ALBERT

Description: Abstract 3641 Background: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of lymphoproliferative disorders, and most subtypes have a poor prognosis even with aggressive chemotherapy. Romidepsin is a potent class 1 histone deacetylase inhibitor approved by the US Food and Drug Administration for treatment of patients with PTCL who have received at least 1 prior therapy and patients with cutaneous T-cell lymphoma who have received at least 1 prior systemic therapy. A phase 2, single-arm, open-label registration study (GPI-06–0002) demonstrated the clinical benefit and tolerability of romidepsin in patients with relapsed or refractory PTCL (data cutoff: Oct 2010). Here, we present an update of the efficacy of GPI-06–0002 and characterize patients who achieved long-term responses (≥ 12 months) as of Dec 2011 (median follow-up: 22.3 months). Methods: Patients with histologically confirmed PTCL (N = 130) who failed or were refractory to ≥ 1 prior systemic therapy received romidepsin 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days for up to 6 cycles; treatment could be extended for responding patients. The primary endpoint was confirmed/unconfirmed complete response (CR/CRu) determined by an independent review committee (IRC) based on the International Workshop Response Criteria. Secondary endpoints included objective response rate (ORR: CR/CRu + partial response), duration of response (DOR), and time to progression. Disease response was assessed every 2 treatment cycles. Baseline patient characteristics by DOR (≥ 12 months vs 〈 12 months) were examined. Results: The majority of the 130 patients had stage III or IV disease (70%); 28% had bone marrow involvement. PTCL not otherwise specified (53%) and angioimmunoblastic T-cell lymphoma (21%) were the most common subtypes. Patients received a median of 2 prior systemic therapies (range, 1–8); 38% of patients were refractory to their last line of therapy. The ORR was 25% (33 of 130 patients), including CR/CRu in 15% (19 of 130) of patients. The median duration of objective response was 28 months, with the longest response ongoing at 48 months (Figure). Of the 19 patients who achieved CR/CRu, 13 (68%) had not experienced disease progression per the IRC at a median follow-up of 25.8 months. The median duration of CR had not yet been reached (range, 1–48+ months; Figure). Of the 19 patients who achieved CR/CRu, 10 were long-term responders (responses ≥ 12 months). Interestingly, heavy pretreatment (≥ 4 prior systemic therapies) did not preclude patients from achieving long-term CR/CRu: 5 of 10 patients (50%) who maintained CR/CRu for ≥ 12 months were heavily pretreated vs 1 of 9 (11%) patients with CR/CRu maintained for 〈 12 months. Long-term CR/CRu was achieved regardless of response to last prior therapy; only 2 of 10 (20%) long-term responders had an objective response on their last treatment. In contrast, 6 of 9 (67%) patients with CR/CRu for 〈 12 months responded to their last prior therapy. Furthermore, advanced disease did not preclude long-term response to romidepsin: all 10 patients (100%) who maintained CR/CRu for ≥ 12 months had stage III/IV disease vs 55.5% of those who maintained CR/CRu for 〈 12 months. Other characteristics, such as Eastern Cooperative Oncology Group performance status, International Prognostic Index score, age, sex, and race, were similar among patients achieving CR/CRu for ≥ 12 months or 〈 12 months. Conclusions: Single-agent romidepsin induced durable responses in patients with relapsed/refractory PTCL, with responses ongoing at 48 months. None of the examined patient and disease characteristics predicted failure to achieve long-term remissions. These results support the use of romidepsin in relapsed/refractory PTCL. Disclosures: Coiffier: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Pro:Allos: Honoraria; Spectrum : Honoraria; Seattle Genetics : Research Funding; Celgene: Honoraria, Research Funding. Prince:Celgene : Consultancy, Honoraria, Research Funding. Foss:Celgene : Consultancy. Sokol:Celgene : Honoraria, Speakers Bureau. Morschhauser:Celgene : Consultancy, Honoraria. Pinter-Brown:Celgene : Consultancy; Allos : Consultancy. Shustov:Celgene : Honoraria, Research Funding, Speakers Bureau. Nielsen:Celgene: Employment, Equity Ownership. Nichols:Celgene: Consultancy, Employment, Equity Ownership. Horwitz:Celgene: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy; Bristol-Myers Squibb: Consultancy; Allos: Consultancy, Research Funding; Genzyme: Consultancy; Johnson & Johnson: Consultancy; Infinity Pharmaceuticals: Research Funding; Seattle Genetics: Consultancy, Research Funding.

Description: Abstract 3820 Background: While patients with sickle cell disease (SCD) visit emergency departments (ED) in rates leading to a significant health system burden, limited comprehensive evaluations of utilization patterns have been published using data connecting visits to patients across facilities. Purpose: This study aims to examine sociodemographic predictors of ED utilization in SCD. Methods: This retrospective cohort study employed 2007 data from the California Office of Statewide Health Planning and Development (OSHPD). Data included all inpatient and ED discharges from all non-federal California hospitals; identifiers connected each visit to an individual patient, across all facilities in the state. Primary predictors of interest included age, insurance status and distance to the nearest source of comprehensive SCD care. Additional influential variables included disease severity, urbanicity, gender, race, and ethnicity. Geographic Information Systems software and social networking methods were used to derive a measure of distance from patient residence to the nearest self-identified SCD comprehensive care provider. Multivariate regression techniques evaluated sociodemographic predictors of utilization while also adjusting for confounding variables. Results: In 2007, 2,920 California SCD patients made 16,364 ED visits. Adults ≥ 21 had higher ED visit rates than children and were more likely to both be in the highest tier of users and visit multiple facilities. Patients living further from the nearest source of a self-identified provider of comprehensive SCD care had higher ED visit rates with a lower likelihood of inpatient admission from the ED. Publicly insured patients had higher ED visit rates and were more likely to be in the highest tier of users than were the privately insured or uninsured. Conclusions: Age ≥ 21, distance from comprehensive SCD care, and insurance status are significant predictors of ED utilization in SCD. As a routine source of care decreases ED utilization, these findings prompt concern that these factors act as barriers to accessing comprehensive SCD care. Disclosures: No relevant conflicts of interest to declare.

Description: Background: AYA (15-39y) diagnosed with hematologic malignancies have inferior survival and have not seen the same survival improvement in comparison with those diagnosed during childhood (0-14y) leaving an AYA Gap. Treatment on pediatric trials is associated with superior survival in 15-21y diagnosed with acute lymphoblastic leukemia (ALL). However, impact of care at National Cancer Institute-designated Comprehensive Cancer Centers (NCICCC) for AYA of all ages or Children’s Oncology Group sites (COG) for AYA aged 15-21y remains unstudied. Methods: We constructed a population-based cohort of 1,388 children (1-14y), 673 young AYA (15-21y) and 2,275 older AYA (22-39y) with newly diagnosed ALL, acute myeloid leukemia (AML), Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) reported to the LA County cancer registry between 1998-2008. We sought to determine the impact of care at NCICCC/COG (NCICCC+COG: n=3, COG: n=3) on overall survival (OS) and barriers to access to care at NCICCC/COG in AYA with hematologic malignancies. Multivariable Cox regression was used to derive hazard ratios (HR) for mortality, adjusting for gender, race/ethnicity, socioeconomic status (SES) [and stage in lymphomas]. Multivariable logistic regression was used to derive odds ratios (OR) for likelihood of care at NCICCC/COG, adjusting for above variables plus insurance and distance to the nearest NCICCC/COG. Distance to NCICCC/COG was derived using Geographic Information Systems. Results: AYA experienced inferior 5y OS as compared to children across diagnoses (Figure: ALL [n=1,380]: 72% [10-14y] vs 44% [15-21y] vs 38% [22-39y], p

Description: Background: AITL is a common subtype of peripheral T-cell lymphoma (PTCL) that typically presents with lymphadenopathy and extranodal disease and is associated with frequent infections due to immune dysregulation. Patients with AITL generally have a poor prognosis, even with aggressive chemotherapy. Romidepsin is a structurally unique, potent, bicyclic, class 1 selective histone deacetylase inhibitor approved by the US Food and Drug Administration for the treatment of patients with PTCL who have received at least 1 prior therapy and patients with cutaneous T-cell lymphoma who have received at least 1 prior systemic therapy. A phase 2, single-arm, open-label registration study (GPI-06-0002) demonstrated durable clinical benefit and long-term tolerability of romidepsin in patients with relapsed or refractory PTCL. Here, we present updated data for patients with AITL from GPI-06-0002. Methods: Patients with histologically confirmed PTCL (N = 130) who experienced failure with or were refractory to ≥ 1 prior systemic therapy received romidepsin 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days for up to 6 cycles; treatment could be extended for patients with stable disease (SD) or response. The protocol was amended to allow for (but not mandate) maintenance dosing of twice per cycle for patients treated for ≥ 12 cycles; dosing could be further reduced to once per cycle at ≥ 24 cycles in patients who had received maintenance dosing for ≥ 6 months. The primary endpoint was the rate of confirmed/unconfirmed complete response (CR/CRu) as determined by an independent review committee based on International Working Group criteria. Secondary endpoints included objective response rate (ORR: CR/CRu + partial response [PR]), duration of response (DOR), and time to progression; progression-free survival and overall survival (OS) were also assessed. Disease response was assessed every 2 treatment cycles. The analysis herein is focused on updated data (median follow-up, 22.3 months) in patients with AITL. Results: Of 27 patients with AITL, most had advanced disease (96% stage III/IV; 44% with bone marrow involvement; 52% with elevated lactate dehydrogenase) and heavy pretreatment (median, 2 [range, 1-8] prior therapies) and 37% were refractory to their last line of therapy. The ORR for patients with AITL was 33% (9 of 27 patients), with most responders achieving CR/CRu (6 of 27 patients; 22%). Most responses were noted at the first response assessment, with a median time to response of 52 days. Furthermore, an additional 8 patients with AITL achieved SD (30%), 3 of whom had disease stabilization for ≥ 90 days. The median DOR has not been reached, with the longest response ongoing at 56 months (Figure). Five patients with AITL and DOR of ≥ 12 months with romidepsin had either 1 (n = 2) or 2 (n = 3) prior therapies, and 3 of the 5 were refractory to their last line of therapy (CHOP [cyclophosphamide, doxorubicin, vincristine, prednisone], GVD [gemcitabine, vinorelbine, doxorubicin], or pralatrexate). All 5 responding patients who remained on treatment for ≥ 12 cycles received maintenance dosing of twice per cycle. Dosing for the 3 patients with the most durable responses was also later amended to 1 dose per cycle. For all patients with AITL treated with romidepsin, the median OS was 18 months (range, 2-58 months). Grade 3/4 infections (all types pooled, regardless of relationship to study drug) were reported in 6 patients (22%), and no discontinuations due to infection occurred. Conclusions: Single-agent romidepsin induced rapid, complete, and durable responses in some patients with relapsed/refractory AITL, with several responses ongoing for 〉 3 years. Patients with long-term responses to romidepsin received maintenance dosing. These results support the use of romidepsin in relapsed/refractory AITL. Figure. Patients With AITL Who Achieved a Response to Romidepsin Figure. Patients With AITL Who Achieved a Response to Romidepsin Disclosures Pro: Celgene: Honoraria. Horwitz:Bristol Myers Squibb,: Consultancy; Amgen: Consultancy; Spectrum: Research Funding; Seattle Genetics: Consultancy, Research Funding; Kiowa Kirin: Research Funding; Infinity: Research Funding; Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Jannsen: Consultancy. Prince:Celgene: Honoraria, Research Funding. Foss:Celgene: Consultancy, Research Funding, Speakers Bureau. Sokol:Celgene: Consultancy. Morschhauser:Spectrum: Honoraria; Bayer: Honoraria; Mundipharma: Honoraria; Genentech: Honoraria; Gilead: Honoraria. Pinter-Brown:Celgene: Consultancy. Padmanabhan Iyer:Janssen Biotech, Inc.: Honoraria; Celgene: Speakers Bureau; Houston Methodist Cancer Center: Employment. Shustov:Celgene: Consultancy, Honoraria, Research Funding. Balser:Celgene: Consultancy. Coiffier:Celgene: Honoraria.

Description: Abstract 2480 Poster Board II-457 Introduction: As young adults with Sickle Cell Disease (SCD) age out of comprehensive pediatric coverage, they are left with suboptimal coverage for disease-appropriate comprehensive care, and rely on Emergency Departments (ED). This situation is implied to affect SCD outcome, as review of death certificates suggests that patients cared for outside comprehensive sickle cell centers (CSCC) die earlier on average than patients cared for within CSCCs. Los Angeles County (LAC) poses particular challenges, as even within the CSCC network patients die younger than the national average. There are no data describing LAC SCD patients outside of the tertiary care referral centers, nor are there population-based data describing the effect of access to health care on ED utilization in SCD. In order to eliminate these disparities in health care and health outcomes, the first step is to identify the population and where they receive care. This population-based study assesses the effect of where a patient lives, age, and insurance status on utilization of emergency departments (ED) and rates of inpatient admission. Methods: We conducted a retrospective cohort study using the 2007 LAC data from the California Office of Statewide Healthcare Planning and Development, with all hospital discharges from non-federal emergency departments (ED) and inpatient units. We selected patients based on ICD9 codes indicating SCD (282.60-282.69) or SB-thalassemia (282.41-282.42) as a primary or secondary diagnosis. Unique identifiers longitudinally link multiple visits. One of the 8 service planning areas (SPA) defined by LAC Department of Public Health has very poor health outcomes and access to care as compared to the others. Using Poisson regression, we evaluated the effect of living in this resource-poor SPA on the number of SCD-related ED visits per year. We controlled for age (adult ≥21 years old vs. child), gender (male vs. female), race (African American vs. not), ethnicity (Hispanic vs. not), and socioeconomic status (using insurance as a proxy). Finally, we evaluated the effect of living in the resource-poor SPA on disposition from the ED (admit vs. discharge) using binary logistic regression. Results: In LAC in 2007, 1088 identified individual patients with SCD visited the ED, leading to 4420 total ED visits. There were 298 children and 790 adults (〉21yo). The mean number of visits per patient was 4.06 (SD = 10.84; range 1 to 180). The mean number of annual SCD-related ED visits per hospital was 35.93 (SD = 75.30; range 1 to 414). Children accounted for 18% of the visits and adults 82%. SCD adults had 2 times the rate of ED visits as compared to children. Patients living in the poor-resource SPA had 7% more ED visits than those living in the SPAs with better healthcare resources. Publicly insured SCD patients had a 33% higher rate of ED visits than privately insured patients and a 77% higher rate of visits than self-pay patients. Being male and African American were also significantly associated with an increased rate of ED visits. ED visits by patients from the resource-poor SPA were 13% less likely to result in an inpatient admission than were the ED visits by patients living in the other SPAs. Being female, African American, Hispanic, and having public insurance were also significantly associated with increased likelihood of the ED visit resulting in inpatient admission. Conclusions: Our data suggest that among SCD patients in LAC, adults ≥ 21 years of age, those living in a resource-poor area of LAC, and the publicly insured all have higher ED utilization rates. ED visits by patients from the resource-poor area of LAC are less likely to result in inpatient admissions whereas visits from publicly insured patients were more likely to result in an inpatient admission. The dramatically higher rate of ED visits by those 21 and over is consistent with the notion that adults with SCD have poor access to appropriate comprehensive care leading them to seek care in the ED. The results also support the premise that poor access to health care and public insurance are associated with suboptimal comprehensive care in SCD, leading to a higher rate of ED use. Considering LAC's population size and diversity, this population-based study substantiates findings from the tertiary care center cohorts. These findings beg further investigation into the outpatient utilization practices of patients with SCD as a means of developing measures of access to care in SCD. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 253 Introduction: Acute chest syndrome (ACS) is a leading cause of morbidity and mortality in patients with Sickle Cell Disease (SCD). Although the NIH recommends transfusion as standard of care therapy for this diagnosis, practice patterns vary. In 2000, the National Acute Chest Study group found that 72% of patients with ACS were transfused. This study, which was perfomed at academic medical centers with sickle cell treatment programs, used specific diagnostic inclusion criteria. As ACS may be difficult to distinguish from pneumonia, recognition and treatment of the diagnosis may vary by hospital and by presence or absence of a sickle cell specialist. With access to hospital discharge data from all California hospitals seeing SCD patients, we aimed to describe transfusion practices in ACS. Methods: This retrospective cohort study uses 2005–2008 public data from the California Office of Statewide Health Planning and Development (OSHPD). Data included all inpatient and emergency department (ED) discharges from all non-federal California hospitals. Cases were selected based on discharge from or admission via an ED and the presence of a sickle cell disease ICD-9 code in the primary or a secondary diagnosis (282.60-282.69, 282.41–282.42). Further inclusion criteria included presence of ACS (517.3) or respiratory diagnoses including pneumonia, pulmonary edema, acute respiratory distress syndrome, hypoxia and respiratory failure in any primary or secondary diagnosis. Frequency of transfusion, intubation and mortality were described and chi-square tests were performed to determine the statistical significance of differences between groups of patients treated with or without transfusion as well as between groups of adults and children. Results: Between 2005–2008, 4306 ED visits by Californians with SCD were associated with either ACS or a related respiratory diagnosis and only 42.5% of these cases were associated with transfusion. Limiting the diagnosis to ACS only, 1399 cases were identified, and still only 50.4% of these cases were associated with transfusion. Among patients with ACS or a related diagnosis, the majority were admitted to the hospital (90.9%); only 59.2% of intubated cases (n=238) were transfused; and of the 92 deaths during this period, only 46.7% were associated with transfusion. Patients who were 18 and over were transfused more often than young children (43.2% vs. 35.7%; 2(1)=12.37, p

Description: Background: Lymphadenopathy is a common pediatric problem that pediatricians and general practitioners face in their clinic. Although typically found in the setting of an infection and benign in nature, referrals to a Pediatric Hematologist/Oncologist are sometimes made to evaluate for hematologic malignancy. The associated health care costs and potential psychological impact on family members as a result of making a referral to a hematology/oncology specialist warrants consideration. To better understand the outcomes of patients with lymphadenopathy and provide evidence based recommendations for need for referral, we have conducted a retrospective chart review to assess clinical features as risk markers for malignancy among patients referred for lymphadenopathy. Methods: We conducted a retrospective chart review of 1,164 patients referred to the Division of Pediatric Hematology Oncology at Children's of Alabama over a four year period (2013-2016). The diagnosis and demographics were recorded for every patient. Location of lymphadenopathy (cervical, supraclavicular, axillary, abdominal, inguinal, and mediastinal) and size of lymph nodes on exam and imaging were recorded. Symptomatology (fever, night sweats, weight loss, fatigue, bone pain, shortness of breath, and bleeding symptoms) and laboratory findings, such as white blood cell (WBC), Hemoglobin, Platelet count, lactate dehydrogenase (LDH), uric acid, and erythrocyte sedimentation rate (ESR) were recorded. Descriptive statistics, Student's t-test, and Wilcoxon signed-rank test were conducted using JMP® 12. Sensitivity and specificity were calculated using a conventional two-by-two table (2x2). Results: Among 1,164 patients that were referred to Pediatric Hematology Oncology, sixty nine (5.9%) were referred for lymphadenopathy. Sixty one (88.5%) out of sixty nine patients presented to our clinic for evaluation. Thirteen patients (21%) were diagnosed with malignancy (11 lymphoma, 2 leukemia). While all patients in this cohort were referred for concern of enlarged lymph nodes (lymphadenopathy) by their primary physician, we assessed the sensitivity and specificity of utilizing a cut-off of ≥ 2cm assessed by physical exam or imaging to define a population with "abnormal lymphadenopathy". In total 32 patients met this criteria for abnormal lymphadenopathy. All 13 patients who ultimately were diagnosed with a malignancy by biopsy met this size criteria for abnormal lymphadenopathy in at least one location (sensitivity 100%). Nineteen of 42 patients without malignancy were noted to have abnormal lymphadenopathy in at least one location (specificity 55%). The mean age of patients with lymphadenopathy was 9.49 years. Older patients were more likely to have a diagnosis of malignancy (13.61 years vs. 8.38 years, p=0.0034). Mean months of lymphadenopathy was 8.2 months. No statistical difference was noted between months of lymphadenopathy present and diagnosis of malignancy (p=0.56). Patients with malignancy had a significantly higher WBC (43.5 10*3/ µL vs. 27.6 10*3/ µL, z = 2.84, p=0.0044) than patients without malignancy. No statistical differences were noted for patients with and without malignancy for hemoglobin (p=0.9), platelet count (p=0.7), LDH (p=0.2), uric acid (p=0.5), or ESR (p=0.7). None of the symptomatology parameters demonstrated a sensitivity greater than 60%. Conclusion: Lymphadenopathy is a common pediatric problem in the outpatient setting that may require referral to a Pediatric Hematologist/Oncologist to evaluate for malignancy. Our data suggests that lymphadenopathy≥2cm in at least one location either by physical exam or imaging is highly sensitive for malignancy. Thus, pediatricians and general practitioners should consider continued monitoring and conservative management of patients with lymphadenopathy

Description: BACKGROUND: AYAs (15-39y) with ALL have poor survival compared to children (1-14y). Placement on pediatric vs. adult clinical trials has been implicated in these differences, but a more comprehensive approach (sociodemographics, clinical prognostic factors, treatment provider/ intensity) is lacking and needs to be examined in the real world environment. We address this gap by evaluating factors contributing to the inferior outcome in AYA at a granular level. METHODS: The study included242 patients diagnosed with ALL between 1990 and 2010 at age 1-39y and treated at a comprehensive cancer center (irrespective of enrollment on clinical trial). Medical record abstraction yielded the following: Sociodemographics: payor, race/ethnicity, socioeconomic status (SES); Clinical Prognosticators: WBC at diagnosis (100K 27% vs. 20%, p=0.2; median time to remission: 31d vs. 31d, p=0.91). However, AYAs received fewer months of maintenance therapy than children (median=14.9m vs 24.8m, p

Description: Background PTCL is a heterogeneous group of mature, post-thymic, T- and natural killer–cell disorders associated with a poor prognosis in most subtypes. Anthracycline-based therapies (eg, CHOP) are most often used in the frontline treatment of PTCL, although they do not typically lead to durable remissions. Older patients may not be eligible for additional chemotherapeutic regimens due to comorbidities and/or poor performance status. Thus, it is important to identify appropriate treatment strategies for older patients with PTCL, particularly in the salvage setting. Romidepsin is a potent class I histone deacetylase inhibitor approved by the FDA for the treatment of patients with PTCL who have received ≥ 1 prior therapy and patients with cutaneous T-cell lymphoma who have received ≥ 1 prior systemic therapy. Approval of PTCL was based on results from the pivotal study of romidepsin for the treatment of relapsed/refractory PTCL (N = 131) that demonstrated durable clinical benefit and tolerability and was supported by a similar study from the National Cancer Institute (N = 47). The objective herein is to present efficacy and safety data for romidepsin specific to older patients (≥ 60 years) with relapsed/refractory PTCL in the pivotal and supportive trials. Methods In both trials, patients with PTCL who relapsed from or were refractory to ≥ 1 prior systemic therapy received romidepsin 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 of 28-day cycles. For the pivotal trial, the primary endpoint was confirmed/unconfirmed complete response (CR/CRu) determined by an independent review committee. For the supportive trial, the primary endpoints were objective response rate (ORR) and rate of CR by investigator assessment. In this analysis, efficacy and safety data for patients ≥ 60 years old were examined and compared with those for the overall study population. Results In the pivotal study, the overall median age was 61 years (range, 20-83); 71/130 patients (55%) were ≥ 60 years old (median 67 years [range, 60-83]) with a median of 2 prior systemic therapies (range, 1-8), including prior stem cell transplant in 7 patients. Response rates in the older population were similar to those seen overall: 25% ORR for both populations, including 14% and 15% with CR/CRu for older vs overall populations, respectively. Also, in both the older and overall populations, the median DOR was 28 months, with the longest response ongoing at 48 months (median follow-up 22.3 months). Of the 10 older patients who achieved CR/CRu, 6 had a DOR of ≥ 12 months. Survival was also similar, with 5 and 4 months PFS and 12 and 11 months OS for the older vs overall populations, respectively. In the supportive trial, the overall median age was 60 (range, 27-84); 23/47 patients (49%) were ≥ 60 years old (median 68 years [range, 61-84]) with a median of 2 prior regimens (range, 1-8), including prior stem cell transplant in 7 patients. Response rates in the older population were similar to those seen overall: 32% and 38% ORR, including 14% and 18% with CR, respectively. The median DOR was 5 months (range, 3-49) and 9 months (range, 2-74+) for the older vs overall populations, respectively. One 79-year-old patient with 6 prior systemic therapies achieved CR on romidepsin and stopped therapy after 6 cycles in consideration of his age. Off therapy, disease progression was observed; romidepsin was restarted per protocol and patient achieved a second CR, receiving an additional 22 cycles of therapy. In both the pivotal and supportive trials, rates of grade ≥ 3 adverse events were similar for the overall vs older patient populations (Table). Conclusions In phase 2 trials of romidepsin for the treatment of relapsed/refractory PTCL, patients aged ≥ 60 years comprised approximately half of patients. Both efficacy and safety were similar for the older vs overall populations. Thus, data were not skewed due to age, and romidepsin is suitable for use in elderly patients with relapsed/refractory PTCL. Disclosures: Shustov: Celgene Corporation: Honoraria, Research Funding, Speakers Bureau. Coiffier:Celgene Corporation: Consultancy; Spectrum Pharmaceuticals: Consultancy. Horwitz:Celgene Corporation: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy, Research Funding; Seattle Gen: Consultancy, Research Funding; Infinity Pharmaceuticals: Research Funding; Kyowa Hakko Kirin Pharma: Research Funding; Millenium: Consultancy, Research Funding; Genzyme: Consultancy; Janssen: Consultancy. Sokol:Celgene Corporation: Consultancy, Speakers Bureau; Gloucester: Research Funding. Pro:Celgene Corporation: Honoraria. Nielsen:Celgene Corporation: Employment, Equity Ownership. Balser:Celgene Corporation: Consultancy. Prince:Celgene Corporation: Honoraria, Research Funding. Allen:Celgene Corporation: Honoraria. Bates:Celgene Corporation: Research Funding.

Description: Abstract 2680 Background: Romidepsin is a class 1 selective histone deacetylase (HDAC) inhibitor approved in the United States for patients with relapsed/refractory cutaneous and peripheral T-cell lymphomas. Potential cardiac class effects of HDAC inhibitors have been variably reported. We have previously reported that detailed electrocardiogram (ECG) analyses from 110 patients across 3 clinical studies showed clinically insignificant, transient ECG changes that were not associated with functional cardiovascular changes. The primary objective of the study described herein was to further evaluate the potential of romidepsin to prolong QT and assess any possible relationship between romidepsin plasma concentration and heart rate-corrected QT interval duration (QTc). Methods: Patients from GPI-06–0005, an exploratory phase 1 study of adult patients with advanced malignancies treated with 1-hour or 4-hour intravenous (IV) romidepsin infusion, received ECG assessments on Day 1 of cycles 1 and 2: baseline (both pre- and post-antiemetic premedication) and at each pharmacokinetic (PK) sampling time (0.25, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours after initiation of romidepsin dosing). Patients either received a 4-hour IV infusion at 14 mg/m2 on Days 1, 8, and 15 of each 28-day cycle for 6 cycles or for 1 cycle followed by 8–12 mg/m2 infused over 1 hour for 5 cycles. Post-antiemetic baseline was included to isolate the effects of romidepsin as antiemetics alone may increase the QTc interval. All ECGs were read by a central ECG laboratory and overread by a cardiologist for verification of interval measurements. Standard analyses as defined in the International Conference on Harmonization E14 Guidance, Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs were used. Nonlinear mixed effect modeling was used to analyze the exposure-response relationship of romidepsin and QTc. Results: ECG data were available for 26 patients who received romidepsin at 14 mg/m2 over a 4-hour IV infusion (approved dosing regimen). Fourteen of these patients also received 8–12 mg/m2 romidepsin over a 1-hour IV infusion; 3 patients received 8 mg/m2, 6 received 10 mg/m2, and 5 received 12 mg/m2. The majority of the 26 patients were female (62%) and White (89%); median age was 61.7 years (range, 44–82 years). Patients who received romidepsin at 12 mg/m2 as a 1-hour infusion had a median plasma Cmax up to 2.5-fold higher than that observed with the approved dosing regimen. The time courses of mean QTcF (Fridericia correction), QTcI (individual correction) and ΔQTcF, as well as median romidepsin plasma concentration were examined. No marked trend was evident, except for some evidence of a modest change in QTcF that was temporally dissociated from the pharmacokinetic profile. However, no consistent pattern of pharmacodynamic counterclockwise hysteresis was noted across or within patients. Exposure-response modeling demonstrated no statistically significant effect of romidepsin concentration on QTc. As shown in the Figure comparing change in QTcF relative to baseline pre-antiemetic administration or post-antiemetic administration, there was a slight mean decrease from post-antiemetic baseline in QTcF at each time point following romidepsin administration, and a mean increase relative to pre-antiemetic baseline. Mean changes in QTcF from the post-antiemetic, pre-romidepsin baseline for the 14 mg/m2 4-hour infusion were negative for all assessments. The maximum upper bound of the 90% confidence interval (CI) for the change from post-antiemetic, pre-romidepsin baseline was 5.59 ms noted at the 6-hour time point; mean change in QTcF at this time was –0.11 ms. No patients in this study developed a QTcF 〉 450 ms in the 24-hour period following the start of infusion. No trends were observed across lower dose levels (8-, 10-, and 12-mg/m2) for the 1-hour romidepsin infusions. Conclusions: No concentration-dependent effects of romidepsin on the duration of QTc interval were identified, including at romidepsin exposures up to more than 2.5-fold higher than the approved and clinically used dosing of 14 mg/m2 as a 4-hour IV infusion. Disclosures: Godfrey: Geron Corporation: Consultancy; Neurocrine Biosciences: Consultancy; Agios: Consultancy; Adnexus: Consultancy; Lundbeck, Inc.: Consultancy; Vertex Pharmaceuticals: Equity Ownership; Anoixis Corporation: Employment; Celgene: Consultancy. Off Label Use: Dosing in studies is off label. Cabell:Celgene: Consultancy. Balser:Celgene: Contracted Consultancy. Wolfson:Celgene: Contracted Consultancy. Nichols:Celgene: Employment, Equity Ownership.