ALBERT

Description: Background: Aberrant epigenetic modifications, fundamental to the pathogenesis of MDS, provide rationale for the use of the so-called hypomethylating agents, decitabine (DAC) and azacitidine (AZA). As depletion of DNA methyltransferase 1 (DNMT1) by these agents is S-phase dependent, episodic dosing used in common practice (SD-DAC; 20 mg/m2 x 5 days, every 28 days, SD-AZA; 75 mg/m2 x 5-7 days, every 28 days) affects only a fraction of the malignant clones. Alternative dosing schedules of decitabine with lower doses given more frequently (LD-DAC; .1-.2 mg/kg SC once/twice weekly) may decrease toxicity and increase response rates by improved hematopoietic differentiation and DNMT1 depletion while avoiding cytotoxicity. Data comparing use of very low and standard-dose DAC or AZA are lacking. Methods: We compared response, survival, and toxicities of 242 MDS patients (pts) treated at our institution from 9/06-10/13 with LD-DAC (n=39), SD-DAC (n=17), or SD-AZA (n=186). Response was assessed per International Working Group 2006 (IWG) criteria, progression-free (PFS) from date of response, and overall survival (OS) from diagnosis. Results: There were no significant differences in baseline characteristics, including median age (70 vs. 74 years, P=.93), proportion of patients with ≥5% bone marrow blasts (27% vs. 35%, P=.54), high/very high cytogenetic risk by the Revised International Prognostic Scoring System (IPSS-R, 25% vs. 40%, P=.31), number of pts with comorbidities (44% vs. 29%, P=.38), median time from diagnosis to treatment (14.6 vs. 6.4 months, P=.25) or prior MDS treatment (AZA and/or lenalidomide, 46% vs. 53%, P=.17), between the LD-DAC and SD-DAC groups, respectively. Likewise, the LA-DAC and SD-AZA groups were similar with respect to median age (70 vs. 68 years, P=.15), proportion of patients with ≥5% bone marrow blasts (27% vs. 39%, P=.19), and high/very high cytogenetic risk by the IPSS-R (25% vs. 27%, P=.83). However, pts in the SD-AZA group had a shorter median time from diagnosis to treatment (2.9 vs. 14.6 months, P=.009) compared to LD-DAC. Median treatment duration was longer in LD-DAC pts compared to SD-DAC (9.1 vs. 3.1 months, P=.0008) with a median cumulative dose of 8.4 mg/kg (range 1.2-41.2) and 350 mg/m2 (range 175-975) for LD-DAC and SD-DAC, respectively. Compared to SD-DAC, the LD-DAC group required more frequent dose reductions/delays (67% vs. 20%, P=.004) and experienced more hematologic toxicity (85% vs. 29%, P〈 .0001), respectively. While median time to best response was similar for LD-DAC and SD-DAC (3 vs. 4.1 months, P=.52) there was a trend for higher IWG response rates (30% vs. 18%, P=.06) and lower disease progression rates (18% vs. 41%, P=.06) for LD-DAC compared to SD-DAC. However, this did not translate into a difference in median PFS (11 vs. 7.6 months, P= .34) or OS (23.9 vs. 18.2 months, P=.64, Figure 1). Comparing these results to SD-AZA, while LD-DAC had a longer median treatment duration (9.1 vs. 5.1 months, P=.052) and shorter median time to best response (3 vs. 5.3 months, P=.005) than SD-AZA, response rates were similar (30% vs. 31%, P=.5) and there were no significant differences with respect to median PFS (11 vs. 7.1 months, P=.059) or OS (23.9 vs. 21.1 months, P=.5, Figure 1). Conclusion: Pts treated with the LD-DAC strategy have a response rate at least equivalent to SD-DAC and SD-AZA, though they required more dose adjustments and receive treatment for a longer time period. Survival was similar for all dosing strategies. Very low-dose DAC is an active treatment approach and will be compared to standard-dose DAC and AZA in an upcoming randomized, prospective trial conducted through the MDS Clinical Research Consortium. Figure 1 Figure 1. Disclosures Off Label Use: Subcutaneous administration of very low-dose decitabine in treatment of MDS .

Description: Background: Transitions between inpatient and outpatient settings, which occur frequently with leukemia patients, (pts) are critical junctures at which patient care can become fractured, particularly with respect to medication reconciliation. Attention to adverse drug events, drug interactions, and dose adjustments for organ function can also minimize medical errors and improve patient care, particularly with chemotherapy regimens, antimicrobial agents, and anticoagulation. We evaluated the prevalence of medication discrepancies and the impact of a dedicated oncology pharmacist in an outpatient leukemia clinic on medication interventions. Methods: All pts discharged from the inpatient leukemia service were seen by an oncology-trained pharmacist within 5 business days of discharge as part of routine transitions of care follow up. The pharmacist provided medication reconciliation to assess for medication list discrepancies and identify opportunities for medication-related interventions, including drug interactions, dose adjustments, and therapeutic drug monitoring. All pts were assessed for drug-related adverse events, correct regimen and dose, adherence and medication access concerns. If an intervention was necessary, the pharmacist made recommendations for management to the licensed medical provider. Pharmacist interventions were characterized as "serious" or "not serious" based on established methods (Overhage, J. Am J Health Systm Pharm. 1999). Serious interventions included: drug interactions likely to reduce efficacy or worsen toxicity of chemotherapy, management of anticoagulation in the setting of thrombocytopenia, and management of antimicrobials in pts with neutropenia. Interventions considered "not serious" included: therapeutic drug monitoring for antifungals, recommendations for the management of chemotherapy-induced nausea and vomiting, discontinuation of herbal products and other non-essential agents, and application for grants to minimize pt out-of-pocket costs for critical medications. All medication lists were updated within the electronic medical record following initial interventions. We evaluated associations between endpoints and the following patient and clinical attributes: age, marital status, diagnosis, treatment type (induction, consolidation, salvage, or chronic such as long-term hydroxyurea, tyrosine kinase inhibitors, or ruxolitinib), and disease status (primary, relapsed/refractory, chronic) using Pearson chi-squared or Wilcoxon rank-sum tests. Analyses were stratified by gender, and significance conferred at the 0.1 level. Results: Between November 2017 and March 2018,106 pharmacist-patient visits occurred with 76 distinct pts. Baseline demographics are described in Table 1. Twenty-five pts (33%) were seen more than once. For 26 visits (24%), the encounter was the first outpatient visit following initial induction chemotherapy for leukemia; for 25 (24%) it was the first outpatient visit for subsequent chemotherapy cycles; and for 55 visits (52%) it was the first outpatient visit following an admission for a complication or infection. Medication education and adherence counseling was provided during 93 visits (87%). A total of 173 medication discrepancies were identified and corrected. Sixty-three (36%) discrepancies required additional intervention, of which 22 (35%) were considered serious. In addition, 33 drug interactions were identified, of which 5 were considered serious. Male pts were more likely to have discrepancies if they were newly diagnosed, compared to those that were relapsed/refractory (P=.013). Female pts were significantly more likely to require intervention if they were single (P=.013) or younger (P=.08). No other factors predicted discrepancies or a need for interventions. Conclusion: Leukemia pts discharged from the hospital had extremely high rates of medication discrepancies, particularly during an initial encounter. One third were considered serious. Presence of an oncology pharmacist led to meaningful clinical interventions with the potential to improve patient outcomes and safety. Disclosures Carraway: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Speakers Bureau; FibroGen: Consultancy; Jazz: Speakers Bureau; Novartis: Speakers Bureau. Advani:Glycomimetics: Consultancy; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Novartis: Consultancy. Nazha:MEI: Consultancy. Gerds:Incyte: Consultancy; Apexx Oncology: Consultancy; Celgene: Consultancy; CTI Biopharma: Consultancy. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees.

Description: Introduction: Daratumumab (DARA) is an anti-CD38 human monoclonal antibody FDA-approved for the treatment of multiple myeloma (MM) and has demonstrated efficacy in AL amyloidosis. Infusion-related reactions (IRRs) occur in over 50% of patients treated with DARA, most commonly with the first infusion despite premedication with corticosteroids, antipyretics, antihistamines, and post-infusion corticosteroids. If DARA is tolerated without IRRs, the infusion rate can be escalated in standardized increments to a final infusion rate administered over 90 minutes in patients with MM (Barr et al. Leukemia 2018). Rapid infusions of DARA decrease length of infusion visits, potentially improving patient satisfaction and optimizing healthcare resources. Recent studies showed that DARA is safe and highly effective in treating AL amyloidosis (Khouri et al, Br J Haematol 2018), but no information is available regarding the safety of administering rapid infusions of DARA in patients with AL amyloidosis. We hypothesized that patients with AL amyloidosis, especially those with cardiac involvement, may not tolerate a rapid administration of fluids. Thus, a DARA rapid infusion protocol for patients with AL amyloidosis was implemented at our institution in April 2018. We report findings from the protocol implementation. Methods: A retrospective observational study was conducted to review adult patients with AL amyloidosis who received rapid infusions of DARA from April 2018 to October 2018. Data collected included relevant past medical history, vitals, premedications, infusion rates, and management of IRRs. Patients were eligible for rapid DARA after tolerating two prior doses of DARA at standard infusion rates. Rapid DARA was infused at 200 mL/hr for 30 minutes, then increased to 450 mL/hr for 60 minutes. Protocol premedications included acetaminophen, diphenhydramine, famotidine, and dexamethasone. No post-infusion corticosteroids were required. The first two standard and first four rapid DARA infusions were evaluated for each patient. Results: 27 patients with AL amyloidosis were included in the study with 162 doses of rapid DARA evaluated. Baseline characteristics included age (median 72 years old), gender (55.6% male), diastolic heart failure (59.3%), combined systolic and diastolic heart failures (11.1%), chronic obstructive pulmonary disease (7.4%), asthma (7.4%), and chronic kidney disease (25.9%). 62.9% of patients had cardiac AL involvement and 51.9% had renal AL involvement. 11/27 (40.7%) patients had IRRs to the first infusion of DARA (cycle 1, day 1) requiring hypersensitivity medications. All 27 patients progressed to rapid rate DARA after both initial and subsequent rates were tolerated. 22/27 (81.5%) patients initiated the first rapid DARA with the protocol premedications. Premedication usage decreased by the fourth rapid DARA dose with only 23.1% patients receiving diphenhydramine, 57.7% receiving famotidine, and 38.5% receiving dexamethasone (Figure 1). No patients received post-infusion corticosteroids. There were no clinically significant IRRs with the DARA rapid infusion protocol across all patients, regardless of organ involvement. There were 10 cases of CTCAE grade 2-3 hypertension that did not require intervention. No hypersensitivity medications were required for any rapid DARA doses. 11/11 (100%) patients who experienced IRRs requiring hypersensitivity medications during their first or second standard DARA infusions tolerated rapid DARA administration without recurrence of IRRs. Conclusions: Rapid administration of DARA is safe and well-tolerated in patients with AL amyloidosis, regardless of organ involvement. Patients who experienced an IRR with the initial DARA dose were able to safely transition to the rapid infusion protocol without recurrence of IRRs. Furthermore, decreased premedication usage after tolerance of rapid DARA infusion did not increase IRRs, suggesting premedications can be discontinued to mitigate associated toxicities. Disclosures Anwer: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau. Valent:Celgene corporation: Speakers Bureau; Amgen corporation: Speakers Bureau; Takeda pharmaceuticals: Speakers Bureau. OffLabel Disclosure: Daratumumab for the treatment of AL amyloidosis

Description: Background Blinatumomab is a bispecific T cell antibody construct, that binds and allows CD-3 positive cytotoxic T cells to recognize and eradicate CD19-positive acute lymphocytic leukemia (ALL) blasts. The drug is approved for patient (pts) with relapsed/ refractory (RR) B-cell ALL and those with minimal residual disease (MRD) based on efficacy in clinical trials. We sought to evaluate the safety and efficacy of blinatumomab in the "real world" setting. Methods We conducted a retrospective multicenter study in collaboration with 11 U.S. academic institutions, and evaluated the outcome of RR B-cell ALL pts, who received blinatumomab outside of clinical trials. These pts were evaluated for response, duration of response (DOR), overall survival (OS) from the time of blinatumomab initiation and toxicity. DOR was estimated among pts who had achieved complete remission (CR)/CR with incomplete count recovery (CRi). Survival curves were estimated using the Kaplan-Meier method and compared via log-rank test. Results From December 2014 to May 2019, 239 pts with B-cell ALL were identified. Baseline characteristics are summarized in Table 1. The median age of pts at blinatumomab initiation was 48 years (yrs) (range, 18-85). Sixty-one (26%) pts had Philadelphia chromosome [t(9;22)] positive (Ph+ve) disease. Sixty-one (26%) pts had ≥ 3 prior therapies and 46 (19%) pts had allogeneic stem cell transplantation (allo-HCT) prior to blinatumomab. Twenty-two (9%) pts received inotuzumab ozagamicin prior to blinatumomab. Twenty-nine (12%) pts received blinatumomab in combination with tyrosine kinase inhibitor (TKI). Twelve (5%) pts received blinatumomab for MRD. Response rate (CR/CRi) in pts with RR disease was 61%; 44% had CR with MRD negativity by flow cytometry. Rate of CR/CRi in Ph+ve B-cell ALL was 74.5%. Among 12 pts who received Blinatumomab for MRD, 9 (75%) pts achieved MRD negativity. Overall 113 (48%) pts were successfully bridged to allo-HCT. Median DOR in pts with RR disease was 32.1 months (95% CI; 9.5-not reached [NR]) (Fig. 1a) and when censored at allo-HCT was 14.8 months (95% CI; 5.2-NR) (Fig. 1b). Median OS in pts with RR disease after blinatumomab was 12.7 months (95% CI; 9.2 -17.9) (Fig. 1c) and when censored at allo-HCT was 8.6 months (95% CI; 6.4-11.6) (Fig.1d). Median OS after blinatumomab in RR B-cell ALL Ph+ve pts was NR (59% alive at 2 yr). Among pts who received blinatumomab for MRD, median DOR was NR and 54% sustained MRD negativity at 2 yrs. Median OS was 34.7 months (95% CI; 8.8-34.7) in group of pts who received blinatumomab for MRD. Seven (3%) pts discontinued blinatumomab due to adverse events and 40 (21%) pts had dose interruptions. Cytokine release syndrome (CRS) of any grade (G) was reported in higher number of pts (93 [39%]) compared to clinical trials, though G3-4 CRS appears to be similar (G1-2 [36%], G3-4 [3%]). Forty-four (44%) pts were treated with steroids and 8 (8%) pts required tocilizumab with steroids for CRS. Ninety-three percent of pts had complete resolution of CRS. CNS toxicities were observed in 31 (13%) pts, among them 60% (n= 19) had G3-4 toxicities. Hepatic toxicities were observed in 84 (35%) pts as outlined in Table 1. Six (2.5%) pts died due to blinatumomab induced toxicities. Conclusion: Our real-world data with multicenter collaboration suggest that overall blinatumomab was well tolerated and had led to significant response in pts with RR B-cell ALL. Disclosures Advani: Amgen: Research Funding; Abbvie: Research Funding; Pfizer: Honoraria, Research Funding; Macrogenics: Research Funding; Kite Pharmaceuticals: Consultancy; Glycomimetics: Consultancy, Research Funding. Aldoss:AUTO1: Consultancy; Helocyte: Consultancy, Honoraria, Other: travel/accommodation/expenses; Agios: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria, Other: travel/accommodation/expenses, Speakers Bureau. Podoltsev:Agios Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Research Funding; Astellas Pharma: Research Funding; Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Research Funding; Sunesis Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding; Pfizer: Research Funding; Astex Pharmaceuticals: Research Funding; CTI Biopharma: Research Funding; Celgene: Other: Grant funding, Research Funding; Genentech: Research Funding; AI Therapeutics: Research Funding; Samus Therapeutics: Research Funding; Arog Pharmaceuticals: Research Funding; Kartos Therapeutics: Research Funding. Curran:Incyte: Research Funding; Merck: Research Funding; Gilead: Research Funding. Yang:Agios: Consultancy; AstraZeneca: Research Funding. Mattison:Pfizer: Membership on an entity's Board of Directors or advisory committees. Liedtke:Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; IQVIA/Jazz: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celator: Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Research Funding; Amgen/Onyx: Consultancy, Honoraria, Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees; Agios: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Atallah:Helsinn: Consultancy; Takeda: Consultancy, Research Funding; Jazz: Consultancy; Pfizer: Consultancy; Helsinn: Consultancy; Novartis: Consultancy; Jazz: Consultancy.

Description: Background: RCTs play a key role in advancing treatment for hematologic malignancies and are often a requisite for regulatory approval. To maximize this potential for registration, eligibility criteria for RCTs may be overly restrictive so as to avoid toxicities that may be attributed to the study drug. We hypothesized that RCTs in hematologic malignancies exclude patients (pts) irrespective of adverse events (AEs) that would be expected based on drug class, or that are ultimately observed. Methods: We searchedjournals with an impact factor ≥5 for therapeutic phase II and III hematologic malignancy RCTs in adults published from 01/10 to 01/15. Trial eligibility criteria were extracted from clinicaltrials.gov, the International Standard Randomized Controlled Trial Number (ISRCTN) registry, or the protocol, when available. AEs were collected from package inserts or published manuscripts for the following drug classes: alkylators, antimetabolites, anthracyclines, topoisomerase inhibitors, microtubule inhibitors, proteasome inhibitors, and monoclonal antibodies. Toxicities of these drug classes were compared to corresponding trial exclusion criteria using the exact binomial test. We examined reported AEs occurring in ≥10% of subjects within trials, the threshold applied in medication labels. Poisson distributions, with means = 10% of sample sizes of studies (with exclusion criteria), were assumed in calculating the binomial probability for each AE; we considered AEs relevant to the most commonly used organ function exclusion criteria: hepatic, kidney, cardiac, and neurological. Results: Of 252 full publications identified, 91 (36%) were not RCTs; 27 (11%) were pediatric; 23 (9%) did not meet other inclusion criteria, and 13 (5%) were "kin" publications of the same trial, leaving 98 trials in the final analysis. Of these, 32 (33%) were leukemia trials, 27 (28%) were lymphoma, 34 (35%) were multiple myeloma, and 5 (5%) were myelodysplastic syndromes or myelofibrosis. The majority of studies were phase III (n=77, 79%), multi-center (n=92, 94%), and/or multi-national (n=63, 64%). Of the 98 trials, 12 (12%) contributed pivotal registration data leading to a label change or new approval for 8 drugs. Key trial exclusion criteria were medical comorbidities (e.g. active or prior cancer, previous cardiac conditions, HIV infection, hepatitis, or psychiatric disease, in 97% of studies); inadequate organ function (in 89%), and poor performance status (in 67%). Exclusion criteria relevant to baseline organ function did not reflect established safety profiles, as the proportion of studies excluding pts with specific organ dysfunction was significantly greater than the proportion of drug classes with known hepatic (85/98 [87%] vs. 75%; P=.007), cardiac (73/98 [74.5%] vs. 62.5%; P=.02), and renal (72/98 [73.5%] vs. 50%; P

Description: Background: Younger patients (pts) with acute myeloid leukemia (AML) who enter a remission after intensive induction chemotherapy routinely receive at least one cycle of consolidation therapy with high dose cytarabine (HiDAC). This is commonly administered over a five-day inpatient stay, after which pts are discharged home as their blood counts nadir. It is thus a natural consequence of therapy that readmission for febrile neutropenia (FN) occurs, which can impact measures of quality and value in this population. Precise descriptions of incidence, type, and severity of infection, if identified, are lacking, and thus it is unknown to what standard cancer centers should be held for anticipated readmission. We measured these rates, and attempted to identify predictive factors for readmission. Methods: Adult AML pts ≥ 18 years of age who received at least one cycle of HiDAC consolidation (1000-3000 mg/m2 for six doses) in 2009-2019 were included. Our primary aim was to identify predictive factors for readmission after the first cycle of consolidation chemotherapy. The following pt characteristics and co-morbid conditions were analyzed: age, gender, body mass index (BMI), smoking status, AML cytogenetic risk status, history of diabetes, peripheral vascular disease, cardiovascular disease, chronic pulmonary disease, hepatic impairment, and other cancers. Secondary aims included: estimating rates of all-cause readmissions among all HiDAC cycles, defining the rate of FN readmissions, estimating rates of intensive care unit (ICU) admissions, clinical (e.g., probable pneumonia per imaging) and microbiologically-documented infections, prophylactic (ppx) medications used, and mortality. Statistical analyses interrogated potential risk factors for evidence of association with hospital readmission after the first cycle of consolidation chemotherapy. Results: We identified 182 AML pts who fit inclusion criteria. The median age was 50 years (range 19-73); 55% were female and 45% were male. Statistical analyses revealed no association with readmission after cycle 1 for cytogenetic risk (p=0.85), history of heart failure (p= 0.67), chronic pulmonary disease (p=1), connective tissue disease (p=0.53), cerebrovascular accident (p=0.63), diabetes (p=0.63), gender (p=0.07), history of lymphoma (p=0.53), other solid tumors (p=0.53), liver disease (p=1), myocardial infarction (p=0.71), peripheral vascular disease (p=1), or smoking status (p= 0.52). For 480 HiDAC cycles analyzed (88% at 3000 mg/m2), the overall readmission rate was 50% (242/480), of which 85% (205/242) were for FN. Those readmissions which were not FN were for cardiac complications (chest pain, EKG changes), non-neutropenic fevers or infections, neurotoxicity, bleeding or clotting events, or other symptoms associated with chemotherapy (nausea/vomiting, pain, etc.). Median time to FN hospital admission was 18 days (range 6-27) from the start of HiDAC. Of the 205 FN readmissions, 57% had documented infections. Of these infections, 41% were bacteremia, 23% fungal, 16% sepsis, 12% other bacterial, and 8% viral. Of 480 HiDAC cycles, ppx medications prescribed included: 92% fluoroquinolone (442/480), 81% anti-viral (389/480), 30 % anti-fungal (142/480), and 3% colony stimulating factor (14/480). Only 7% (14/205) of FN readmissions resulted in an ICU admission, and 1% (3/205) resulted in death. Conclusions: Approximately half of patients treated with consolidation therapy following intensive induction therapy can be expected to be readmitted to the hospital. The majority of FN readmissions were associated with clinical or microbiologically documented infections and are not avoidable, however ICU admission and death associated with these complications are rare. Readmission of AML pts following HiDAC is expected, and therefore, should be excluded from measures of value and quality. Disclosures Waldron: Amgen: Consultancy. Hobbs:Amgen: Research Funding; SimulStat Inc.: Consultancy. Advani:Macrogenics: Research Funding; Abbvie: Research Funding; Kite Pharmaceuticals: Consultancy; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Glycomimetics: Consultancy, Research Funding. Nazha:Incyte: Speakers Bureau; Abbvie: Consultancy; Daiichi Sankyo: Consultancy; Jazz Pharmacutical: Research Funding; Novartis: Speakers Bureau; MEI: Other: Data monitoring Committee; Tolero, Karyopharma: Honoraria. Gerds:Imago Biosciences: Research Funding; Roche: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pfizer: Consultancy; CTI Biopharma: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Sierra Oncology: Research Funding. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees. Mukherjee:Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees.

Description: Background: Patients (pts) with hematologic malignancies have an increased risk of venous thromboembolism (VTE) events, driven by both the underlying cancer and cancer treatment. This risk exists even in acute leukemia (AL) in the setting of profound thrombocytopenia and coagulopathies, which can delay VTE diagnosis and complicate management. We evaluated the incidence of VTE in AL pts during an admission for chemotherapy and determined its effect on the duration of hospital stay and likelihood of intensive care unit (ICU) admission. Methods: All pts admitted to the Cleveland Clinic inpatient leukemia service with a diagnosis of acute myeloid (AML), lymphoblastic (ALL), or promyelocytic leukemia (APL) between January 1, 2013 and March 31, 2018 and treated with high-intensity chemotherapy were included. High intensity regimens for AML and APL included infusional cytarabine and an anthracycline with the addition of ATRA for latter and for ALL included Hyper-CVAD and CALBG regimens. Pts were excluded if they were admitted directly to the ICU or were transferred after initiating chemotherapy from another institution. Cases with VTE were defined using specific ICD-9-CM codes [451.1x, 451.2; 451.81, 453.1, 453.2, 453.8, 453.9, 415.1x; and, in addition, 997.2 or 997.3 when coupled with a secondary diagnosis of VTE]. All VTE cases identified through this strategy via an electronic medical record query were additionally validated on subsequent chart review. Pts with a diagnosis of VTE were matched 1:3 based on age, sex, race, and leukemia subtype to pts who did not experience VTE during the incident admission. Pts were also assessed for administration of prothrombotic agents, including: PEG-asparaginase, oral contraceptives, and tyrosine kinase inhibitors. The length of stay for the incident hospitalization and incidence of ICU admission were compared between pts who did and who did not experience VTE. Results: Of the 400 AL pts admitted to the inpatient leukemia service during the study period to receive high-intensity chemotherapy, 10 (2.5%) had a documented VTE during the admission. Baseline characteristics of the 1:3 matched cohorts (AL with and without VTE) are shown in Table 3. The median age of the AL pts who developed VTE was 54.5 years (range, 20-78 yrs), 60% were females, median platelet count at the time of VTE diagnosis was 117,900/mL [(range, 29-476,000/mL); 4 pts had platelet (plt) counts below 50,000/mL, 8 pts had plt below 100,000/mL; 2 pts had normal plt counts], and four pts had bloodstream infections within 7 days of VTE occurrence. By disease breakdown, four had AML, 3 had APL and 3 had ALL. By treatment course, 9 pts were receiving initial chemotherapy 1 pt was receiving salvage therapy. By VTE site, 8 patients had line associated VTE and 2 patients had pulmonary embolism. Five VTE pts were treated with either unfractionated or low molecular weight heparin, 2 underwent IVC filter placement and 3 were untreated. Pts in the VTE group experienced a longer duration of hospitalization compared to those who did not have a VTE event (29.81 vs 23.13 days, respectively, P=.027), and were more likely to be admitted to the ICU compared to those who did not experience VTE (66.7% vs 14.8%, respectively, P=.010). VTE risk was not associated with use of prothrombotic agents (p=.430). Summary and Conclusion: While the incidence of VTE in our patient population was lower than what has been previously reported, it was associated with a prolonged hospitalization and increased risk of ICU admission. The incidence of VTE was not associated with use of thrombotic agents and VTE events occurred in patients with normal plt counts and even in the setting of moderate or severe thrombocytopenia. While it is unclear if early intervention after the diagnosis of VTE affects clinical outcome, the association with increased length of stay and ICU admission can increase healthcare-associated costs in the current environment with increasing focus on value. Further studies are warranted to characterize the risk factors for VTE in AL population. Disclosures Carraway: Novartis: Speakers Bureau; FibroGen: Consultancy; Jazz: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Speakers Bureau; Balaxa: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Advani:Amgen: Research Funding; Novartis: Consultancy; Glycomimetics: Consultancy; Pfizer: Honoraria, Research Funding. Nazha:MEI: Consultancy. Gerds:Incyte: Consultancy; CTI Biopharma: Consultancy; Apexx Oncology: Consultancy; Celgene: Consultancy. Sekeres:Opsona: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Opsona: Membership on an entity's Board of Directors or advisory committees.

Description: Background: Inotuzumab ozogamicin (InO) is an antibody-drug conjugate composed of anti-CD22 antibody conjugated to the cytotoxic agent calicheamicin, which is approved for relapsed/ refractory (RR) B-cell acute lymphocytic leukemia (ALL), based on efficacy demonstrated in a randomized control trial. We sought to investigate the safety and efficacy of InO in the "real world" setting. Methods: We conducted a retrospective multicenter study in collaboration with 11 U.S. academic institutions, and evaluated the outcome of patients (pts) with RR B-cell ALL, who received InO outside of clinical trials. These pts were evaluated for response to InO, duration of response, overall survival (OS) and toxicity. Demographic and disease characteristics were summarized using descriptive statistics. Survival curves were estimated using the Kaplan-Meier method and compared via log-rank test. Duration of response was estimated among pts who achieve complete remission (CR)/CR with incomplete count recovery (CRi). Results: From June 2016 to May 2019, 84 pts with RR-B cell ALL were identified. Baseline characteristics are summarized in Table 1. The median age of pts at InO initiation was 50 years (yrs) (range, 20-87). Twenty-two (27.5%) pts had t(9;22) (Ph+ve) and 6 (7.5%) pts had t(4;11) (MLL gene) chromosomal abnormalities. Nine (11%) and 20 (25%) pts had CNS disease at diagnosis and at relapse, respectively. Median number of therapies prior to InO was 2 (range, 0-7), 40 (48%) pts had ≥ 3 therapies and 23 (27%) pts had allogeneic stem cell transplantation (allo-HCT) prior to InO. Forty (48%) pts received blinatumomab prior to InO. Fourteen (17%) pts received InO in combination with chemotherapy and/ or tyrosine kinase inhibitor (TKI). Overall response rate (CR/CRi) was 63%; 44% had CR with minimal residual disease (MRD) negativity by flow cytometry. Response rate in Ph+ve B-cell ALL was 73%. Twenty-three (27%) pts were successfully bridged to allo-HCT. Median response duration with InO was 11.5 months (mo); 32.5% had sustained response at 2 yrs (Fig. 1a). Median response duration post InO, censored at allo-HCT was not reached (NR) (51% in remission at 2 yrs) (Fig. 1b). Median OS after InO was 11.6 mo and 32% were alive at 2 yrs (Fig. 1c). Median OS post InO, censored at of allo-HCT was 13.6 mo (Fig. 1d). Median OS after InO in Ph+ve pts was NR (71% alive at 1 yr). Forty-nine percent, 27%, 6% and 5% of pts discontinued InO due to progression, allo-HCT, adverse events and maintenance therapy, respectively. Nineteen (30%) pts had dose interruptions. In terms of toxicities, 14 (17%) and 7 (8%) pts had grade (G)1-2 and G3 transaminases secondary to InO, respectively. One pt each had G2 and G3 pancreatitis, respectively. One (1%) and 2 (2%) pts had G2 and G4 veno-occlusive disease secondary to InO, respectively. Two of these pts were treated with defibrotide. Two (2%) pts died due to InO toxicity. A complete description of adverse events are summarized in Table 1. Conclusion: Our real-world data obtained by multicenter collaboration suggest that InO was well tolerated and had significant efficacy in this heavily treated patient population of RR B-cell ALL. Disclosures Liedtke: Celator: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech/Roche: Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; IQVIA/Jazz: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: 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, Research Funding; Caelum: Membership on an entity's Board of Directors or advisory committees; BlueBirdBio: Research Funding; Adaptive: Membership on an entity's Board of Directors or advisory committees; Agios: Research Funding; Amgen/Onyx: Consultancy, Honoraria, Research Funding. Aldoss:Jazz Pharmaceuticals: Honoraria, Other: travel/accommodation/expenses, Speakers Bureau; Agios: Consultancy, Honoraria; AUTO1: Consultancy; Helocyte: Consultancy, Honoraria, Other: travel/accommodation/expenses. Curran:Incyte: Research Funding; Merck: Research Funding; Gilead: Research Funding. Podoltsev:Celgene: Other: Grant funding, Research Funding; Genentech: Research Funding; AI Therapeutics: Research Funding; Agios Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Research Funding; Astellas Pharma: Research Funding; Daiichi Sankyo: Research Funding; Sunesis Pharmaceuticals: Research Funding; Jazz Pharmaceuticals: Research Funding; Pfizer: Research Funding; Astex Pharmaceuticals: Research Funding; CTI Biopharma: Research Funding; Samus Therapeutics: Research Funding; Arog Pharmaceuticals: Research Funding; Kartos Therapeutics: Research Funding; Alexion: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Yang:AstraZeneca: Research Funding; Agios: Consultancy. Mattison:Pfizer: Membership on an entity's Board of Directors or advisory committees. Advani:Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Macrogenics: Research Funding; Glycomimetics: Consultancy, Research Funding; Kite Pharmaceuticals: Consultancy; Abbvie: Research Funding. Atallah:Takeda: Consultancy, Research Funding; Jazz: Consultancy; Helsinn: Consultancy; Novartis: Consultancy; Pfizer: Consultancy; Jazz: Consultancy; Helsinn: Consultancy.

Description: Background: Clinical trial recruitment is hindered by patient (pt), provider, and organizational barriers. The prohibitory impact of specific comorbidity/organ function criteria, however, has not been studied in the AML pt population. While intended to protect pts, trial eligibility criteria, when excessive, exclude pts irrespective of expected toxicities (Statler et al. Leukemia 2017). Yet, research demonstrates adverse events and outcomes are similar among eligible and ineligible AML pts (Statler et al. Blood 2018). We characterized the multi-morbidity prolife of AML pts prior to induction chemotherapy and compared outcomes among those with and without baseline comorbidities/organ dysfunction that have been used in clinical trial eligibility criteria. Methods: Adult (≥18 years) AML pts who received chemotherapy at Cleveland Clinic from 2003 to 2019 were included. The following characteristics were analyzed: age, sex, self-reported race, insurance, etiology of AML, comorbidities, hepatic/renal function tests, left ventricular ejection fraction (LVEF), and corrected QT interval (QTc). AML risk was categorized according to the 2017 European LeukemiaNet (ELN) risk stratification. Univariate associations between dose modifications and pt characteristics were tested using logistic regression. Cox proportional hazards and logistic regression were used to identify significant prognostic factors for overall survival (OS) and complete remission (CR) status per International Working Group criteria. Kaplan-Meier method was used to estimate median OS. Results: Of 1,082 AML pts analyzed, the median age was 60.6 years (IQR: 50.2, 69.1), 53.1% (n=574) were male, 86.8% (n=939) were white, and 45.7% (n=494) had Medicare insurance. A majority (n=680, [62.9%]) had de novo AML, and 55.3% (n=598) had intermediate-risk disease. Pts were treated with: intensive cytarabine-based (n=901 [83.3%]), or non-intensive (low-dose cytarabine or hypomethylating agents (n=181 [16.7%]). Of those with comorbidities, the most common were vascular (n=540 [49.9%]), endocrine (n=272 [25.1%]), and neurological (n=220, [20.3%]) (Tables 1 and 2). With a median follow-up of 12.9 (IQR: 4.67-43.13) months, the median OS for the cohort was 15.1 months (range 0.03-189.25). In multivariate analyses controlling for treatment, age, sex, insurance, number of comorbidities, AML etiology, and ELN risk, the only comorbidity associated with OS was liver disease (HR=1.90, P=.004). However, baseline AST (3xULN vs. normal: HR=1.02, P=.94; 〉3-5x ULN vs. normal: HR=1.42, P=.30.), ALT (3xULN vs. normal: HR=0.76, p=0.45, 〉3-5xULN vs. normal: HR=1.58, P=.23) and bilirubin (1.5xULN vs. normal: HR=1.34, P=.08) were not associated with a worse OS. Minor renal dysfunction was also not associated with OS, when measured by creatinine (1.5xULN vs. normal: HR=1.06, P=.52) or creatinine clearance by Cockcroft-Gault (CrCl 84-60 ml/min: HR=0.95, P=.62). Baseline LVEF abnormalities, though, were associated with increased mortality, and as severity increased the effect size increased in a dose-response fashion (50-40%: HR=1.38, P=.04; 480ms: HR=1.36, P=.04; ≥501: HR=1.72, 95%, P=.001). With the exception of liver comorbidities (OR=0.26, P=.03), our analysis failed to identify significant evidence of association between response and comorbidities/organ dysfunction. Comorbidities and liver function abnormalities were also not associated with dose modifications during AML treatment, while pts with clinically significant renal (CrCl ≤ 30 ml/min) and/or cardiac (LVEF ≤50%) abnormalities at baseline did have a higher odds of a dose reduction in univariate analysis. Conclusions: The majority of AML pts within this cohort (n=953 [88.1%]) presented with at least 1 comorbidity and/or 1 clinically insignificant liver or renal abnormality that could have excluded them from clinical trials. Yet, survival, response, and dose modification outcomes did not significantly differ between pts with and without comorbid conditions or minor liver/renal abnormalities. These results suggest future AML trials may liberalize comorbidity and organ function eligibility criteria, which will likely improve recruitment rates and provide equitable access to investigational products. Disclosures Hobbs: SimulStat Inc.: Consultancy; Amgen: Research Funding. Mukherjee:Bristol-Myers Squibb: Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Projects in Knowledge: Honoraria; Celgene Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Partnership for Health Analytic Research, LLC (PHAR, LLC): Consultancy; McGraw Hill Hematology Oncology Board Review: Other: Editor. Advani:Abbvie: Research Funding; Macrogenics: Research Funding; Pfizer: Honoraria, Research Funding; Amgen: Research Funding; Kite Pharmaceuticals: Consultancy; Glycomimetics: Consultancy, Research Funding. Gerds:Sierra Oncology: Research Funding; Imago Biosciences: Research Funding; Roche: Research Funding; CTI Biopharma: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Pfizer: Consultancy; Celgene Corporation: Consultancy, Research Funding. Nazha:Tolero, Karyopharma: Honoraria; MEI: Other: Data monitoring Committee; Novartis: Speakers Bureau; Jazz Pharmacutical: Research Funding; Incyte: Speakers Bureau; Daiichi Sankyo: Consultancy; Abbvie: Consultancy. Sekeres:Syros: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Millenium: Membership on an entity's Board of Directors or advisory committees.

Description: Background: Determining which AML patients (pts) are "fit" for intensive chemotherapy (IC), both in real-world scenarios and for clinical trial eligibility (particularly as it relates to regulatory indications) is challenging. While age, AML etiology, and cardiac function have been invoked, these oversimplify the clinical assessment and recommendation for IC vs. Non-IC (NIC). We compared baseline characteristics among pts receiving IC and NIC, and evaluated associations between treatment receipt and pt characteristics. Adjusting for treatment received, pts' attributes were further evaluated for association with overall survival (OS). Methods: Adult (≥18 years) AML pts who received IC or NIC at Cleveland Clinic from 2003 to 2019 were included. The following characteristics were analyzed: age, sex, self-reported race, insurance, etiology of AML, comorbidities, hepatic and renal function tests, left ventricular ejection fraction (LVEF), and corrected QT interval (QTc). AML risk was categorized according to the 2017 European LeukemiaNet (ELN) risk stratification. Fisher's exact and Welch's t-tests were performed to compare baseline characteristics. Multivariate logistic and Cox regression were used to identify significant prognostic factors for treatment receipt and OS, respectively. The Kaplan-Meier method estimated distributions of OS, which were compared among pt cohorts using the log-rank test. Classification and regression tree (CART) analysis was performed to characterize the best decision process used to select pts for NIC. Results: Of 1,082 AML pts analyzed, 901 (83.2%) were treated with intensive, cytarabine-based chemotherapy, and 181 (16.8%) with non-intensive (low-dose cytarabine or hypomethylating agents) regimens. As expected, baseline characteristics were significantly imbalanced between groups; pts receiving NIC were more likely to be older (P