ALBERT

Description: Background: Hematopoietic stem cell transplantation (HCT) remains the most effective postremission therapy for high-risk acute myeloid leukemia (AML). FMS-like tyrosine kinase3 (FLT3) mutations occur in about 30% of patients with cytogenetically normal AML. FLT3-ITD (internal tandem duplications) mutations are associated with short-lived remissions and poor outcomes. These adverse effects can be offset by allogeneic HCT in first complete remission (CR1). We carried out this study to get a real world perspective on feasibility of allogeneic HCT in CR1 for FLT3-ITD mutant AML patients. Methods: The Mayo Clinic AML database was queried for all patients that had tested positive for the FLT3 ITD, from January 2003 to December 2014. 75 patients were identified, of which 28 (37%) underwent allogeneic HCT in CR1. 12 were excluded as they were transplant ineligible from an age standpoint, 6 patients actually had MDS and 2 were excluded for primary induction failure. Clinical and outcomes data were abstracted retrospectively. Results: 29 patients were included in the final analysis, with a median age of 57 years (range 21-68), 38% males. Median time from diagnosis to last follow up was 339 days. 24(83%) had normal cytogenetics. 26(90%) received treatment with anthracycline + cytarabine based therapy, 3(10%) were enrolled on a clinical trial. 25(87%) patients went on to receive consolidation therapy. 22 (75%) of the patients relapsed after achieving a CR1, with a median time to relapse of 134 days (range 27-1710 days). Only 8 (26%) of the 22 patients were able to achieve a CR2 with salvage chemotherapy, of which 6 (75 %) successfully underwent allogeneic HCT.2 (25%) out of 8 patients received FLT3 inhibitor in 1st relapse. We then assessed the reasons why relapsed patients did not undergo HCT in CR1. The most common being; relapse during evaluation/work up for HCT in 8(27%) patients, 5 (17%) had comorbidities that precluded HCT, 3 (10%) were never referred for HCT due to personal preferences. At last follow up 19(65%) patients were dead. Conclusion: While allogeneic HCT is an effective consolidative strategy for FLT3 ITD mutant AML patients, in the real world, a large number are not transplanted in CR1 due to delays in donor search and transplant scheduling strategies resulting in disease relapse. Effective strategies to avoid delays in scheduling, rapid donor searches and the use of alternative donor sources are much needed for these patients. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Description: Background: The use of social media is expanding in medicine. More and more healthcare professionals, patients and advocates are using social media as a common platform to enhance communication. Methods: Each year American Society of Hematology (ASH) creates a hashtag (#) followed by year of the annual meeting (e.g. ASH 2014 had this hashtag: #ASH14) on Twitter. We conducted a retrospective study of annual meeting's hashtag use on Twitter for past 4 annual meetings using data from Symplur, LLC. Symplur is an online forum offering analytics of the global Twitter based conversations. Following hashtags were used for analysis, #ASH11, #ASH12, #ASH13 and #ASH14. Results: Overall there is an increasing trend for use of annual meeting's hashtag (see table 1). Last year's meeting generated over 72 million impressions. Number of tweets being sent out is doubling every year. More twitter users are engaging in conversations than the year before using annual meeting's hashtag. Last year almost 4000 individual twitter accounts were used during the annual meeting. Number of tweets per participant has stayed relatively constant over past four years. @ash_hematology remains the most commonly mentioned twitter handle every year since 2011. In 2014 itself, @ash_hematology was mentioned over 2000 times. Conclusion: Twitter is a very powerful tool that amplifies the content of scientific meetings. Use of twitter using meeting's hashtag is increasing every year at annual ASH meetings. This analysis provides a snapshot of twitter activity at the conference. Avenues for further research are: trend identification, "influencer" identification, and qualitative analysis. Interdisciplinary research should focus on evaluation methods that can assess the quality, value, and impact of tweeting. Table 1. Year Impressions Tweets Participants Average tweet per participant 2011 12,255,646 3123 606 5 2012 18,153,786 5,094 870 6 2013 30,018,580 12,233 1942 6 2014 72,433,270 24,185 3977 6 Disclosures No relevant conflicts of interest to declare.

Description: Introduction Development of anti-CD38 monoclonal antibody therapies (MoABs), including daratumumab and isatuximab, have drastically changed the therapeutic landscape for management of relapsed and/or refractory multiple myeloma (RRMM). However, there is a paucity of information regarding response to treatment after progression on CD38 MoABs. This collaborative research study (MAMMOTH: Monoclonal Antibodies in Multiple Myeloma: Outcomes after Therapy Failure) investigates the therapeutic choices and outcomes of subsequent treatments after refractoriness to MoABs. Methods Patients from 14 US academic institutions with diagnosis of MM and refractory to daratumumab or isatuximab, administered alone or in combination, were evaluated. Patients were considered refractory to a CD38 MoAB if treated with at least 4 weeks of therapy and had evidence of progressive disease (PD) while on therapy or within 60 days after last dose. Time of progression was defined as time zero (T0). Data was collected by electronic platform and submitted to peer-based quality check for completeness and internal consistency. Results Two hundred and seventy-five patients with MM refractory to CD38 MoAB were evaluated; 249 (90.5%) of those patients who received at least one subsequent line of therapy were included in this analysis. The median age at T0 was 65 years (range 27-90) and 54% were male. At the time of diagnosis, 28% had ISS stage III disease and 29% had high-risk cytogenetics. Patients were heavily pre-treated at T0 with a median of 5 lines of therapy (range 2-17); most (74%) underwent a prior autologous stem cell transplant. The majority of patients were refractory to other anti-myeloma therapies including lenalidomide (78%), pomalidomide (65%), bortezomib (69%) and carfilzomib (45%). In total, 97.1% of patients were exposed to at least one immunomodulatory agent (IMiD) and one proteasome inhibitor (PI), 79.3% were ≥ triple-refractory (refractory to 1 IMiD, 1 PI and 1 CD38 MoAB), while 25.3% were penta-refractory (refractory to 2 IMiDs, 2 PIs and 1 CD38 MoAB). Responses to the next subsequent line of therapy after progression with CD38 MoAB are shown (Table). The overall response rate (ORR; ≥PR) of first regimen post-T0 was 31% with a median progression free survival (PFS) of 3.4 mo and median overall survival (OS) of 9.3 mo. Carfilzomib-based therapy resulted in an ORR of 32% with median PFS 4.2 mo and overall OS of 10.9 mo. The addition of an IMiD to daratumumab yielded an ORR of 37% with median PFS 4.5 mo and OS 12.6 mo. The addition of a PI to daratumumab yielded no responses. Elotuzumab-based therapy had an ORR of 21% with median PFS 2.6 mo and OS 8.3 mo. By multivariate analysis, alkylator-based therapies were found to have the highest ORR (OR 3.1, 95% CI 1.8-5.7, p

Description: History of prior cancer is a widespread exclusion criterion in cancer trials. Up to 80% of NCI-sponsored and 80% of industry-sponsored lung cancer trials exclude patients with a prior cancer. We suspect this exclusion is commonly applied in other cancer trials, although no definitive data exist. Prior cancer is especially common among older patients and those with certain cancer types. Among patients 〉65 years, 15.1% overall have prior cancer. In Multiple Myeloma, the most common plasma cell disorder (PCD), prevalence of prior cancer is as high as 17.4%. Examining the prior cancer exclusion criterion is important because the number of US cancer survivors is large and rapidly growing. Arbitrarily excluding cancer survivors from trials is not evidence-based and exclusion presumably arises from assumptions that higher mortality of patients with prior cancer could hinder study conduct and bias trial outcomes. However, few data exist to support this assumption of higher mortality. In fact, we demonstrated that lung cancer patients with a prior cancer have similar or lower mortality risk, compared to those without prior cancer. In this abstract, we reviewed prior cancer related eligibility criteria in three of the most common PCD (Multiple Myeloma, Amyloidosis and Waldenström Macroglobulinemia) clinical trials sponsored or endorsed by 5 major Co-Operative groups in North America (Table 1). We use descriptive statistics (n, %) and Fisher's exact tests to describe characteristics of trials with and without exclusion criteria. Of 33 trials, 26 (79%) excluded patients with prior cancer as follows - active cancer (12%), within 2-3 years of PCD diagnosis (9%), or within 5 years of PCD diagnosis (55%). Many trials had exceptions to prior cancer exclusion. Specifically, 67% of trials allowed non-melanoma skin cancer, 58% allowed in-situ cervical cancer, 12% allowed early stage prostate cancer. Table 2 shows the association between clinical trial characteristics and prior cancer exclusion. There was no association between prior cancer exclusion and phase of study, transplant studies, or survival end point. Exclusion criteria varied across year of activation (p=0.01); for example, 75% of studies activated 1990-1999 excluded prior cancer, compared to 100% of studies activated after 2010. Type of PCD was marginally associated with exclusion criteria (p=0.08); 74% of Multiple Myeloma trials excluded patients with prior cancer compared to 100% of the Amyloidosis and Waldenström Macroglobulinemia trials. Conclusion: A substantial proportion of potential participants may be excluded from PCD clinical trials because of a history of prior cancer. This practice impacts accrual, generalizability, and fair access to cutting-edge treatments and the highest level of clinical care. As treatment outcomes for other cancers continue to improve, it is likely that the prevalence of multiple primary cancers will increase. This exclusion criterion is applied widely across studies, including more than two-thirds of those with non-survival endpoints. Our study is the first to examine the prevalence and potential impact of prior cancer exclusion in PCD clinical trials. Using population-based cancer registry data, we plan to undertake further research to understand the appropriateness and ramifications of this standard exclusion policy in PCD cancer trials. Disclosures Collins: Agios: Research Funding; Bristol Myers Squibb: Research Funding; Celgene Corporation: Research Funding; Arog Pharmaceuticals: Research Funding. Devine:Kiadis Pharma: Consultancy. Usmani:Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding; Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy. Anderson:Amgen: Speakers Bureau; Takeda: Speakers Bureau; Celgene: Speakers Bureau. Kumar:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Roche: Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; KITE: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Description: Introduction Proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) have significantly improved survival in patients with multiple myeloma (MM). Refractoriness to PIs and IMiDs results in poor outcomes with a median survival of about 13 months.Daratumumab and isatuximab are CD38-targeting monoclonal antibodies (MoABs) with remarkable activity in relapsed and refractory MM. The outcome of MM patients in US clinical practice who becomes refractory to CD38 MoABs is unknown. The aim of this multicenter, retrospective study is to investigate the natural history of patients with MM who become refractory to CD38 MoABs (Monoclonal Antibodies in Multiple Myeloma: Outcomes after Therapy Failure: MAMMOTH study). Methods We identified patients from 14 academic institutions in the US with diagnosis of active MM and refractory to daratumumab or isatuximab, administered alone or in combination. Patients were considered refractory to CD38 MoAB if treated with at least 4 weeks of therapy and had evidence of progressive disease (PD) while on therapy or within 60 days after last dose. The time when patients met the above criteria of progression was defined as time zero (T0). Data including patient-disease characteristics and all therapies administered before and after T0 were collected with an electronic platform and submitted to peer-based quality check for completeness and internal consistency. For survival outcome analysis, patients were classified into three groups: "Penta-refractory" (refractory to 1 CD38 MoAB + 2 PIs + 2 IMiDs), "Triple-refractory and quad-refractory" (refractory to 1 CD38 MoAB + 1 PI + 1/2 IMiDs, or 1 CD38 MoAB + 1/2 PIs + 1 IMiD), and "Not triple-refractory" (refractory to 1 CD38 MoAB, and not both of a PI and an IMiD). Responses were evaluated using the IMWG criteria. Results Two hundred and seventy-five patients were included in this study; median age at T0 was 65 years (range 27-90). Fifty five percent of patients were males, 52% had IgG isotype, 29% had ISS stage III disease, and 29% had high-risk cytogenetics at diagnosis. Median interval from diagnosis of MM to T0 was 50.1 months (mo) (range 2.5-230.1). Patients received a median of 4 lines of treatment (1-16) prior to the CD38 MoAB-containing regimen; 72% underwent prior autologous transplant. Daratumumab-refractory patients formed a majority (256, 93.1%) of this cohort. Most of the patients were refractory to lenalidomide (77%), pomalidomide (65%), bortezomib (68%), and carfilzomib (47%). Seventy patients (25.5%) were "penta-refractory" and 148 (53.8%) were "triple-refractory and quad-refractory". Median follow-up from T0 for survivors was 10.6 mo (range 1.9-42.3 mo). The median overall survival (OS) from T0 for the entire cohort was 8.6 mo (95% C.I. 7.2-9.9); OS for the groups based on refractoriness to prior treatments are shown (Figure). Two hundred and forty-nine patients (90.5%) received at least one line of treatment after T0, (median 2, range 1-10). The response rates and depth of responses to each line of treatment post T0 are shown (Table). Among patients who received ≥ 1 subsequent treatment, the median PFS and OS from T0 were 3.4 (95% C.I. 2.8-4.0) mo and 9.3 (95% C.I. 8.1-10.6) mo, respectively; the median OS for the 26 patients who received no further treatment was only 1.3 (95% C.I. 0.6-1.9) mo. By multivariate analysis, penta-refractoriness (HR 2.4, p

Description: Background: Sickle cell disease (SCD) is a common hemoglobinopathy, characterized by vaso-occlusive crises and affects over 100,000 people in United States. It afflicts long-lasting organ damage with a spectrum of clinical severity. Median survival for SCD is shortened to the 6th decade of life despite advances in medical care (Elmariah et al Am J Hematol 2014). Allogeneic stem cell transplant (SCT) is a potentially curative option and is increasingly considered in patients with severe symptomatic SCD. The use of SCT is limited by donor availability and treatment related complications. Several advancements in conditioning regimen and use of alternate donor source have favorably impacted the feasibility of this approach. We identified SCT performed for sickle cell disease in the Healthcare Cost and Utilization Project National Inpatient Sample (HCUP-NIS) from 2002-2014 in an attempt to identify hospitalization outcomes, factors affecting length of stay and healthcare utilization. Methods: HCUP-NIS is a 20% stratified sample of all discharges from hospitals across 46 states in the United States and incorporates weighting algorithms to predict nationwide estimates. We used International Classification of Diseases, Ninth Revision (ICD-9) procedure codes to identify HCT hospitalizations {Bone marrow (BM):41.02, 41.03, Peripheral blood (PB): 41.05, 41.08 and Cord blood (CB): 41.06} for sickle cell disease (282.5,282.6X -282.6X). We excluded patients who underwent SCT for indications other than SCD. Surveyfreq was used to calculate proportions and surveymeans was used to calculate median length of stay and hospital charges. Kruskal-Wallis test was used for non-parametric data. Chi-square for categorical data frequency, P value of 〈 0.05 was statistically significant. All analysis was performed using SAS 9.4. Results: Outcomes were analyzed from a total of 742 hospitalizations for SCT from 2002-2014 (table 1). Median age for stem cell transplant was 9 years. GVHD occurred in 14% of stem cell transplants. Overall, in-hospital mortality was low at 2.6% while mortality in patients who developed GVHD was 14%. Bacterial infections (including C.difficile) occurred more commonly than viral or fungal infections (table 2). Patients who developed graft vs host disease (GVHD) were also more likely to have bacterial, viral and fungal infections than those without. Pain crisis was noted in 9% of total admissions while stroke occurred in 6%. Median length of stay (LOS) was 35 days and median charges were $359,646. If GVHD developed, median LOS increased to 54 days while median charges increased to $712,324. Similarly, bacterial sepsis was associated with a longer median LOS of 63 days while median charges increased to $626,986 (table 3). Conclusions: The rate of inpatient mortality with SCT in sickle cell disease is lower than the overall inpatient mortality rate for allogeneic SCT (7%; Godara et al bbmt 2018), indicating a favorable outcome for these patients. Infections do occur commonly during the course of hospitalization, especially in association with GVHD. Length of stay is adversely impacted by occurrence of GVHD, bacterial sepsis, C.difficile infection and viral infections. While we are limited by duration of follow up in our study, these patterns suggest some essential modifiers for inpatient morbidity and mortality, therefore require validation in a large prospective study. Disclosures No relevant conflicts of interest to declare.

Description: Background: Acute graft versus host disease (aGVHD) is the leading cause of morbidity and mortality following allogenic hematopoietic cell transplantation (HCT). Corticosteroids are the first line treatment although

Description: Background and objective: Blood loss associated with total lower-extremity joint arthroplasty (TJA) often results in postoperative anemia and need for red blood cell transfusions (RBCT). We report the results of a quality improvement initiative to improve blood management and decrease transfusions in patients undergoing TJA in one tertiary hospital. Methods: Pre and post analysis after the implementation of a multifaceted intervention which included preoperative assessment for anemia, use of tranexamic acid, discouragement of autologous pre-operative blood collection and institution of more restrictive RBCT protocols. The results were stratified into three periods: I - pre-interventional (01/01/2013 -09/30/2013); II - peri-interventional (10/01/2013 -04/30/2014); and III - post-interventional (05/01/2014 -12/31/2014). We used fractional logistic regression with robust standard errors and regression modeling was configured using a segmented, or "piecewise", approach in which slope coefficients in each period were estimated. Results: During the study period 2511 patients underwent surgery. Compared with the pre-intervention period, the total number of RBC units transfused decreased from a total of 587 in the pre- to 107 in the post-intervention period (81.8% decrease). The percentage of patients receiving transfusion declined from 36.7% in pre-implementation period to 8.8% to post-intervention period. Depending upon the costing methodology used, annualized savings in RBC expenditure between time period 1 and 3 ranged from a low of $108,000 using the acquisition cost per unit (~$225/unit) to $480,000 when using activity based costing (~$1000/unit). Mean length of stay (days) and 30-day readmission rates remained stable during the study period. Conclusions: A multidisciplinary approach with proactive involvement of all the interested parties can be successful and sustainable in reducing RBCT and its associated costs, in patients undergoing TJA. Disclosures No relevant conflicts of interest to declare.

Description: Introduction: Approximately 1.5% of population will be diagnosed with leukemia in their lifetime (SEER Cancer Statistics Review). Diagnosis of acute leukemia has an overwhelming effect on the patient and their families. Besides the diagnosis, effect of chemotherapeutic agents and agony over the ultimate outcome can also affect emotional-behavioral wellbeing. Evolution of depression as a disorder, along the course of acute leukemia has been reported in the past (David et al Procedia Soc & Behav Sci 2014). We investigated the prevalence of mental health disorders in hospitalized patients admitted with acute leukemia diagnosis utilizing Healthcare Utilization Project National Inpatient Sample (HCUP NIS), 2002-2014. HCUP-NIS is the largest publicly available all-payer inpatient health care database in the United States, and is a 20% stratified sample of all hospital discharges. Methods: We identified hospitalizations for acute leukemia using ICD-9 codes (203.XX, 204.XX, 205.XX, 206.XX, 207.XX and 208.XX) in the NIS database. We included patients with a primary diagnosis of acute leukemia (myeloid, lymphoid and plasma cell leukemia) including admissions for inpatient chemotherapy and/or complications requiring hospitalization. Similarly, ICD-9 codes were used to identify patients with mental health disorders of interest (ADHD, adjustment disorder, alcohol abuse, anxiety disorder, mood disorders, personality disorders, schizophrenia, substance abuse, childhood disorders). "Surveyfreq" was used to calculate proportions while "Surveymeans" was used to calculate median length of stay and hospital charges. Cochran-Armitage test was used to analyze trends; Kruskal-Wallis test was used for non-parametric data. We used chi-square for categorical data frequency, P value of 〈 0.05 was considered statistically significant. All analysis was performed using SAS 9.4. Results: We identified a total of 59,223 patients with mental health disorders (18.4%) out of a total of 321223 hospitalizations for acute leukemia (table 1). Median age for patients with mental health disorders is 56 years. Mood disorder was most prevalent at 8% followed by anxiety disorder at 6%. Within all mental disorders, mood disorders comprised 44% of all cases followed by anxiety disorder at 32% (figure 1). Over 60% of mental health disorders were in patient age group above 50 years (figure 2). Prevalence of mental health disorders has increased from 10% to 28% between 2002 and 2014 (figure 3). Prevalence of anxiety disorder has increased 6 fold between 2002 (2%) and 2014 (12%). It is unclear if this change is due to an actual increase in the prevalence of this condition or better recognition of mental health disorders leading to better coding. Median length of stay (LOS) is significantly longer in patients with mental health disorders compared to those without (18 days vs 9 days respectively). Median charges for hospitalization are also significantly increased in patients with mental health disorders than those without ($119,245 vs $62,132 respectively). Conclusion: Mental health disorders are common in patients with acute leukemia. One in four patients (28%) in 2014 had a mental health disorder compared to 9% in 2002. Given the retrospective nature of our study, it is difficult to determine if this is an actual increase in the incidence and prevalence of mental health disorders or if better recognition and medical coding contributes to this finding. Our study shows a disproportionate burden of mental health disorders in patients above the age 50, which constitutes the majority of the patients diagnosed with acute leukemia. Use of mental health screening tools in this population could provide an avenue for recognition and possible early intervention. Given the retrospective nature of our study, these findings need to be validated in a prospective patient population. Disclosures No relevant conflicts of interest to declare.