. METHODS: A retrospective observational study was conducted among adult CML patients aged ≥18 years with use of 1 or 2 prior TKIs who were prescribed bosutinib or ponatinib. Study patients were selected from the IBM® MarketScan® Research database from July 2012-June 2017. The index date was defined as the index drug prescription date, identified based on TKI use during the identification period (January 2013-December 2016) in a hierarchical order based on the sequence of treatment lines: ponatinib and bosutinib without ponatinib. Continuous health plan enrollment for ≥6 months pre-index date (baseline period) and at least 6 months post-index date (follow-up period) was required. Cardiovascular (CV) events (MACEs, AOEs, VOEs) using ICD-9/10-CM diagnosis codes occurring through the earliest of index TKI discontinuation, switch to another TKI, or end of follow-up period, were calculated as the number of events per 100 person-years (PYs). Inverse probability of treatment weighting (IPTW) was applied to adjust for differences in baseline characteristics between the treatment cohorts. Kaplan-Meier (KM) and Cox proportional hazard model analyses were conducted on the adjusted sample to examine any difference in CV event risk. RESULTS: After applying the selection criteria, 79 and 109 patients were included in the ponatinib and bosutinib cohorts, respectively. Mean ages were 53 years (ponatinib cohort) and 58 years (bosutinib cohort). The average Charlson Comorbidity Index (CCI) scores - defined by categorizing comorbidities using diagnosis codes - were 1.23 for ponatinib and 1.81 for the bosutinib cohort. Common baseline comorbid conditions included anemia (ponatinib: 49%; bosutinib 34%), hypertension (ponatinib: 33%, bosutinib: 46%), and diabetes (ponatinib: 15%; bosutinib: 29%). Some patients were observed to have CV events, specifically MACEs (ponatinib 8%; bosutinib 16%) and AOEs (ponatinib 15%; bosutinib 28%), before index ponatinib or bosutinib use. In the follow-up period, ponatinib patients were associated with a similar incidence of MACEs (14.70 vs 10.46 per 100 PYs; p=0.464), AOEs (29.56 vs 34.50 per 100 PYs; p=0.632), and VOEs (36.21 vs 34.70 per 100 PYs; p=0.890) compared to bosutinib patients. After applying IPTW, similar risks of the CV events (MACE, AOEs, VTEs) were observed in the KM analysis (Figure 1) expressed as time to CV event. After adjusting for additional confounders using Cox models, compared to those with bosutinib use, ponatinib patients were associated with similar rate of MACEs (Hazard Ratio [HR]: 1.02; 95% CI: 0.34, 3.01), AOEs (HR: 0.90; 95% CI: 0.43, 1.85), and VOEs (HR: 0.92; 95% CI: 0.44, 1.94). CONCLUSION: Among CML patients treated with ponatinib or bosutinib in second or third line, similar risks of cardiovascular events (MACE, AOEs, VTEs) were observed in the follow-up in this study in a community setting. Figure 1 Disclosures Levy: Takeda (Millennium Pharmaceuticals): Consultancy. Xie:STATinMED Research: Other: I am a paid employee of STATinMED Research which is a paid consultant to Takeda Pharmaceutical Corporation. . Wang:STATinMED Research: Other: I am a paid employee of STATinMED Research which is a paid consultant to Takeda Pharmaceutical Company. . Neumann:Millennium Pharmaceuticals (Takeda): Employment, Other: I am a paid employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd. Srivastava:Millennium Pharmaceuticals (Takeda): Other: I am a paid employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd. Naranjo:Millennium Pharmaceuticals (Takeda): Other: I am a paid employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd. Xu:Millennium Pharmaceuticals (Takeda): Other: I am a paid employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd. Zhang:STATinMED Research: Other: I am a paid employee of STATinMED Research which is a paid consultant to Takeda Pharmaceutical Corporation.. Dalal:Millennium Pharmaceuticals (Takeda): Other: I am a paid employee of Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Ltd.

Description: Introduction P-2001, a randomized phase 2 trial (NCT02610777), investigated the efficacy and safety of pevonedistat (P), the first small-molecule inhibitor of the NEDD8-activating enzyme, in combination with azacitidine (A) versus A alone in patients (pts) with higher-risk (Revised International Prognostic Scoring System risk 〉3, including intermediate [≥5% blasts], high, or very high risk) myelodysplastic syndromes (MDS)/chronic myelomonocytic leukemia (CMML), or low-blast acute myeloid leukemia (LB AML) naïve to hypomethylating agents. The P-2001 trial recently demonstrated median event-free survival of 21.0 vs 16.6 months (HR=0.665; P = .076), and overall response rates (complete remission [CR] + CR with incomplete blood count recovery [CRi] + partial response [PR] + hematologic improvement [HI]) of 71% (n=39/55) vs 60% (n=32/53) with P+A compared with A, respectively. Management of MDS can significantly impact quality of life, and measures of high-symptom burden have been associated with worse clinical outcomes. We set out to explore patient-reported outcomes (PRO) as an exploratory endpoint in the study. Methods The study randomized 120 pts (1:1) to receive P+A or A alone in 28-day treatment cycles. The European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire - core 30 items (QLQ-C30) was administered at the first day of each cycle, at the end of treatment (EOT) visit and post-EOT visits. Physical functioning (PF), fatigue (FA), dyspnea (DY) and global health status/quality of life (QL) were identified as key PRO concepts that deserved specific attention in this population. Analyses were carried out to explore the PRO data: description of available PRO data, longitudinal analyses of change in the key PRO scores with repeated measurement mixed models (RMMM), including comparison between treatment arms, and descriptive analysis of the key PRO scores after clinical response depending on the type of response (PR, CR, CRi, or HI), and before and after transformation to AML for pts with higher-risk MDS, independently from the treatment received. Results There were 112 pts in the PRO population (defined as all pts with a PRO assessment at baseline and at least 1 post-baseline); baseline demographics and disease characteristics are presented in Table 1. At least 90% of pts in the study had a PRO available at each cycle. As expected, the amount of available PRO data decreased over the study due to progression, death, or study discontinuations. The RMMMs of the PRO population did not show any statistically significant difference in the change over time in key QLQ-C30 scores (PF, QL, FA, and DY) between P+A versus A alone. Pts who experienced CR (P+A, 40%; A, 29%) showed a nonsignificant improvement in PF and QL, as well as a nonsignificant decrease of FA after CR than at baseline; no differences were noted in DY. Pts for whom best response was PR had less improvement in the key PROs than pts with CR, and those with HI did not show improvement compared with baseline. Among the 12 pts with higher-risk MDS/CMML progressing to AML during the study with available PRO data (P+A, n=4; A, n=8), 6 showed worsening in PF score (vs 2 improving), 6 showed worsening in QL score (vs 1 improving), 7 showed worsening in FA score (vs 1 improving), and 7 showed worsening in DY score (vs none improving). Conclusions Measurement of QL and symptom burden are integral clinical endpoints in assessing new treatments in higher-risk MDS/CMML and LB AML. There was no evidence to suggest that the addition of P to A led to change in the key PROs identified: QL, PF, FA and DY. Achievement of CR was associated with higher PRO scores compared with baseline independently of the treatment received, and progression to AML was associated with worsening QL scores. Additional analyses are planned with the P-2001 PRO data to further explore the impact of P on PROs by evaluating the impact of dropout during the study, comparing findings according to treatment arm, and better understanding the possible effect of adverse events on PROs. Disclosures Zeidner: AbbVie: Honoraria, Other: Independent Review Committee; Agios: Honoraria; AROG: Research Funding; AsystBio Laboratories: Consultancy; Sumitomo Dainippon Pharma Oncology, Inc.: Research Funding; Genentech: Honoraria; Daiichi Sankyo: Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Forty-Seven: Other: Travel Reimbursement, Research Funding; Merck: Research Funding; Pfizer: Honoraria; Takeda: Consultancy, Honoraria, Other: Travel Reimbursement, Research Funding. Mazerolle:Takeda Pharmaceutical Company: Other: Granted research funding to Modus Outcomes, my employer; Modus Outcomes: Current Employment. Bell:Millennium Pharmaceuticals, Inc.: Current Employment. Cain:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Faller:Phoenicia Biosciences: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Viracta Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment; Briacell Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Dalal:Millennium Pharmaceuticals Inc, a wholly owned subsidiary of Takeda Pharmaceutical International Company, Cambridge, MA: Current Employment, Current equity holder in private company. Regnault:Modus Outcomes: Current Employment. Fram:Teva: Current equity holder in publicly-traded company; Baxter: Current equity holder in publicly-traded company; Gilead: Current equity holder in publicly-traded company; Pfizer: Current equity holder in publicly-traded company; Bristol Myers Squibb: Current equity holder in publicly-traded company; Takeda: Current equity holder in publicly-traded company; Vertex Phamaceuticals: Patents & Royalties: Patent 10/728,114; Takeda Pharmaceuticals Intl. Co.: Consultancy, Current Employment; BeyondSpring Pharmaceuticals Inc.: Consultancy. OffLabel Disclosure: Pevonedistat is the first small molecule inhibitor of the neural precursor cell expressed, developmentally downregulated 8 (NEDD8)-activating enzyme (NAE)

Description: Background: Despite therapeutic advances in classical Hodgkin lymphoma (cHL), only half of patients with relapsed/refractory (R/R) cHL are cured with salvage chemotherapy followed by stem cell transplantation (SCT). Most studies to date have been undertaken in Europe or North America and data on treatment patterns and clinical outcomes from other regions are limited. We present the results from the B-CD30+ HOdgkin Lymphoma International Multi-center Retrospective Study of Treatment PractIces and OutComes (B-HOLISTIC), which assessed cHL treatment pathways, clinical outcomes and healthcare resource utilization across East Asia, Latin America, Middle East, South Africa, Australia and Russia (data as of 04 March 2020). Methods: Data were collected retrospectively for patients (≥18 years) diagnosed with stage IIB-IV cHL or R/R cHL between 01 January 2010 and 31 December 2013, until death or last follow-up (whichever occurred first) across 13 countries. Patients with initial diagnosis of cHL and subsequent progression to R/R cHL were included in both groups, provided R/R cHL was diagnosed within the study period. The primary endpoint was progression-free survival (PFS) in patients with R/R cHL. Secondary endpoints included overall survival (OS), best clinical response, and adverse events (AEs). Results: In total, 1703 patients were enrolled from East Asia (n=426), Latin America (n=366), Middle East and South Africa (n=694), Australia (n=56) and Russia (n=161): 1598 and 426 patients were eligible for the cHL and R/R cHL groups (321 patients in the cHL group progressed to R/R cHL and were included in both groups). Median study follow-up was 65.2 and 53.2 months for the cHL and R/R cHL groups. Baseline patient characteristics are shown in Table 1. All patients in the cHL group received first-line chemotherapy: the most common regimens were ABVD (1363/1598; 85.3%) and BEACOPP (104/1598; 6.5%). First-line radiotherapy was given to 357/1598 (22.3%) patients in the cHL group. For R/R cHL, intensive chemotherapy was used as first-line salvage in 372/426 (87.3%) patients: the most common regimens were ESHAP (98/372; 26.3%) and DHAP (65/372; 17.5%), with an overall response rate of 62.0% (complete remission in 30.8% and partial remission in 31.2%). Of the 426 patients with R/R cHL, 292 (68.5%) were eligible for SCT at relapse/refractory diagnosis; 10 patients who were initially ineligible for SCT subsequently became eligible. In total, 222/302 (73.5%) eligible patients underwent SCT; 63/222 (28.4%) patients relapsed after SCT. Median PFS (95% CI) for the R/R cHL group was 13.2 (9.9-20.2) months following initial therapy (Figure 1), with estimated 1-, 3- and 5-year PFS rates of 51.2%, 38.7%, and 33.9%, respectively (Table 2). Median PFS was not reached for the first-line cHL group. Factors for PFS in the R/R cHL group are shown in Table 3. Median OS was not reached for both groups. All-cause, any grade AEs were reported by 783/1598 (49.0%) patients with cHL and by 233/426 (54.7%) patients with R/R cHL. Serious AEs were reported by 303/1598 (19.0%) patients with cHL and by 103/426 (24.2%) patients with R/R cHL: the most common (≥2.0%) were febrile neutropenia, pneumonia and pyrexia for cHL, and febrile neutropenia and pyrexia for R/R cHL. Conclusion: Results from B-HOLISTIC show that PFS rates remain low in patients with R/R cHL receiving salvage therapy; the greatest risk was among patients with inadequate response to salvage chemotherapy. The low PFS rates highlight the importance of considering novel targeted therapies to address unmet medical needs. PFS rates in patients with cHL were comparable with previous studies from Italy, Spain, and Israel (Avigdor A et al. EHA 2020) and the ECHELON-1 study (Bartlett NL et al. ASH 2019). The higher OS rates compared to PFS rates may be related to the effect of modern salvage regimens. Approximately half of patients with R/R cHL underwent SCT which may support the use of targeted therapies. Overall, these results from 2010-2013 show that despite the differences in healthcare systems, ethnicities and treatment patterns in B-HOLISTIC, clinical outcomes remain consistent. The authors note that given that the management of high-risk cHL has changed dramatically since 2013, further investigation in diagnostic criteria, response assessment and treatment patterns is needed. Study support: Data analysis (IQVIA) and medical writing (Synergy Vision) funded by Takeda Pharmaceuticals. Disclosures Ferhanoglu: Takeda: Other: Advisory Board; Abbvie: Other: Advisory Board; Roche: Other: Advisory Board; Janssen: Other: Advisory Board. Kim:Novartis: Consultancy; AstraZeneca and Korea Health Industry Development Institute: Research Funding; Sanofi: Consultancy; F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy; Voronoi: Consultancy; Boryung: Consultancy; AstraZeneca: Consultancy; Takeda: Consultancy. Karduss:Takeda: Honoraria. Rivas-Vera:Takeda: Current Employment, Other: Steering Committee in Clinical Research; Roche: Consultancy. Lim:National Cancer Centre Singapore: Current Employment. Yeh:AbbVie: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Astex: Membership on an entity's Board of Directors or advisory committees. Abdillah:Takeda: Current Employment. Huang:Takeda: Current Employment. Dalal:Takeda: Current Employment, Current equity holder in publicly-traded company. Wan:Takeda: Current Employment. Hertzberg:Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support; Gilead: Membership on an entity's Board of Directors or advisory committees; MSD: Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria; BMS: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees.