Search

When two small fluid drops are sufficiently close, the van der Waals force overcomes surface tension and deforms the surfaces into contact, initiating coalescence. The dynamics of surface deformation across an inviscid gap falls into two distinct regimes (Stokes and inertial–viscous) characterized by the forces that balance the van der Waals attraction at leading order (viscosity, and both inertia and viscosity). The previously studied Stokes regime holds for very viscous drops but fails for less viscous drops as inertia becomes significant before contact is reached. We show that the subsequent inertial–viscous dynamics is self-similar as contact is approached, with the gap width decreasing as $t{'^{3/8}}$ and the radial scale of the deformed region decreasing as $t{'^{1/2}}$ as $t{'}\to 0$ , for time until contact $t'$ . The self-similar behaviour is universal and is the generic asymptotic behaviour observed in time-dependent simulations. The unique self-similar gap profile of the inertial–viscous regime suggests new initial conditions for the coalescence of the drops after contact.

PURPOSE Standard cytotoxic induction chemotherapy for acute myeloid leukemia (AML) results in prolonged neutropenia and risk of infection. Romyelocel-L is a universal, allogeneic myeloid progenitor cell product being studied to reduce infection during induction chemotherapy. PATIENTS AND METHODS One hundred sixty-three patients with de novo AML (age ≥ 55 years) receiving induction chemotherapy were randomly assigned on day 0 (d0), of whom 120 were evaluable. Subjects received either romyelocel-L infusion on d9 with granulocyte colony-stimulating factor (G-CSF) starting daily d14 (treatment group) or G-CSF daily alone on d14 (control) until absolute neutrophil count recovery to 500/µL. End points included days in febrile episode, microbiologically defined infections, clinically diagnosed infection, and days in hospital. RESULTS Mean days in febrile episode was shorter in the treatment arm from d15 through d28 (2.36 v 3.90; P = .02). Similarly, a trend toward decreased microbiologically defined infections and clinically diagnosed infection in the treatment arm was observed from d9 to d28 (35.6% v 47.5%; P = .09), reaching a statistically significant difference from d15 to d28 (6.8% v 27.9%; P = .002). Because of this, antibacterial or antifungal use for treatment of an infection was significantly less in the treatment group (d9-d28: 44.1% v 63.9%; P = .01). Significantly fewer patients in the treatment arm received empiric antifungals from d9 tod28 (42.4% v 63.9%; P = .02) and d15-d28 (42.4% v 62.3%; P = .02). Patients in the treatment arm also had 3.2 fewer hospital days compared with control (25.5 v 28.7; P = .001). Remission rates and days to absolute neutrophil count recovery were similar in the two groups. No patients in the romyelocel-L plus G-CSF group died because of infection compared with two patients in the control arm. No graft-versus-host disease was observed. CONCLUSION Subjects receiving romyelocel-L showed a decreased incidence of infections, antimicrobial use, and hospitalization, suggesting that romyelocel-L may provide a new option to reduce infections in patients with AML undergoing induction therapy.

Background: Disparities driven by socioeconomic factors have been shown to impact outcomes for cancer patients. We sought to explore this relationship among patients with multiple myeloma (MM) who were not considered for hematopoietic stem cell transplant in the first-line setting and how it varied over time. Methods: We queried the National Cancer Database for patients diagnosed with MM between 2004 and 2016 and included only those who received systemic therapy as the first-line treatment. Enrollment rates for therapy were calculated as receipt of systemic therapy as the incident event of interest (numerator) over time to initiation of therapy (denominator) and used to calculate incident rate ratios that were further analyzed using Poisson regression analysis. A multivariate Cox proportional hazards model was constructed for survival analysis, and differences were reported as hazard ratios (HRs). Results: We identified 56,102 patients for enrollment analysis and 50,543 patients for survival analysis. Therapy enrollment in a multivariate model was significantly impacted by race and sex (p 1), whereas female sex, non-Hispanic black race, higher income, and treatment at an academic center were associated with improved survival (HR

Purpose: Oral mucositis (OM) is a common, debilitating complication of conditioning regimens for hematopoietic stem cell transplantation (HSCT). Supersaturated calcium phosphate rinse (SCPR) and palifermin have shown efficacy in preventing severe OM. However, whether their efficacy differs is unknown. We aimed to compare the efficacy of SCPR and palifermin in HSCT patients receiving myeloablative conditioning. Methods: A comprehensive review of our institutional database was performed to identify patients who received myeloablative-conditioning therapy over 5 years. Most patients received Fludarabine, Busulfan and total body irradiation (FBT). Results: We identified 26 patients who received SCPR and 122 patients who received palifermin for OM prophylaxis. The prevalence of World Health Organization (WHO) grade 3 or 4 OM was significantly lower in the palifermin group (57% vs 100%, p=0.01). In addition, the palifermin group had lower WHO grade 4 OM (22% vs 62%, p=0.0006). The overall prevalence of OM was not significantly different between the two groups (86% for palifermin group vs 100% for SCPR arm, p=0.15). Subgroup analyses demonstrated improved outcomes with palifermin, regardless of age, sex, disease status, donor type, and primary diagnosis. Conclusion: As compared to SCPR, the use of palifermin is associated reduced severity of OM in HSCT patients receiving radiotherapy-based myeloablative conditioning.

A minority of patients diagnosed with diffuse large B-cell lymphoma (DLBCL) undergo surgery before the initiation of systemic therapy. The aim of this study is to explore the characteristics of patients undergoing surgery prior to systemic therapy (surgfirst), the predictors for surgfirst, and the survival outcomes.The National Cancer Database was queried for patients with DLBCL diagnosed between 2006 and 2015, and we performed a subgroup analysis of patients that received surgfirst. Time-to-initial therapy (TTI) was defined as the time in days (d) from diagnosis to systemic therapy. Overall survival was measured from the day of diagnosis in terms of months (m).Factors associated with lower likelihood of surgfirst were non-Hispanic Black race (p-value0.005), rural location (p-value0.005), treatment at academic center (p-value0.005), Medicaid insurance (p-value=0.01), comorbidity score=3 (p-value 0.007), year of diagnosis, advanced stages of disease, and presence of B-symptoms. The TTI of systemic therapy was delayed in the surgfirst group - 34 (IQR 22-52) days vs. 23 (IQR 13-38) days, p-value0.005. The five-year overall survival was 62.7% (95% CI 62.1-63.2%) vs. 58.3% (95% CI 57.7-60.0%) - HR 0.87 (95% CI 0.85-0.89), p-value0.005. The factors associated with higher mortality were advanced comorbidities, lower educational status, disease primarily located in the bone, brain, and spinal cord, advanced clinical stage, presence of B-symptoms, and advanced age.Despite the delay in systemic therapy, we could not identify a detrimental impact of surgfirst on survival. This needs to be confirmed in large-scale multicenter studies. We identified clinical and socioeconomic factors that affect treatment selection and survival.

BackgroundThe addition of radiation to chemotherapy in elderly patients with PCNSL remains controversial. Our objective was to assess the trend of combined modality treatment (CMT) and compare its survival with chemotherapy alone and radiation alone in non-HIV patients. MethodsWe identified 6,537 patients who received single treatment modality, combined modality treatment, or no treatment at all between 2004 and 2015 from the National Cancer Database. Factors affecting treatment selection were investigated using a logistic regression model. Annual percentage change (APC) was calculated to assess the trend of CMT use. A propensity score weighting methodology was used to compare survival outcomes. FindingsOnly 12.8% of patients received CMT, and this proportion steadily declined between 2004 (17.7%) and 2015 (8.7%), with APC of -6.0% (95% CI -8.0 to -4.0, p-value Conclusion Socioeconomic factors affect the selection of treatment in elderly patients with PCNSL that can alter outcomes. CMT is falling out of favor in this patient population due to the risks of neurotoxicity. Further work should focus on developing strategies that minimize toxicity and access disparities without compromising survival

Mantle cell lymphoma is an aggressive and incurable subtype of non‐Hodgkin B cell lymphoma. Patients typically present with advanced disease, and most patients succumb within a decade of diagnosis. There is a clear and urgent need for novel therapeutic approaches that will affect mantle cell lymphoma through a unique mechanism compared to current therapies. This study examined the use of RNA interference (RNAi) therapy to attack mantle cell lymphoma at the mRNA level, silencing genes associated with cancer cell proliferation. We identified a lipid nanoparticle formulated with the lipidoid 306O13 that delivered siRNA to JeKo‐1 and MAVER‐1 mantle cell lymphoma cell lines. Three therapeutic gene targets were examined for their effect on lymphoma growth. These included Cyclin D1, which is a cell cycle regulator, as well as Bcl‐2 and Mcl‐1, which prevent apoptosis. Gene knockdown with siRNA doses as low at 10 nM increased lymphoma cell apoptosis without carrier‐mediated toxicity. Silencing of Cyclin D1 induced apoptosis despite a twofold “compensation” upregulation of Cyclin D2. Upon simultaneous silencing of all three genes, nearly 75% of JeKo‐1 cells were apoptosing 3 days post‐transfection. Furthermore, cells proliferated at only 15% of their pretreatment rate. These data suggest that lipid nanoparticles‐formulated, multiplexed siRNA “cocktails” may serve as a beneficial addition to the treatment regimens for mantle cell lymphoma and other aggressive cancers.

Background Bruton tyrosine kinase (BTK) inhibitors (ie, ibrutinib, acalabrutinib) are approved for treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), and can mediate durable responses in some patients; however, relapses are common, primarily due to acquired mutations in BTK enzyme and/or phospholipase C gamma 2 (Albitar F, et al. J Cancer. 2015;6[5]:409-411. Maddocks KJ, et al. JAMA Oncol. 2015;1[1]:80-87. Woyach JA. Clin Adv Hematol Oncol. 2016;14[5]:330-333. Woyach JA, et al. N Engl J Med. 2014;370[24]:2286-2294.). Preclinical studies demonstrated successful generation and robust cytotoxicity of an autologous, non-genetically modified, polyclonal T-cell product (IOV-2001) from BTK-inhibitor-treated patients with CLL (Karyampudi L, et al. HemaSphere. 2019; 3[suppl 1; abstract PF447]), consisting of billions of peripheral blood lymphocytes (PBLs). Compared with pre-ibrutinib and treatment-naïve PBLs, those derived from post-ibrutinib blood samples demonstrated higher-fold expansion from peripheral blood and produced higher levels of IFNγ in response to non-specific T-cell receptor stimulation. Methods IOV-CLL-01 (NCT04155710) is an ongoing, first-in-patient, Phase 1/2, open-label, multi-cohort, dose-finding study designed to evaluate the safety and efficacy of IOV-2001 in patients with CLL/SLL who are progressing or have progressed on ibrutinib or acalabrutinib treatment. PBLs are generated by T-cell expansion from 50 mL of the patient's blood in a 9-day manufacturing process at a centralized GMP facility. The PBL product is then cryopreserved and sent back to the treatment center for infusion into the patient. Treatment consists of a preparative regimen of lymphodepleting chemotherapy (cyclophosphamide IV 500 mg/m 2 and fludarabine IV 30 mg/m 2) for 3 days, followed by 2 days of rest, a single infusion of IOV-2001, and 6 doses of either low-dose (9 MIU SC) or high-dose (600,000 IU/kg IV) interleukin-2 (IL-2; Figure 1). Approximately 1 to 5 clinical sites in North America will treat ~39 to 70 patients across 4 cohorts in 2 phases (Table 1). The primary endpoint for Phase 1 (Cohorts 1a and 1b) is to determine the recommended Phase 2 dose (RP2D) of IOV-2001 followed by IL-2, and for Phase 2 (Cohorts 2 and 3) is to evaluate efficacy of the RP2D of IOV-2001 followed by IL-2, as measured by objective response rate per investigator assessment. Patients ages ≥18 years, diagnosed with CLL/SLL with radiographically measurable disease, Eastern Cooperative Oncology Group performance status of 0-1, and meeting prior therapy criteria according to Table 2 are eligible for inclusion. Four US sites are currently active and enrolling patients. Figure 1 Figure 1. Disclosures Pinilla Ibarz: Sellas: Other: ), patents/royalties/other intellectual property; AbbVie, Janssen, AstraZeneca, Takeda: Speakers Bureau; AbbVie, Janssen, AstraZeneca, Novartis, TG Therapeutics, Takeda: Consultancy, Other: Advisory; MEI, Sunesis: Research Funding. Lister: Oncology Analytics: Other: Academic Board. Woyach: Gilead Sciences Inc: Other: Data & Safety; AbbVie Inc, ArQule Inc, AstraZeneca Pharmaceuticals LP, Janssen Biotech Inc, Pharmacyclics LLC, an AbbVie Company,: Consultancy; AbbVie Inc, ArQule Inc, Janssen Biotech Inc, AstraZeneca, Beigene: Other: Advisory Committee; AbbVie Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company: Research Funding. Graf Finckenstein: Iovance Biotherapeutics, Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Jagasia: Iovance Biotherapeutics, Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Samakoglu: Iovance Biotherapeutics, Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Yadav: Iovance Biotherapeutics, Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Li: Iovance Biotherapeutics, Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Byrd: Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Newave: Membership on an entity's Board of Directors or advisory committees; Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees.

Introduction Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment paradigm for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and other hematologic malignancies. However, its use is associated with serious adverse effects including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Severe ICANS can present with aphasia, mutism, somnolence, seizures, signs of increased intracranial pressure and rarely cerebral edema. Corticosteroids (CS) and IL-6 inhibitors are first line treatment for CRS and ICANS. Prolonged CS use has been associated with decreased over-all survival in CAR T-cell treated patients. Data on effective treatments for CART T-cell induced neurotoxicity is limited, especially in steroid-refractory ICANS. Blood-brain barrier (BBB) disruption and infiltration of myeloid and immune effector cells into the central nervous system are implicated in the pathogenesis of ICANS. This likely explains the role of intrathecal chemotherapy, which has been described in literature for treatment of steroid-refractory ICANS. Here, we report the outcomes of two patients with refractory DLBCL who developed severe ICANS after receiving axicabtagene ciloleucel (axi cel) and treated with intrathecal (IT) chemotherapy. Case Presentation Our first case is of a 66 year old male with diagnosis of R/R DLBCL, who was treated with R-CHOP, followed by R-GemOx, with no response then received axi cel. Patient developed grade 2 CRS and grade 1 ICANS (National Cancer Institute Common Terminology Criteria for Adverse Effects v4.03) on day +2 post infusion, treated with tocilizumab and dexamethasone with good response initially. While tapering dexamethasone on day +5, he developed grade 3 CRS and grade 3 ICANS. Brain MRI did not show any intracranial abnormality and EEG showed no seizure activity. Lumbar puncture (LP) was done on day +7 and showed opening pressure of 32 cm H2O, and 12 lymphocytes. He was started on IV solumedrol and tocilizumab was resumed. CRS improved while neurotoxicity progressed to grade 4 prompting intubation and mechanical ventilation on day +8. On day +9, patient received intrathecal methotrexate 12 mg and hydrocortisone 50 mg. On day +12, neurotoxicity improved to grade 1 and patient was extubated on day +13. Steroid taper stopped on +17. Despite disease response, patient remained hospitalized at day +45 for deconditioning and vocal cord paralysis related to a lengthy hospital stay and intubation. He was eventually discharged, however passed away on day +49 from complications of prolonged hospitalization. Our second case is of a 69 year old female with a diagnosis of R/R DLBCL with CNS involvement, treated with RCHOP x6 followed by salvage chemotherapy with refractory disease, She then received axi cel. Patient developed grade 1 CRS on day +4, treated with tocilizumab and dexamethasone, and patient responded well. On day +9, she developed grade 2 CRS and grade 3 ICANS. At that time, dexamethasone was switched to pulse dose solumedrol and tocilizumab was continued. CT head showed no acute intracranial abnormality and EEG did not show any epileptiform activity. LP showed opening pressure of 21, and 84 lymphocytes. On day +11, patient's CRS resolved, however ICANS developed to grade 4 and patient received 12 mg intrathecal methotrexate and hydrocortisone 50 mg for steroid-refractory ICANS. The very next day, patient showed significant neurological improvement. Steroid taper was initiated and patient's ICANS resolved on day +16. MRI brain showed decrease in size of nodular enhancement along periventricular white matter and left occipital area corresponding to treatment response. She was discharged on day +28 and continues to do well one year out of axi cel infusion Conclusion Our abstract adds to the sparse literature about the use IT chemotherapy in cases with severe ICANS. It also highlights its importance as an alternative potential therapy to high doses and prolonged courses of corticosteroids which is associated with increased morbidity and mortality. Steroid-refractory ICANS has limited treatment options and further evaluation of the use of IT chemotherapy in large scale studies is warranted. Disclosures Kahn: Abbvie: Research Funding, Speakers Bureau; Astrazeneca: Research Funding, Speakers Bureau; Beigene: Research Funding, Speakers Bureau; Epizyme: Research Funding, Speakers Bureau; Genetech: Research Funding, Speakers Bureau; GSK: Speakers Bureau; Karyopharm: Speakers Bureau; Kite: Speakers Bureau; Morphosys: Speakers Bureau; Sanofi: Speakers Bureau; SeaGen: Speakers Bureau. Fazal: Agios: Consultancy, Honoraria, Speakers Bureau; AMGEN: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Speakers Bureau; Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; Glaxo Smith Kline: Consultancy, Honoraria, Speakers Bureau; Incyte: Consultancy, Honoraria, Speakers Bureau; Janssen Oncology: Consultancy, Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Karyopharm Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Sanofi Genzyme: Consultancy, Honoraria, Speakers Bureau; Stemline Therapeutics: Consultancy, Honoraria, Speakers Bureau; Taiho Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Honoraria, Speakers Bureau. Lister: Oncology Analytics: Other: Academic Board.

Introduction Primary CNS lymphoma (PCNSL) is an aggressive form of lymphoid malignancy that occurs exclusively in the brain, meninges, spinal cord, and eyes. The incidence of PCNSL has been increasing, particularly in the elderly population, with a median age at diagnosis of 66 years (Olson J.E. et al., Cancer 2002). The primary modality of treatment for this deadly disease is systemic chemotherapy that includes high-dose methotrexate (HD-MTX), with or without whole-brain radiation. Due to the toxicity of HD-MTX, physicians tend to avoid using it in the elderly population. This was confirmed in previous reports from the 1990s (Panageas K.S. et al., Cancer 2007). In this comprehensive population-based analysis, we sought to examine the patterns of treatment and survival in elderly patients in the 2000s and sought to investigate clinical and socioeconomic predictors of treatment selection. Methods We conducted a retrospective cohort analysis using de-identified data accessed from the national cancer database (NCDB). The NCDB provided records of 2985 patients diagnosed with PCNSL between 2004 and 2015. We excluded patients who are younger than 65 years old, those who tested positive for HIV, and those who started treatment >120 days since diagnosis to account for immortal time bias. Patients were divided into four groups based on treatment received: combined modality treatment (CMT), chemotherapy alone, radiation alone, and no treatment. Exploratory analysis of the patient groups was performed. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Multivariate regression models were used to analyze predictors of the selection of any treatment versus no treatment and for selecting chemotherapy versus no chemotherapy. To account for variable baseline characteristics, we used propensity score weighting methodology to calculate estimates of interest. Survival estimates were performed using the Kaplan-Meier method, and survival differences were tested using the wilcoxon-rank test. Results We identified 1096 patients with PCNSL who fulfilled the inclusion criteria. The median age was 73 (IQR: 68-79). There were 52% males. The majority of the patients were whites (92%), lived in a metropolitan area (78%), treated at an academic/research center (57%). The most common treatment modality used was chemotherapy alone (48%), followed by CMT (22%), no treatment (16%), and radiation alone (13%). On multivariate analysis, age (OR: 0.94, 95% CI 0.92-0.96) and comorbidity score (OR: 0.63, 95% CI 0.52-0.76) significantly predicted receiving any type of treatment. Both age (OR: 0.91, 95% CI 0.89-0.94) and distance (OR: 1.006, 95% CI 1.001-1.01) were predictors of receiving chemotherapy. Median follow up was 12 months (IQR: 3-44). Median OS in months for the four groups was: 43.1 for CMT, 19.4 for chemotherapy alone, 17.2 for radiation alone, and 2.3 for no treatment. (wilcoxon-rank test p-value: 75 year old had lower median OS in general, but receiving CMT had a survival advantage as well. (Figures 1 and 2) Conclusions The majority of PCNSL patients in our analysis received treatment. Our results showed an increased trend of chemotherapy use in elderly patients compared with earlier reports, where radiation alone was the most common treatment modality. The median OS of patients was longer compared with the 1990s data (17 vs. 7 months). CMT was associated with better OS compared with no treatment and chemotherapy alone. Although this was numerically better compared with radiation alone, it was not statistically significant. Younger patients and patients with lower comorbidity scores were more likely to receive treatment. Younger patients and patients who live further from the treating facility were more likely to receive chemotherapy. Longer distance may have led to less radiation use due to the need for complex planning and frequent visits associated with radiation therapy. Our study is limited by its retrospective nature, which makes it at risk of selection bias. Using propensity score weighting methodology strengthens our results. Also, the NCDB lacks certain pertinent variables, such as details of chemotherapy regimens, and toxicity information especially for radiation in the CMT arm which will have practical implications. Disclosures Fazal: Glaxosmith Kline: Consultancy, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Karyopham: Speakers Bureau; Celgene: Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jansen: Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau. Kahn:Genetech: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria; Seattle Genetics: Honoraria; Abbvie: Honoraria; Celgene: Honoraria; AstraZeneca: Honoraria; Beigene: Honoraria.

Introduction The ability of the neoplastic cells to escape from immune surveillance has been considered as a hallmark of cancer. The upregulation of programmed death-1 (PD-1) and programmed death ligand-1/2 (PDL-1) axis is a major immune escape pathway in multiple malignancies including classical hodgkin lymphoma (cHL). Disruption of PD1-PDL1/2 pathway using checkpoint inhibitors (CPIs) leads to reactivation of immune cells to attack malignant cells. CPIs have been studied in cHL in different settings. Here in, we did a systematic review and meta-analysis of phase II and III clinical trials that looked at the efficacy of CPIs in cHL Methods We did a comprehensive literature search, using 4 major databases (pubmed, embase, chocrane, and clinialtrials.gov). We used MeSH terms and related keywords that included all CPIs in generic and trade names, and cHL. We included phase II and III prospective clinical trials in patients > 18 year-old. We excluded case reports, case series, review articles, retrospective and observational studies, and phase I clinical trials. Initial search resulted in 1647 articles. After applying the inclusion and exclusion criteria, we had 13 articles that we explored in details. We stratified the articles according to CPIs and did a pooled-analysis of the complete response (CR) rate. Medcalc was used to do the statistical analysis. Results Of those 13 clinical trials, we had 12 phase II trials and 1 phase III trial. Nivolumab was studied in 7 trials (n=568), pembrolizumab in 5 trials (n=427), and camrelizumab in 1 trial (n=86). Table 1 shows the characteristics of these trials. (table 1) Four studies evaluated the efficacy of nivolumab in the relapsed/refractory (RR) setting. Armand et al (2018) evaluated the efficacy of nivolumab after autologous hematopoietic stem cell transplantation (auto-HSCT), the cohort in this study was divided into 3 groups: patients who received brentuximab vedotin (BV) after auto-HSCT, patients who are BV naïve, and patients who received BV before and/or after auto-HSCT. Overall response rate (ORR) and CR were 68% and 13%, 65% and 29%, 73% and 12%, respectively. Maruyama et al (2017) reported ORR and CR of 81.3% and 25%, in 16 Japanese patients received nivolumab in combination with BV. The ORR and CR in the remaining 2 trials were: 82% and 59%, and 85% and 67%. In the frontline setting, nivolumab showed ORR and CR of 84% and 67% (Ramchandren et al, 2019), 96%-100% and 53-85% (Brockelmann et al, 2019 in 2 different dosing regimens), and 100% and 72% (Yasenchack et al, 2019). Pooled analysis of all nivolumab trials showed CR rate of 47.4 % (95% CI 29.0-66.1) (figure 1) Pembrolizumab was evaluated in 4 clinical trials in the RR setting. Armand et el (2019) reported CR rate of 83% in 25 patients. Chen et al (2019) reported ORR and CR of 76.8 % and 26.1% in patients who relapsed after auto-HSCT and BV, 66.7% and 25.9% in patients ineligible for HSCT, and 73.3% and 31.7% in patients who relapsed after auto-HSCT with no prior exposure to BV. In combination with gemcitabine, vinorelbone , and doxorubicin, pembrolizumab showed ORR and CR of 100% and 93%, respectively. The only phase III clinical trial compared pembrolizumab vs BV in the RR setting showed ORR of 65.6% vs 54% and CR of 24.5% vs 24%, respectively. Only one study evaluated pembrolizumab in the frontline setting, ORR and CR of 100% in 30 patients received 3 cycles of pembolizumab followed by 4-6 cycles of doxorubicin, vinblastine, and dacarbazine. Pooled analysis of all pembrolizumab trials showed CR rate of 54.4% (95% CI 32.6-77.2) (figure 2) Only one trial evaluated the role of camrelizumab as monotherapy or in combination with decitabine. The combination regimen showed ORR and CR of 95% and 71% in CPIs naïve patients, and 52% and 28% in patients previously received CPIs. Camrelizumab monotherapy showed ORR and CR of 90% and 32% in CPIs naïve patients. Conclusion CPIs in cHL have showed high rates of response in the frontline and RR settings, with fairly acceptable toxicity profile. Their efficacy was studied post HSCT and BV, in BV naïve patients, and in HSCT-ineligible patients. Pembrolizumab and nivolumab were the 2 most studied CPIs. Future direction should focus on more studies in the frontline setting, the role of combined CPIs with other CPIs or with novel agents, to spare this relatively young population the long term toxicity of chemotherapy. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.Fazal:Jansen:Speakers Bureau;Jazz Pharma:Consultancy, Speakers Bureau;Stemline:Consultancy, Speakers Bureau;Glaxosmith Kline:Consultancy, Speakers Bureau;Gilead/Kite:Consultancy, Speakers Bureau;Amgen:Consultancy, Speakers Bureau;Novartis:Consultancy, Speakers Bureau;Agios:Consultancy, Speakers Bureau;BMS:Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau;Celgene:Speakers Bureau;Karyopham:Speakers Bureau;Incyte Corporation:Consultancy, Honoraria, Speakers Bureau;Takeda:Consultancy, Speakers Bureau.

Introduction Gray-zone lymphoma (GZL) is a rare lymphoid neoplasm initially described in 2005. The world health organization first recognized it as a separate entity in 2008. These tumors have intermediate morphologic and phenotypic features between diffuse large B-cell lymphoma and Hodgkin lymphoma. There is no treatment guidelines given the rarity of the disease, and being relatively a new entity. In this first population-based analysis of GZL, we focus on combined modality treatment (CMT; chemotherapy and radiation) versus chemotherapy alone as a primary treatment strategy. We sought to examine the effect of each modality on survival and investigate clinical and socioeconomic predictors of treatment selection and survival using the national cancer database (NCDB). Methods We conducted a retrospective cohort analysis using de-identified data accessed from the NCDB. The NCDB provided records of 2176 patients diagnosed with GZL between 2004 and 2016. We excluded patients without histologic or cytologic confirmation of the diagnosis or patient with unrecorded stage information. We also excluded patients who started treatment after 4 months of diagnosis to account for immortal time bias. Treatment was categorized as CMT or chemotherapy alone. Exploratory analysis of the patient groups was performed. Summary statistics are presented as percentages for categorical data and median with interquartile range for quantitative data. Multivariate regression models were used to analyze the predictors of treatment selection and survival. We used propensity score matching methodology for the comparative survival analysis. Survival estimates were performed using the Kaplan-Meier method and survival differences were assessed using the log-rank test. Results We identified 1047 patients with GZL who were treated with CMT or chemotherapy alone between 2004 and 2016. The median age was 63 (IQR 47-74), there were 56.7% Males. The majority of the patients were non-Hispanic whites (80.7%), had insurance (96.1%), had comorbidity score of 0 (75.4%), belonged to a metropolitan areas (83.4%), and were treated at a comprehensive community cancer centers or academic programs (65.5% combined). Only 164 patients (15.7%) received CMT, while 883 (84.3%) received chemotherapy alone. Treatment selection was affected by clinical factors (age and advanced stage) but not socioeconomic factors. Median follow up for the 811 patients with available survival data was 28.8 months (IQR 12.36-50.25). The use of CMT and higher median income were associated with better survival, while increased age, higher comorbidity score, and presence of B symptoms were associated with worse survival. Median overall survival was significantly higher in CMT group compared with chemotherapy alone group (HR 0.541, 95% CI 0.351-0.833, p-value 0.005). Discussion Number of patients with GZL increased gradually over the years, which reflects increased insight and recognition of this disease entity. The use of CMT is continuously increasing over the years. Receiving CMT had a survival advantage over chemotherapy alone. In contrary to a multicenter retrospective analysis by Evans et al where advanced stage was the only important predictor of survival in GZL, our analysis showed other clinical and socioeconomic factors that affected outcomes. Radiation is associated with increased cost, it requires complex planning, and creates significant psychosocial burden, in addition to toxicity which could have contributed to its less use with older patients. A previous retrospective report showed no effect on survival with use of consolidative radiation in 37 patients. Larger sample size in our cohort could have contributed to a different outcome. Our study is limited by its retrospective nature and lack of certain pertinent variables, such as details of chemotherapy regimens. Being a relatively new entity limited median follow up to 2.4 years. Longer follow up and larger prospective studies are needed to evaluate the role of consolidative radiation in GZL and its toxicity. Our study adds to the sparse literature about GZL and identifies clinical and socioeconomic factors that can affect treatment selection and outcome that should be taken in consideration in future research. Figure 1 Disclosures Fazal: Jazz Pharma: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Jansen: Speakers Bureau; Stemline: Consultancy, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Karyopham: Speakers Bureau; Celgene: Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau. Kahn:AstraZeneca: Honoraria; Celgene: Honoraria; Seattle Genetics: Honoraria; Genetech: Honoraria; Abbvie: Honoraria; Beigene: Honoraria; Takeda: Honoraria; Karyopharm: Honoraria.

Introduction Determining eligibility for autologous hematopoietic stem cell transplantation (Auto-HCT) is considered standard of care for patients with newly diagnosed multiple myeloma (MM). In addition to comorbidity score, age >65 years is still a commonly used criterion to deem patients ineligible for transplant. Here we report the outcomes of patients ³ 65 years with MM who underwent Auto-HCT following risk stratification using HCT-CI along with other eligibility criteria. Methods We performed a retrospective analysis of 102 patients, who underwent Auto-HCT between 1/1/1999 and 12/31/2018 at Allegheny Health Network Cancer Institute. Ninety two patients (90%) received conditioning with Melphalan 200 mg/m2. Median overall survival (OS) was estimated at day+100, day+180, 1, 2, 3 and 5 years post Auto-HCT. Non-relapse mortality (NRM) was assessed at day 100 post Auto-HCT. Results For a cohort of 102 patients, a total of 119 Auto-HCT were performed. Median age at transplantation for the entire cohort was 69.2 years (65.1 - 79.4 years). Thirty five (34.3%) patients were aged ³70 years. Median HCT-CI score was 3 (range: 0-8). Median time to Auto-HCT following diagnosis was 9.1 months (range: 4.7- 176.7 months). Median time to ANC500 and PLT20 was 13 days (range: 10-15) and 18.4 days (range:8-42) respectively. Median OS by Kaplan-Meier analysis for the entire cohort vs patients ³ 70 years at day+100, day+180, 1, 2, 3, and 5 years post Auto-HCT was 97.1%, 95.1%, 91.2%, 83.3%, 78.4%, and 63.7% respectively vs 100%, 100%, 97.1%, 82.9%, 77.1% and 68.6% respectively. Median OS in months for patients Conclusion Auto-HCT in patients with MM aged ³65 years is safe, effective and should be offered to all patients with a reasonably good performance status. A fully integrated approach is required to accomplish the needs of elderly patients including consideration for quality of life.

Background The treatment options in Multiple Myeloma (MM) are variable and may involve combinations of chemotherapy, immunomodulatory therapy, monoclonal antibodies and stem cell transplant. In the present study, we hypothesized that socioeconomic factors impact the treatment and survival of patients with MM who receive systemic therapy as firstline treatment. Methods We queried the National Cancer Database (NCDB) for patients with MM (ICD-0-3 code 9732) diagnosed from 2004-2016. We included only that received systemic therapy as first line treatment. Active MM patients were defined as those treated within 120 days of diagnosis. Enrollment rates were calculated as receipt of primary therapy as the incident-event (numerator) over time-to-initiation of therapy or TTI (denominator) and used to calculate incident-rate ratios that was further analyzed using Poisson regression analysis- reported as enrollment-rate ratios (ER, 1, p-value Citation Format: Thejus Jayakrishnan, Veli Bakalov, Zena Chahine, John Lister, Rodney Wegner, Santhosh Sadashiv. Disparities in the enrollment to systemic therapy and survival for patients with multiple myeloma [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-212.

Background Diffuse Large B-Cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL), accounting for approximately 22% of newly diagnosed non-Hodgkin's lymphoma per year in the United States. Combination chemoimmunotherapy with or without radiation therapy is recommended for the upfront treatment of DLBCL (Yang Liu, AJH,2019). A minority of patients undergo surgery prior to the initiation of systemic therapy for symptom relief or treatment of complications related to the disease. There are concerns on the delay in initiation of systemic therapy when surgery is performed and the potential impact on long term survival in this aggressive chemosensitive disease. We aimed to explore the characteristics of patients undergoing surgery prior to systemic therapy (sxfirst), the predictors for sxfirst and the survival outcomes. Methods We queried the National Cancer Database for patients with DLBCL (ICD-0-3 code 9680) diagnosed from 2006-2015. Inclusion criteria were patients that received systemic therapy as first-line course of treatment and excluded patients with incomplete or missing data for disease stage, treatment characteristics and follow-up. We also excluded patients who underwent biopsy procedures for diagnosis and local procedures such as tumor destruction or ablation. Subgroup analysis of patients that received sxfirst was performed. Time-to-initial therapy (TTI) was defined as time in days (d) from diagnosis to systemic therapy. Survival was measured in terms of months (m) from the day of diagnosis. Stepwise multivariate logistic regression analysis for predictors of sxfirst and propensity score adjusted survival analysis was performed. Results Of 208,748 patients with DLBCL, 138,096 patients met the inclusion criteria of whom 6,381 (4.6%) were sxfirst. The characteristics of sxfirst are summarized in Table 1. Median age was 66 (interquartile range IQR 55-75) years and 61.1% were males. Majority were non-Hispanic whites, had private or medicare insurance, had comorbidity score of 0 and stage I disease. Most patients were treated in comprehensive community cancer centers. The top 5 extra-nodal disease sites were gastrointestinal (26.2%), male reproductive system (16.4%), brain and spinal cord (6.4%), endocrine system (4.1%) and head and neck (3.0%). The median follow up was 47.6 (IQR 14.0-78.9) months. The predictors for sxfirst are described in Table 2. The following disease sites were associated with higher likelihood of sxfirst: male reproductive system (p-value=3 (p-value 0.007), more recent year of diagnosis, advanced stages of disease and presence of B-symptoms. The TTI for systemic therapy was delayed in sxfirst group - 34 (IQR 22-51) days vs. 21 (IQR 11-35) days, p-value Conclusion The findings of the present study are twofold. First, the present study describes the characteristics and predictors of sxfirst among DLBCL patients. Second, if surgery is absolutely necessary prior to systemically treating DLBCL, the study suggests that the delay does not seem to impact long term survival of these patients and is similar to the 5-year overall survival (64%) reported for DLBCL when all stages and treatment strategies are combined (seer.cancer.gov/statfacts/dlbcl). While there are unmeasured confounding factors as a result of the absence of adequate prognostic markers and treatment characteristics in the database, it is possible that surgery truly doesn't impact the survival outcomes significantly. Further evaluation of this practical question is warranted in large scale prospective studies. Disclosures Khan: Abbvie: Honoraria; Genentech: Honoraria; AstraZeneca: Honoraria; Takeda: Honoraria; Celgene: Honoraria; Karyopharm: Honoraria; Beigene: Honoraria; Seattle Genetics: Honoraria. Fazal:Stemline: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau; Jansen: Speakers Bureau; Karyopham: Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Our group has demonstrated that combinations of epigenetic modifiers produce potent synergy in pre-clinical models of PTCL, and has confirmed this data in early phase clinical studies. We showed that the combination of romidepsin and hypomethylating agents, decitabine or azacytidine, uniquely induces the expression of genes, including cancer testis antigens, gamma interferon and endogenous retrovirus. We are conducting a phase 1 study of pembrolizumab combined with pralatrexate alone (Arm A), with pralatrexate + decitabine (Arm B), or decitabine alone (Arm C) in patients with peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma. In addition, we are conducting a Phase 1/2A study of durvalumab combined with oral 5-azacitidine + romidepsin (Arm A), pralatrexate + romidepsin (Arm B), romidepsin (Arm C), or oral 5-azacitidine (Arm D) in patients with PTCL. Patient characteristics are listed in Table 1. We have treated a total of 12 patients across the 2 trials and 4 different Arms including pralatrexate plus pembrolizumab (3 patients), pralatrexate, decitabine and pembrolizumab (3 patients), decitabine and pembrolizumab (3 patients) and azacytidine, romidepsin and durvalumab (3 patients). Twelve patients out of 12 received at least one dose of drug and were evaluable for toxicity. There was a dose limiting toxicity (DLT) for each arm including prolonged grade 3 thrombocytopenia, febrile neutropenia, grade 3 hyponatremia and rash, and cytokine release syndrome, respectively. There were no treatment-related deaths. Eight patients out of 12 are evaluable for response at the time of this analysis. Three out of 8 patients achieved a complete remission, 3 out of 8 patients had a partial remission, and 2 out of 8 patients experienced progression of disease. Interestingly, all of the responses were seen in the triple combination of pralatrexate, decitabine, pembrolizumab and azacytidine, romidepsin and durvalumab. These preliminary clinical data suggest that the addition of immune-checkpoint inhibitors on an epigenetic backbone is safe and demonstrates encouraging responses in patient with PTCL and CTCL. These trials are registered at www.clinicaltrials.gov (NCT03240211, NCT03161223). Patient characteristics (n=12)Median age (range)68 (26-77)Sex, n (%) Male Female6 (50) 6 (50)Race, n (%)White/Non-Hispanic White/Hispanic Black Asian Unknown5 (42) 1 (8) 3 (25) 1 (8) 2 (17)Histology, n (%) PTCL, NOS AITL Mycosis Fungoides PTCL, NOS TFH ATLL Sezary Syndrome ALCL, ALK+2 (17) 2 (17) 2 (17) 1 (8) 1 (8) 1 (8) 1 (8)Stage at diagnosis IB II III IV Unknown1 (8) 2 (17) 3 (25) 4 (33) 2 (17)Median number of prior therapies (range) **2 unknown3 (0-5) Citation Format: Enrica Marchi, Helen Ma, Francesca Montanari, Ahmed Sawas, Jennifer K. Lue, Changchun Deng, Kareema T. Whitfield, Sandra Klein, Matthew V. Matthew, Freedy J. Loffredo, Luigi Scotto, Hyejung Lee, Hye A. Kim, Alice T. Jacobs, Aishling M. Rada, Karen A. Khan, Salvia Salvia, John Lister, Nora N. Benanni, Mark A. Francescone, Pier Luigi Zinzani, Wonseog Kim, Owen A. O'Connor. The integration of PD1 blockade with epigenetic therapy is highly active and safe in heavily treated patients with T-cell lymphoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT160.

Introduction High-dose cytarabine (HD-AraC) is an important component of intensive post-remission therapy for acute myeloid leukemia (AML). Its efficacy in core-binding factor (CBF) AML has been well established but it remains controversial whether HD-AraC is effective before allogeneic hematopoietic stem cell transplantation (Allo-HSCT). Herein, we report our experience at Allegheny Health Network (AHN) regarding the number of cycles of HD-AraC used before Allo-HSCT and its effect on survival. Methods We retrospectively analyzed 49 patients with AML who received HD-AraC after achieving complete remission and underwent Allo-HSCT at our institution between January 2010 and June 2018. Patients with acute promyelocytic leukemia (APL), CBF-AML, and primary induction failure were excluded. The HD-AraC dosing regimen used at our institution is 3,000 mg/m2 IV every 12 hours on days 1, 3, 5 for a total of 6 doses per 28-day cycle. Fifteen patients received 1 cycle, twenty patients received 2 cycles, and fourteen patients received >2 cycles of HD-AraC. The majority of the patients (n=32, 65%) received a myeloablative conditioning (MAC) regimen. The unadjusted probabilities of overall survival (OS) were estimated using Kaplan-Meier method and a multivariate analysis was performed using multiple logistic regression model for odds ratio, 95% confidence interval, and p-value. Number of HD-AraC cycles, age, conditioning regimen, and AML risk stratification per European Leukemia Net (ELN) were used as covariates. Results Median age was 56 years (IQR: 45.1-63.3) and median days to Allo-HSCT was 155 (IQR: 127-202). Our patients received a median of 2 cycles (IQR: 1-3) of HD-AraC before Allo-HSCT. With median follow up of 10 months, the median overall survival for patients who received 1, 2, and >2 cycles of HD-AraC was 9.9, not reached, and 33 months, respectively. Patients who received 2 cycles of HD-AraC showed a trend toward lower mortality with odds ratio of 0.22 (95% CI: 0.03-1.79, p-value 0.158). Conclusion Our data shows that patients who received two cycles of HD-AraC had a lower mortality rate with a trend towards significance. However, the majority of these patients also received a MAC regimen (n=18, 90%) which is significantly (p-value 0.005) more than patients who received 1 cycle (MAC n=6, 40%) and >2 cycles (MAC n=8, 57.1%) of HD-AraC. In addition to this bias that is related to the retrospective nature of the study, the small sample size as well as this being a single center experience limits definitive conclusions. Larger studies are needed to determine the optimal number of HD-AraC as a bridge to Allo-HSCT.

Introduction BK virus hemorrhagic cystitis is a well-recognized complication in patients undergoing allogeneic HSCT and is associated with significant morbidity. PTCY has been used for GVHD prophylaxis in patients undergoing haploidentical or mismatched unrelated donor HSCT. We hypothesized that PTCY is associated with increased incidence of HC associated with BK virus. Objectives • To identify the risk factors for developing BKHC in allogeneic HSCT • To assess the effect of PTCY in development of BKHC in patients with myeloablative (MA) regimen containing total body irradiation (TBI) • To evaluate the risk of concurrent CMV infection and BKHC in allogeneic HSCT with MA conditioning regimen Methods We identified 116 consecutive patients who underwent allogeneic HSCT at our institution between January 2015 and July 2018. The MA regimen (n=42) consisted of fludarabine 50 mg/m2/day IV for 5 days and busulfan 3.2 mg/kg/day IV for 4 days with or without TBI of 200 cGy/day for 2 days (FBT or FB4). The reduced intensity conditioning (RIC) regimen (n=74) consisted of fludarabine 30 mg/m2/day IV for 5 days and busulfan 3.2 mg/kg/day IV for 2 days (FB2). In terms of GVHD prophylaxis all recipients except those undergoing haploidentical and mismatched unrelated transplant received Thymoglobulin 2 mg/kg/daily IV days -2, -1 and 0 (n=80). Recipients of haplo- related and mismatched unrelated donor transplantation received cyclophosphamide 50 mg/kg IV on day +3 and +4 along with Mesna (n=36). All patients received post-transplant immunosuppression with Tacrolimus and Mycophenolate Mofetil. Patients with urinary symptoms were tested for BKV in urine by PCR. Results The median age of patients was 56 years (range 20–76). A total of 31% of patients (n=13) received PTCY in FBT group which was similar to 31% of patients (n=23) in FB4-FB2 (p=0.98). Overall 21.5% patients were diagnosed with BKHC. The patients who received ATG, the incidence of BKHC was 27.5% in FBT group and 11.7 % in FB4-FB2 (p=0.073). The patients who received PTCY, the incidence of BKHC was significantly increased to 69.2% in FBT vs 9% in FB4-FB2 (p=0.0001). The risk of developing concurrent CMV viremia and BKHC was increased to 10.3% in FBT compared to 5.8% in FB2-FB4 (p=0.662). The patients who received PTCY following FBT, the incidence of concurrent CMV viremia and BKHC was increased to 23.1%. as compared to 0% with FB2-FB4. Conclusion Our result shows the addition of PTCY to TBI containing regimen significantly increased the incidence of BKHC. We did not observe increase in the incidence of BKHC in patients receiving PTCY with FB2 or FB4 regimens. Our study revealed an increased incidence of concurrent BKHC and CMV viremia in patients receiving PTCY with FBT which could be due to increased immunosuppression. Our findings suggest that using PTCY as GVHD prophylaxis in patients undergoing MA conditioning regimen including TBI is a risk factor for BKHC.

Extramedullary relapse (EMR) of acute promyelocytic leukemia (APL) is a rare entity, with predilection to involve the central nervous system (CNS). Risk factors include leukocytosis of > 10 × 10 9 /L, bcr3 isoform, microgranular variant, age > 45 years and development of subarachnoid hemorrhage (SAH) during induction therapy. We report a case of APL who completed induction and consolidation therapy but subsequently relapsed with leptomeningeal involvement. Retrospectively, we identified several risk factors for EMR in our patient. Interestingly, the use of all-trans retinoic acid has recently been associated with higher risk of EMR possibly due to up-regulation of adhesion molecules on the surface of the leukemic cell, resulting in their passage through the endothelium to extramedullary tissues. However, data remain conflicting in that regard. Although universal CNS prophylaxis has been suggested, the low incidence of EMR among APL patients renders this strategy less attractive. Nonetheless, active surveillance and CNS prophylaxis may be considered in patients at high risk for EMR, particularly in those of SAH during induction therapy. Further research is needed to evaluate the effectiveness and safety of this strategy. World J Oncol. 2014;5(2):77-80 doi: http://dx.doi.o rg/10.14740/wjon761 w

Summary The multicentre, open-label, two-stage, single-arm, phase 2, PILLAR (PIvotaL Lymphoma triAls of RAD001)-1 study (NCT00702052) assessed the efficacy and safety of everolimus 10 mg/d in adults with confirmed mantle cell lymphoma (MCL) refractory to or intolerant of bortezomib who received ≥1 other antineoplastic agent, either separately or in combination with bortezomib. Primary endpoint was overall response rate (ORR) per investigator review according to the response criteria for malignant lymphoma. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. Fifty-eight patients were enrolled from August 2008–January 2011. Five partial responses were observed (ORR 8·6%; 90% confidence interval [CI] 3·5–17·3%); the study did not meet the prespecified objective of ≥8 objective responses among 57 patients. Median PFS and OS were 4·4 months (95% CI 3·5–6·1) and 16·9 months (95% CI 14·4–29·9), respectively. Grade 3/4 non-haematological toxicities occurred in 70·7% of patients. Based on laboratory values, grade 3/4 thrombocytopenia, neutropenia and anaemia occurred in 13·8%, 13·8% and 8·6% of patients, respectively. Everolimus demonstrated modest activity and acceptable tolerability in heavily pretreated patients with MCL refractory to or intolerant of bortezomib. Future studies evaluating everolimus in a less refractory population or in combination with other targeted therapies in refractory MCL are warranted.

Background: ASTX660 is an oral, novel nonpeptidomimetic, small-molecule antagonist of cellular/X-linked inhibitors of apoptosis proteins (cIAP1/2 and XIAP). ASTX660 is currently being evaluated in a first-in-human phase 1–2 study in patients (pts) with advanced solid tumors or lymphoma (ClinicalTrials.gov NCT02503423). In the ongoing phase 2, ASTX660 has demonstrated preliminary evidence of clinical activity in the relapsed/refractory peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL) cohorts (Mehta et al, presented at the EHA Conference 2019, abs PS1073). Here, we report overall efficacy and safety data from the solid tumors (head and neck squamous cell carcinoma [HNSCC]; cervical carcinoma and other solid tumors) and lymphoma (diffuse large B-cell lymphoma [DLBCL], PTCL, CTCL,) phase 2 cohorts. Methods: Pts received treatment with ASTX660 orally at the RP2D 180mg/day on days 1 to 7, and 15 to 22 in a 28-day cycle. In the first stage 14 evaluable pts were enrolled in each of the 6 phase 2 cohorts with the option to expand the cohort if activity was observed. The primary endpoint was response rate as assessed by the investigator according to the Lugano criteria (DLBCL and PTCL), Global Assessment (CTCL), or RECIST 1.1 (solid tumors). Adverse events (AEs) were assessed per CTCAE V4.03. Results: As of June 4, 2019, a total of 107 pts have received ASTX660 in the solid tumors and lymphoma phase 2 cohorts (HNSCC n=14; DLBCL n=16; PTCL n=26; CTCL n=23; cervical carcinoma n=14; other solid tumors n= 14). Median age (range) was 61 (23-84) years and median number (range) of prior anticancer regimens was 3 (0-12). Among all pts, the most common related AEs of any grade (≥ 10%) were rash (35%), lipase elevation (34%), amylase elevation (29%), diarrhea (14%), fatigue (14%), AST elevation (13%), nausea (13%), and anemia (11%). Related AEs ≥ Grade 3 occurring in ≥ 5% of pts were rash (18%), lipase elevation (16%) and amylase elevation (9%). As of 4 June 2019, 86 pts (80%) discontinued study treatment: 64 (60%) due to progressive disease, 13 (12%) due to AE, 4 (4%) due to death, 4 (4%) due to withdrawal by participant and 1 (1%) for investigator’s decision. At the time of analysis, the ORR was 36% in the PTCL cohort and 15% in the CTCL cohort. One PR was reported in a pt with metastatic melanoma after 12 cycles of treatment. No objective responses were reported in the HNSCC, DLBCL or cervical cohorts. Accrual in the PTCL and CTCL continues; updated efficacy and safety data will be presented at the meeting. Conclusion: In the phase 2 part of the study ASTX660 monotherapy has demonstrated a manageable safety profile and encouraging activity in PTCL and CTCL warranting cohort expansion. Future plans include evaluation of ASXT660 both as mono- or combination therapy in selected malignancies. Citation Format: Antoine Hollebecque, Sarit Assouline, Felipe Samaniego, Benoit You, Francine Foss, Anca Prica, Sarah W. Gordon, Marc Webster, Martin JS. Dyer, Dima El-Sharkawi, Geoffrey I. Shapiro, Lisa Nabell, Sarah P. Blagden, John Lister, Susanna V. Ulahannan, Yijun Sun, Danna Chan, Roberta Ferraldeschi, Monica Mita. Preliminary results of ASTX660, a novel non-peptidomimetic cIAP1/2 and XIAP antagonist, in 107 patients with solid tumors or lymphoma [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr A072. doi:10.1158/1535-7163.TARG-19-A072

Introduction. The diagnosis of multiple myeloma (MM) is often made in elderly individuals (median age at diagnosis 69 years) with over a third of patients exceeding 75 years of age. Many elderly patients are frequently excluded from clinical trials because of predefined upper age limit of 65 years limiting accessibility to autologous stem cell transplant (ASCT) for a large proportion of MM patients. Based on limited multicenter studies and randomized clinical trials in this population, we used the National Cancer Database (NCDB) to assess the outcomes of ASCT in MM patients older than 65 years of age. Methods. We queried the NCDB for patients with MM diagnosed between 2004 -2015 treated with ASCT as frontline therapy, yielding a final cohort of 9,383 patients. Multivariable logistic regression was used to determine the likelihood of receiving ASCT. Overall survival (OS) was calculated from the date of diagnosis to the date of last contact or death using Kaplan Meier methodology. Adjusted hazard ratios (HR) and 95% confidence interval (CI) are reported, with α=0.05 used to indicate statistical significance. Results. The median age was 67.0 (range: 19-90). The majority of patients were older than 65 (58.5%), male (54.7%), Caucasian (75.6%), had government insurance (88%)and had a Charlson-Deyo Comorbidity score (CDCS) of 0 (75.5%). In addition to older age, insurance status, low annual income higher CDCS were associated with lower chances of receiving ASCT (Table 1). Patients in Urban areas (OR 1.377, CI 95% 1.286-1.475), and patients in Academic/Research Centers (OR 4.379 were CI 95%, 3.852-4.978) were more likely to receive ASCT. In patients younger than 65-years of age rate of ASCT was 7.0% in 2004 and increased to 16.7% in 2015. The annual rate of ASCT in patients older than 65-years of age was 1.1% in 2004 and increased to 4.7% in 2015. The multivariable cox proportional hazards of death in patients receiving ASCT was associated with improved survival (HR 0.492, CI 95% 0.473-0.512). Age (>65 years old HR 1.184, 95% CI 1.053-1.331), insurance status (uninsured HR 1.361, CI 95% 1.302-1.422, Medicaid HR 1.365, 95% CI 1.318-1.414, Medicare HR 1.271, 95% CI 1.244-1.299) and higher comorbidity score were associated with worse survival (Table 2). Median survival in patients younger than 65-years old receiving ASCT was 102.6 month versus 66.6 months in patients not receiving ASCT (HR 0.596, 95% CI 0.568-0.624) (Figure 1). Median survival in patients older than 65 years old and not receiving ASCT was 86.3 months versus 28.4 months in patients not receiving ASCT (HR 0.344, 95% CI 0.0320-0.371). Conclusions. The findings of the present study demonstrate decreased utilization of ASCT in older patients with MM, despite significant survival benefit of such therapy. Other factors associated with decreased likelihood of ASCT are such as insurance status and annual income unfold existing disparities in patients with MM receiving ASCT. Disclosures No relevant conflicts of interest to declare.

Background. Use of Autologous Stem Cell Transplantation (ASCT) continues to increase in elderly patients with multiple myeloma. The main goal of our study was to describe in-hospital complications and outcomes after ASCT in patients younger and older than 65-years old utilizing the Nationwide Inpatient Sample (NIS) database. Methods. Cohort selection. The NIS database for the years 2011 to 2015 was queried for the analysis. We used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) in order to identify patients with MM as a primary diagnosis for the hospitalization, and ASCT as a primary diagnosis of the hospitalization. In order to determine comorbidities in selected population we used Clinical Classifications Software (CCS) in conjunction with ICD-9-CM codes. Statistical Analysis.Complex weights were used throughout all calculations, enabling appropriate national projections. Chi-squared and independent t-tests were used for univariate analysis where appropriate. In our study p-value Results.A total of 3,664 patients with MM receiving ASCT were identified in our cohort. Males represented 57.1% of the population, majority of the patients were white, with private insurance, located at the urban teaching hospitals (Table 1). Main insurance in patients older than 65 years old was Medicare. Main comorbidities during hospitalization were anemia, hypertension, electrolyte abnormalities, acute kidney injury, cardiac dysrhythmias, sepsis and pneumonia (Table 2). Overall in-hospital mortality was low, 0.7%, and was significantly higher in patients older than 65 years old (1.3% vs 0.4%, p-value 0.002), however when adjusted for the baseline characteristics with multivariate logistic regression analysis in-hospital mortality was no longer statistically significant (Table 3). Conclusions. We found that patients older than 65 years with MM receiving ASCT are more susceptible to in-hospital complications. However we found that in-hospital outcomes are not statistically significant when adjusted to baseline characteristics, suggesting that the procedure is safe even in the elderly population. Findings of our study can be used to design future randomized controlled trials. Disclosures No relevant conflicts of interest to declare.

We previously reported the enrichment and sorting of small CD31+ cells from human umbilical cord blood by magnetic bead depletion of lineage+ and CD34+ cells. We also reported different lineage/CD34+ depletion strategies [combining Lineage depletion and CD34+ UltraPure kits vs Diamond CD34+ kit] results in different input populations for sorting; CD31+ cells could be sorted from either. Here we report adding the missing component from the alternate lineage-depletion cocktail [anti-CD61 microbeads to Lineage depletion kit/anti-CD123 microbeads to Diamond kit] results in identical input populations, with the CD31+ target cells comprising >20% of input population, permitting rapid, high-purity sorting. We have performed sorts with Influx [B-D] and Tyto [Miltenyi] sorters, yielding 125,000 to 750,000 cells [92-98% pure] in 15 minutes. We show purified small CD31+ blast-like cells express the ESC marker alkaline phosphatase, as well as CD4, CD90 and CxCR4. We have been able to successfully isolate our CD31+ cell population from frozen cord blood samples stored in DMSO/FBS after red cell depletion. Frozen storage results in decreased MNC recovery, but CD31+ cell yields appear unaffected, further improving the enrichment of the CD31+ cell population. This is similar to what we have seen with frozen samples for CD34+ HSC isolation. The ability to use frozen samples is greatly improved by the using of Miltenyi's Tyto Running Buffer, a cGMP-compliant wash and transport solution which contains Tytonase to prevent cell clumping. Tyto Running Buffer can be used in the magnetic bead depletion steps without affecting overall yields. These findings permit rapid sorting of highly purified CD31+ cells, which can be used for gene expression profiling and cell culture.

Introduction Disease Status of AML patients at the time of HSCT is an important factor in predicting their survival. We hypothesize that MLFS (as per IWG criteria) identifies a group of patients that have better outcome than PIF (as per CIBMTR criteria). Objectives • To identify group of patients previously categorized as PIF by CIBMTR pretransplant that may have favorable outcome with HSCT. • To assess the outcome of patients with primary refractory disease by IWG criteria with HSCT. Methods We retrospectively analyzed 78 patients with AML who underwent allogeneic HSCT between June 2008 and December 2017 at our institution. We assessed the disease status at time of transplant as per CIBMTR criteria as complete remission (CR) defined as 1000, platelets >100,000 with transfusion independence, and primary induction failure (PIF) defined as not achieved CR or CRi. We also assessed the patients at time of transplant as per IWG criteria as CR (similar to CR as per CIBMTR but does not require normal maturation), morphologic leukemic-free state (MLFS) defined as 5%. We compared the OS at one year for the above groups. The patients received myeloablative conditioning with FBT or reduced intensity conditioning with FB2. Results Per IWG criteria, The OS at 1 year was 62 % in the CR group (n=29), 65% in the MLFS group (n=17) and 22% in the PRD group (n= 32). Our analysis revealed an overall statistically significant difference between CR v PRD, p=0.0009 and MLFS v PRD, p=0.0006. When we used the CIBMTR criteria, both MLFS and PRD were reclassified into the PIF group with OS of 34% (n=49). Conclusion Disease status prior to transplant is a predictor of outcome after allogeneic HSCT. Our analysis shows better survival for patients who achieved MLFS prior to transplant according to IWG criteria as compared to patients who were classified as primary induction failure by CIBMTR criteria. We intend to prospectively use the IWG criteria pre-transplant in our patients to help predict their survival at one year.