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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

Human immunodeficiency virus (HIV) infection may be a predictor of undertreatment of patients with lymphoma. We hypothesized treatment with systemic therapy (SysT) or hematopoietic stem cell transplantation (HCT) in the first-line setting leads to improved outcomes and sought to compare the predictors for treatment and outcomes with non-HIV (HIV-) patients.Patients with lymphoma diagnosed between 2004 and 2015 were extracted from the National Cancer Database (NCDB). Patients were categorized as HIV+ and HIV-. First-line treatment was categorized as no systemic therapy reported (noSyst), SysT, or HCT. Multivariate analysis to predict treatment and survival was performed.We identified 552,513 lymphoma patients, of whom 11,160 HIV+ versus 349,607 HIV- patients were eligible for analysis. Among HIV+, the positive predictors for SysT were insurance and higher income, whereas female sex and minority racial status predicted lower likelihood for SysT. Forty HIV+ patients underwent HCT. Treatment of HIV+ lymphoma patients resulted in improved outcomes: 3-year overall survival 43.6% in noSyst versus 58.1% SysT (hazard ratio [HR] 0.56; 95% confidence interval [CI], 0.52-0.61; P .005) versus 62.2% HCT (HR 0.42; 95% CI, 0.14-1.3; P = .08). The outcomes were lower compared to non-HIV patients (3-yr overall survival 67.3% with SysT and 62.2% HCT).Patients with lymphoma with HIV benefit from SysT when feasible but outcomes are worse than non-HIV patients. HCT should be offered to HIV+ patients with lymphoma in the appropriate clinic setting. Individual characteristics of the patients and complications could not be evaluated in the present study but should be a focus for future research.

Introduction Multiple myeloma (MM) is the second most common hematological malignancy, accounting for 1% of all cancers, with median age of diagnosis between 66–70 years. MM remains incurable despite advances in treatment over time. Lenalidomide is an important medication used in induction therapy for MM and is also used for maintenance therapy for standard risk patients. With its increasing use, data is emerging about its use being associated with increased risk of secondary primary malignancies (SPM), especially when used as maintenance therapy. Case series: In this case series, we describe three patients with refractory MM treated with lenalidomide maintenance who later developed sALL. All had a common presentation of pancytopenia. They developed cytopenias while being on lenalidomide which was refractory to lenalidomide cessation, prompting bone marrow biopsy. Management and outcome: Lenalidomide was subsequently stopped, and patients were treated for secondary B-ALL. However, all passed away either due to relapse of disease or complications arising from treatment. Discussion: The mechanism of lenalidomide associated SPMs is not well understood however its incidence is well documented. At least 13 cases of ALL (predominantly B-cell ALL) following Immunomodulator imide drugs (IMiDs) have been reported in literature. An analysis of a larger cohort of patients is required to determine causality of lenalidomide with sALL. However, benefits of maintenance lenalidomide in patients with MM outweighs the risk of developing SPMs. Albeit persistent pancytopenia on lenalidomide therapy should be evaluated with bone marrow biopsy since it could be caused by secondary B -cell ALL.

Introduction Ankylosing spondylitis is an autoimmune disease with chronic inflammation of the spine and sacroiliac joints that is commonly treated with immunosuppressants including disease-modifying antirheumatic drugs and anti-tumor necrosis factor alpha therapy. Case report A 75-year-old female with active ankylosing spondylitis on treatment with etanercept was referred to us for newly diagnosed IgG kappa free light chain multiple myeloma. After failing induction with revlimid, bortezomib, and dexamethasone, she was initiated on carfilzomib. Following the achievement of adequate response to induction, she underwent an autologous hematopoietic stem cell transplant selected for CD34+ cells with melphalan 200mg/m2 conditioning regimen. Given high-risk cytogenetics, i.e. monosomy 17 (17p) and hypodiploidy, she received two cycles of carfilzomib consolidation post-transplant. The patient tolerated the transplant well with successful engraftment and achieved complete remission of multiple myeloma with no detectable M spike, negative immunofixation study, and normalization of light chain ratio. While being off etanercept since the transplant, she noticed complete relief from joint pains related to her ankylosing spondylitis without a need to use the pain-relieving medications. Management and outcome: The patient has sustained remission of ankylosing spondylitis for two years post-transplant without flares or symptoms. She continues to remain off immunosuppressants. Discussion Although our patient had a coincident and unprecedented resolution of ankylosing spondylitis after receiving the hematopoietic stem cell transplant, this case consolidates the idea of transplant as a potential treatment option for ankylosing spondylitis and other rheumatological conditions.

Ibrutinib, a Bruton's tyrosine kinase inhibitor has reformed the treatment of various B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's macroglobulinemia. Although generally well tolerated, here we describe our institutional experience of unique adverse effects encountered with the use of ibrutinib in patients with B-cell lymphomas.This is a retrospective observational study done at a tertiary care facility, to evaluate adverse events in patients with B-cell malignancies on treatment with ibrutinib between 2014 and 2018. Further details including type of malignancy, cytogenetics, interventions for treatment of the side effect, and outcomes were obtained through electronic health record.We found 10 patients with unique adverse events related to ibrutinib. Among those, six had chronic lymphocytic leukemia, two had Waldenstrom's macroglobulinemia, and two had mantle cell lymphoma. The events included palindromic rheumatoid arthritis, diffuse spongiotic dermatitis, bullous pemphigoid, recurrent hemorrhagic stroke, peripheral neuropathy, recurrent paronychia, intramedullary fibrosis, recurrent joint pains, pulmonary aspergillosis, dyspnea with exacerbation of atrial fibrillation, and resolution of autoimmune hemolytic anemia.Our case series illustrates the wide variety of unique events recognized in patients treated with ibrutinib, some of which required cessation and most had dose reduction of the treatment. Thus, stressing the importance of early identification and intervention for the events to avoid worsening of toxicity and inability to continue treatment in such patients.

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 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.

Hospitalized patients with hematological malignancy (HM) suffer an increased incidence of venous thromboembolism (VTE). We sought to identify risk factors and rate of VTE in hospitalized patients with HM using National Inpatient Sample (NIS) for the years 2011 to 2015. We used ICD-9 codes to identify patients with HM as the primary diagnosis and VTE as a secondary diagnosis for hospitalization. The rate of VTE was highest in patients with acute myeloid leukemia (6.6%) followed by acute lymphocytic leukemia (6.1%) and non-Hodgkin's lymphoma (6.0%). The highest risk of VTE occurred among patients with HM receiving chemotherapy (OR 1.68; 95% CI 1.567-1.809) followed by infection such as pneumonia (OR 1.31; 95% CI 1.201-1.436) and sepsis (OR = 1.66; 95% CI = 1.524-1.621). Chemotherapy had the highest risk of developing VTE during hospitalization followed by sepsis and pneumonia. The identification of patients with HM most at risk for VTE could be used to design and test prophylactic strategy.

Background Socioeconomic disparities impact access to treatment and outcomes for patients with cancer. Affordable Care Act (ACA) sought to mitigate some of these disparities In the present study, we examined the influence of socioeconomic factors on patients facing delay in treatment initiation and the impact of Affordable Care Act (ACA). Methods We queried the National Cancer Database (NCDB) for patients with MM (ICD-0-3 code 9732) diagnosed from 2004-2016 who received any therapy. Active MM patients were defined as those treated within 120 days of diagnosis. Time to initiation (TTI) was defined as time in days (d) from diagnosis of cancer to initial myeloma therapy and divided into quartiles. Patients belonging to 4th quartile for TTI constituted the delayed treatment group (delayed-TTI). Study period was divided into pre-ACA and post-ACA using 2010 as cut-off. Multivariate logistic regression analysis was used and p-value 0.05 was used for statistical significance. Results We identified 65,723 patients meeting the eligibility criteria (28,814 pre-ACA and 36,909 post-ACA respectively). Median age was 68 (Interquartile Range IQR 59-76) years, included 55.1% males and majority insured patients (96.4%). Racial distribution was 66%(non hispanic whites-NHW), 20%(non hispanic blacks-NHB), 6%(Hispanics-H). Median TTI were 13 (IQR 5-27) days overall and 42 (33-58) days for delayed-TTI group. NHB and H races were associated with delayed-TTI in the multivariate model - Odds Ratio OR 1.18 (IQR 1.09-1.27)p-value Citation Format: Thejus Jayakrishnan, Veli Bakalov, Natalie Callander, Santhosh Sadashiv, Sikander Ailawadhi. Impact of the Affordable Care Act on timeliness to treatment 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-204.

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.

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.

Treatment of diffuse large B cell lymphoma (DLBCL) remains challenging in elderly population and systematic reviews are lacking in this area. Medline and Cochrane Register of Controlled Trials in addition to conference proceedings were searched for therapeutic clinical trials on frontline treatment of DLBCL in adults ≥60 in post-rituximab era. Forty-one out of 713 reviewed papers met our inclusion criteria. Six cycles of rituximab, cyclophosphamide, vincristine, prednisone (R-CHOP) administered every 21 d remain the standard treatment for fit elderly, with no role for maintenance rituximab. For individuals ≥80, the strongest evidence favors rituximab/ofatumumab-miniCHOP. Numerous alternative approaches including the use of liposomal anthracyclines, dose and regimen adjustment to frailty/comorbidity score, brief duration regimens, and consolidative radioimmunotherapy have produced promising outcomes and could be considered for R-CHOP inappropriate elderly. Phase III randomized trials studying the efficacy of liposomal vincristine, extended-exposure rituximab, and lenalidomide plus R-CHOP are ongoing.

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.

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 Multiple myeloma is a common hematological malignancy. In 2016, there were an estimated 131,392 people living with myeloma in the United States and accounted for 2% of all cancer related deaths. Studies among cancer patients have repeatedly demonstrated that sociodemographic factors impact timeliness of treatment and in turn, survival (Kelly et al. Blood,2016). The treatment options in multiple myeloma are variable and may involve stem cell transplant , chemotherapies and biological therapies. We hypothesized that sociodemographic factors impact the time to initiation of first line chemotherapy in patients with multiple myeloma. We also explored if these factors influenced outcomes. Methods We queried the National Cancer Database for patients with multiple myeloma (ICD-0-3 code 9732) diagnosed from 2004-2016. We excluded patients who were considered for stem cell transplant or other modalites to include only those who received chemotherapy as first line treatment. Active myeloma patients were defined as those who were treated within 3 months (120 days) of diagnosis based on similar methodology in previous studies (Ravindran et al. Blood Cancer J,2016). Time to initiation (TTI) was defined as time in days (d) from diagnosis to initiation of systemic chemotherapy.Survival was measured in terms of months (m) from the day of diagnosis. Stepwise negative binomial regression and Cox proportional hazard models were used for analysis. Results Of 160,900 patients with multiple myeloma, we identified 71,523 patients meeting the eligibility criteria. Median age was 68 (range 21-90) years and 55% were males. Median TTI was 19d (range 0-120d) and median overall survival was 34 months. Even though the TTI increased from 24d (2004) to 27d (2016) this was not significant when other variables were adjusted. The overall median survival improved by 10 months between 2004 and 2012 (28 months to 37 months). Determinants of increased TTI in a multivariate model included African American race (p-value Conclusion The findings of the present study are twofold. First, while not as pronounced as in other cancer cohorts, disparities do exist in timeliness to chemotherapy initiation. The longer TTI in academic centers is interesting but may reflect a more complicated patient population. Second, shorter time to therapy does not necessarily lead to improved outcome, likely reflecting high risk features not captured by standard assessments. This is similar to other studies in hematological malignancies and supports the proposition that clinical trials should accommodate patients who need urgent therapy to detect treatment effects in high‐risk groups (Olszewski et al. Br J Hem,2018). 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.

11589 Background: Opioid medications are the mainstay for treating cancer pain. Goal of this study was to identify risk factors for opioid abuse/dependence in patients hospitalized with cancer, explore whether risk of opioid abuse/dependence varies by cancer type and to assess whether opioid abuse/dependence in cancer patients effects the outcomes of hospitalization. Methods: The Nationwide Inpatient Sample for the years of 2011-2015 was queried for the analysis. We used ICD-9-CM codes of solid tumors as a primary diagnosis for hospitalization, and opioid abuse/dependence as a secondary diagnosis of the hospitalization. We performed univariate and multivariate logistic regression analyses to examine the association between risk factors and opioid abuse/dependence. Data were analyzed using SAS v9.4 (SAS Institute, Cary, NC). Results: Total of 524,624 patients were included in our cohort. Rate of opioid abuse/dependence was highest in patients with liver cancer (1.77%). Opioid abuse/dependence was less associated with age (>65 years old: OR 0.29, 95% CI 0.21-0.39). Patients with Medicaid insurance associated with increased risk of opioid abuse/dependence comparing to other insurances (OR 5.29, 95% CI 4.78-5.86). Strongest association with opioid abuse/dependence were in patients with liver cancer (OR 6.07, 95% CI 5.11-7.20) followed by head and neck cancer (OR 3.20, 95% CI 2.67-3.84). Substance abuse (OR 9.9, 95% CI 9.04-10.84), mental disease (OR-2.87, 95% CI 2.64-3.13) and nutrition deficiency (OR-2.09, 95% CI 1.90-2.31) were highly associated with opioid abuse dependence. Inhospital mortality rate, total cost of hospitalization, and length of stay were significantly higher in patients with opioid abuse/dependence (Table). Conclusions: We identified risk factors for opioid abuse/dependence in hospitalized patients with cancer and demonstrated that risk of opioid abuse varies by cancer type, and opioid abuse/dependence affects the outcomes of hospitalization. Findings of our study can be used for development of the screening tools with higher sensitivity and specificity for predicting the risk of opioid abuse/dependence in cancer patients.[Table: see text]

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.

Introduction and Objectives Multiple myeloma (MM) is a disease of the elderly with the median age of diagnosis being 66 years and rare in the population younger than 50 years. Younger patients generally undergo autologous HCT as part of their treatment once they achieve an adequate response. Overall survival in patients with MM has dramatically improved over the last 2 decades with the advent of novel agents. The purpose of this retrospective analysis was to evaluate the disease behavior and transplant outcomes in patients younger than 50 years. Methods We retrospectively reviewed the charts of 29 patients aged ≤50 who underwent autologous HCT between May 2003 and Dec 2017 at our institution. All patients received Melphalan as their conditioning regimen. 28% (n=8) of the patients had renal insufficiency at the time of diagnosis (serum Creatinine ≥ 2.0 mg/dl). Results 38 auto-HCTs were performed in this group of patients. 7 patients underwent salvage transplant and 2 patients underwent planned tandem auto-HCT. Nearly 80% (n=23) patients had Salmon Durie stage 3 disease at the time of auto-HCT. Overall survival for the entire cohort was 109 months and PFS was 51 months. Median age at diagnosis was 46 years. The median age of the first transplant is 47 years. Median time to relapse/progression was 31 months after auto-HCT for the entire cohort. For patients with high-risk cytogenetics (28%, n=8) median time to relapse was 13 months compared to 72 months in standard risk patients. There was total of 12 deaths in the entire cohort with the majority of deaths (10/12) due to disease progression/relapse and 1 died from a secondary malignancy. Median time to relapse/progression after salvage HCT was 16 months. Of the 7 patients who underwent salvage HCT, 3 died secondary to disease progression with a median time to death is 12.6 months. Conclusion Despite recent advances in the treatment of multiple myeloma, younger patients with high-risk disease status continue to have poor outcomes. Aggressive induction regimens and possible planned tandem Auto-PBSCT may be a reasonable approach to improve outcomes in younger patients with high-risk disease status. Further studies with a larger cohort are warranted to corroborate our findings and also find ways to improve survival in this high-risk group.

Mantle cell lymphoma (MCL) is a B-cell lymphoma that accounts for 3% to 10% of the non-Hodgkin forms of lymphoma. MCL almost universally expresses CD 20, the target of the monoclonal antibody rituximab. Therapy frequently combines rituximab with other chemotherapeutic agents. Administration of rituximab intravenously is well tolerated but frequently causes infusion reactions. Hematologic toxicity is seen less commonly but is well defined. Neutropenia, anemia, and thrombocytopenia have been described and often occur in the 10to 14-day window after rituximab infusion, similar to that seen with conventional chemotherapeutic agents. Isolated cases of acute severe thrombocytopenia after rituximab infusion for treatment of MCL have been reported, but this toxic event is uncommon. We identified 5 cases of acute severe thrombocytopenia occurring within 3 days of the administration of rituximab, suggesting that this toxic event might occur more frequently than previously recognized. Our series shows that acute severe thrombocytopenia is not always associated with infusion reactions, suggesting that the pathogenesis of these two toxic events might be different. Acute severe thrombocytopenia is reported more commonly in MCL than in other lymphomas treated with similar regimens. Four of the 5 patients received platelet transfusion. Subsequently, all the patients exhibited rapid recovery from thrombocytopenia without bleeding complications. Because acute severe thrombocytopenia appears to be transient, unpredictable, and not associated with bleeding complications, we would caution against the cessation or dose reduction of rituximab when treating MCL.

e present the case of an 82-year-old Caucasian female who was evaluated by hematology oncology for further work up and management of her chronic but progressive anemia. She reported weight loss, poor appetite, fatigue, nausea, several episodes of non-bloody diarrhea and increased abdominal girth over the past 3 months. On admission, her hemoglobin was 8.9 gm/dL, platelets were 43 k/mcl, WBC was 5.49 K/mcl with absolute neutrophil count of 3.73 k/mcl and 0% peripheral blasts. Her metabolic panel was abnormal for elevated LDH (245 U/L) and alkaline phosphatase (207 U/L). Her liver function tests were normal except for albumin of 2.5 g/dl. Computed tomography (CT) of the abdomen/pelvis showed splenomegaly, ascites, and retroperitoneal lymphadenopathy, a concern for a lymphoproliferative or metastatic disease. A bone marrow biopsy and aspirate performed to determine the cause of her progressive anemia and thrombocytopenia revealed hypercellularity (90%) and increased blasts (35% on the touch preparation). The blasts had scant cytoplasm and fine chromatin (blue arrows in Figure 1). In addition, there were paratrabecular infiltrates of round to spindled mast cells (red arrow in Figure 1), which by immunohistochemistry were strongly positive for tryptase (shown in Figure 2), CD117, CD68 and CD25. The blasts were weakly positive for CD117 and strongly positive for myeloperoxidase, CD56, Bcl-2, and CD43 (not shown). The aspirate was severely hemodiluted, likely due to the reticulin fibrosis observed in the biopsy. Flow cytometry specimen was also hemodiluted (9% blasts) with the following myeloid immunophenotype: CD33 positive CD13 positive CD56 positive CD117 partially positive CD34 negative HLA-DR negative. Based on these findings the patient was diagnosed with AML and SM, a subset of systemic mastocytosis with associated clonal hematologic non-mast cell lineage disease (SM-AHNMD). The patient’s diarrhea responded briefly to antimotility agent loperamide, but while awaiting definitive treatment plan, her symptoms worsened rapidly and required admission for severe, profuse non-bloody diarrhea, dehydration and abdominal distension. Splenomegaly and ascites were noted on clinical exam. Labs continued to show anemia and thrombocytopenia. Initial test was positive for clostridium difficile (C. diff). This was successfully treated with metronidazole and then with oral vancomycin. Subsequent tests for C. diff, other infectious agents and transglutaminase IgA antibody were negative. However, the patient continued to have multiple episodes of diarrhea with little relief from antimotility agents. Diarrhea was deemed secondary to SM. Extensive work up for portal hypertension was non-diagnostic. She could not undergo colonoscopy and liver biopsy due to thrombocytopenia. As a consideration for treatment with imatinib she was tested for BCR/ABL and PDGFRA fusion genes which were negative. KIT mutation analysis could not be performed due to lack of tissue sample. After a lengthy discussion with the patient regarding various options of treatment, she chose palliative care and hospice. However, severe diarrhea limited her transition to hospice; she was then started on a trial of octreotide every 8 h for her diarrhea. She had a rapid response with dra

Background. Hospital course of patients with hematologic malignancies associated with multiple complications, such as venous thromboembolism (VTE) which significantly affects morbidity and mortality. Compared to the general population patients with hematologic malignancies carry series of risk factors of VTE. Goals of this study were to describe demographic characteristics as well as define the risk factors of VTE in hospitalized patients with hematologic malignancies. Our study was focused on acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), chronic myeloid leukemia (CML), Non-Hodgkin's lymphoma (NHL), Hodgkin's Disease (HD), multiple myeloma (MM). Methods. Cohort selection. The Nationwide Inpatient Sample (NIS) database from the Healthcare Cost and Utilization Project (HCUP) of the Agency for Healthcare Research and Quality (AHRQ) for the years 2011 to 2015 was queried for the analysis. We used International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and corresponding ICD-10-CM codes (for the period of 0ctober 1 - December 31, 2015) in order to identify patients with hematologic malignancies as a primary diagnosis for the hospitalization, and VTE as secondary 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. Percentages in all tables and figures reflect national estimates. Chi-squared and independent t-tests were used for univariate analysis where appropriate. We performed logistic regression analyses to examine the association between risk factor and VTE. In our study p-value Results. A total of 80,078 patients with hematologic malignancies were hospitalized from 2011 to 2015. Males represented 56.1% of the population, majority of the patients were white (69.5%), greater part of the patients were older than 35 years of age (35-65 42.6%, >65 48.8%) (Table 1). Main comorbidities during hospitalization were anemia (58.1%), followed by hypertension (49.1%), fluid disorders (40.1%) and coagulopathies (24.5%) (data not shown). Rate of VTE in all patients was 5.3% and was evenly distributed among genders and races. Rate of VTE was highest in patients with AML (6.6%) followed by ALL (6.1%), and NHL (6.0%), and lowest in patients with MM (3.49%) followed by CLL (3.31%), and CML (3.31%) (Table 2). The highest risk of VTE among patients with hematologic malignancies were in patients receiving chemotherapy (OR=1.684 95% CI=1.567-1.809) followed by infections such as pneumonia (OR 1.313 95% CI 1.201-1.436) and sepsis (OR=1.66 95% CI=1.524-1.621). Other comorbidities such as congestive heart failure, liver disease, coagulation disorders and acute renal failure were associated with significantly higher risk of VTE with OR varying from 1.1 to 1.2. (Table 3) Conclusions. In this retrospective large US inpatient database analysis, we found that average rates of VTE in patients with hematologic malignancies was 5.3% and was highest in patients with AML. Patients receiving chemotherapy had highest risk of developing VTE during hospitalization followed by patients with infections such as sepsis and pneumonia. Higher rates of VTE in patients receiving chemotherapy and patients with sepsis was previously described, however our findings indicate that rate of VTE remain high in these population. Findings of our study can be used for development of the appropriate antithrombotic prophylactic strategies in hospitalized patients with hematologic malignancies. Disclosures No relevant conflicts of interest to declare.

e19010Background: All-trans retinoic acid (ATRA) and arsenic trioxide (ATO) have revolutionized the treatment of acute promyelocytic leukemia (APML). Anthracycline is added at induction for high ri...

Acute myeloid leukemia (AML) patients aged ≥ 60 years tolerate standard induction chemotherapy poorly. Therapy with azacitidine at a dose of 75 mg/m(2)/day for 7 days appears to be better tolerated, and is approved by the Food and Drug Administration (FDA) for the treatment of elderly AML patients with bone marrow (BM) blast counts of 20-30%. Here, we report the results of a prospective, phase 2, open-label study that evaluated the tolerability and efficacy of a 5-day regimen of single-agent subcutaneous azacitidine 100 mg/m(2)/day administered every 28 days in 15 elderly patients with newly diagnosed AML, 14 of whom had BM blast counts30%. The overall response rate was 47%. Complete remission, partial remission, and hematologic improvement were achieved by 20, 13, and 13% of patients, respectively. Median overall survival was 355 days for the entire cohort, and 532 days for responders. Median time to best response was 95 days, and median treatment duration was 198 days (range = 13-724 days). Grade 3-4 hematologic toxicities comprised predominantly febrile neutropenia (40%) and thrombocytopenia (20%). Febrile neutropenia was the most common cause of hospitalization. Nonhematologic toxicities, consisting of injection-site skin reactions and fatigue (Grades 1-2), occurred in 73% (n = 11) of patients. No treatment-related deaths occurred during the study. The dose and schedule of therapy remained constant in all but four patients. The findings of this study suggest that administration of subcutaneous azacitidine 100 mg/m(2)/day for 5 days every 28 days is a feasible, well-tolerated, and effective alternative to standard induction chemotherapy in elderly patients with AML.