Andrade-Gonzalez, Xavier

Background: Elevated serum ferritin (SF) is common in patients with myelofibrosis (MF) given the frequent red-cell transfusion requirements and impaired iron metabolism. The dysregulation of iron metabolism is associated with increased hepcidin levels which predict for inferior survival in patients with MF (Pardanani et al AJH 2013). High pre-transplant SF negatively impacts overall survival and non-relapse mortality in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) for hematological malignancies (Chee et al BMT 2017 & Yan et al 2018). However, the impact of elevated pre-transplant SF specifically on post-alloHCT outcomes has not been described in MF. Methods: We conducted a retrospective study of patients with MF undergoing allo-HCT at Mayo clinic Rochester, Arizona, and Florida from January 1st 2012 - December 31st 2019. We abstracted demographic and outcome variables to evaluate the impact of pre-transplant ferritin levels on post-transplant outcomes. We used a Receiver Operand Characteristic Curve to identify a pre-transplant serum ferritin (SF) of ≥ 1,123 ng/mL as the cutoff which best correlated with poor survival. Results: We identified 67 patients with MF who underwent allo-HCT during the study period with readily available data. Patients with a pre-transplant ferritin ≥ 1,123 ng/mL (n=18) had a median age of 59.4 years and were predominantly male (n=9, 50%) with primary myelofibrosis (n=12, 67%), had a DIPSS-plus int-2 (n=10, 56%) and high (n=6, 33%) risk categories and received a reduced-intensity conditioning (n=14, 78%) from a matched-unrelated donor (n=7, 50%) Table1. Patients with SF ≥ 1,123 ng/mL had a worse overall survival (OS) (median OS= 12.64 months [95%CI=6.08-19.20 months] vs. not-reached (NR) p=0.001). Patients with elevated SF had an increased non-relapse mortality (NRM) rate at 6 months (16.7%, [95%CI=0.4-37.2%]) vs 8.2%,[95%CI= 2.6-18.1%] p=0.021) and 12 months (33.3% [95%CI=13.0-55.4%] vs 10.4% [95%CI=3.8-21.0%] p=0.021) Patients with ≥ 1,123 ng/mL SF had a non-statistically significant higher rate of acute graft-vs-host disease grades 3-4 (28% vs 12.2% p=0.13) but similar rates of moderate to severe chronic graft-vs-host disease (31% vs 28% p=0.78). In the univariate analysis, SF ≥1,123 ng/mL and a Hematopoietic stem cell transplant comorbidity index (HCT-CI) ≥3 were associated with an increased risk of mortality (Hazard ratio [HR]=4.18 [95%CI=1.64-10.62] p=0.003] and HR=4.42 [95%CI=1.70-11.46] p=0.003, respectively). Both retained significance in multivariate analysis SF ≥1,123 ng/mL (HR= 2.80 [95%CI= 1.0-7.6], p=0.04)] and HCT-CI score ≥ 3 (HR 3.10 [95%CI= 1.12-8.62, p=0.03]) after adjusting for age, DIPSS-plus score, conditioning regimen intensity, donor type, CMV risk, prior use of ruxolitinib, and ABO mismatch. We grouped the patients into low, intermediate and high risk categories using SF level and HCT-CI scores as detailed in Figure 1. The risk category based on SF and HCT-CI was statistically significant in impacting OS and NRM in this cohort. The 12 month OS rate was lower in the high risk category (44.4% [95%CI= 13.6%-71.9%]) when compared to the intermediate (64.6%, [95%CI=39.7%-81.3%]) and low risk (91.9%, [95%CI= 76.9%-97.3%], p=0.0002) categories. Similarly, the 12 month NRM rate was higher in the high risk category (44.4%, [95%CI=11.0%-74.2%]) when compared to the intermediate (25%, [95%CI=8.7%-45.5%]) and low risk (5.3% [95%CI=0.9%-15.9%], p=0.0046) categories. Conclusion: In patients undergoing allogeneic SCT for myelofibrosis, serum ferritin ≥ 1,123 ng/mL is a predictor of high NRM and inferior OS. Combining ferritin serum levels with HCT-CI may help in better patient selection for allo-HCT in MF population. Larger patient cohort is warranted to confirm our findings. Disclosures Kharfan-Dabaja: Daiichi Sankyo: Consultancy; Pharmacyclics: Consultancy. Shah:Dren Bio: Consultancy.

Introduction Immune-mediated hematologic disorders are relatively rare but potentially life-threatening immune-related adverse events (irAE) with immune checkpoint inhibitor (ICI) therapy (Shiuan, Beckermann et al 2017). The management strategy often relies on systemic corticosteroids and other immunosuppressant agents in steroid-refractory cases (Brahmer, Lacchetti et al 2018). We hereby describe our institution's experience in diagnosing and managing immune-related hematologic adverse events (ir-h-AE). Methods We retrospectively searched the electronic health record for all ir-h-AE diagnosed by treating providers and confirmed by study authors between 2015 and 2020. The search included patients on ICI and the following conditions: immune-related neutropenia (IRN), autoimmune hemolytic anemia (AIHA), cold agglutinin disease (CAD), immune thrombocytopenia (ITP), immune-related pancytopenia, aplastic anemia (AA), and pure red cell aplasia (PRCA). For AIHA, PRCA, and CAD, partial response (PR) was defined as hemoglobin greater than 10 g/dL but < 12 g/dL and 2 g/dL above the nadir without blood product transfusion. Complete response (CR) was defined as hemoglobin of ≥ 12 g/dL and 2 g/dL above the nadir without blood product transfusion (Peñalver, Alvarez-Larrán et al. 2010). For ITP, CR was defined as platelet count ≥ 100 × 109/L and absence of bleeding. PR was defined as platelet count ≥ 30 × 109/L and ≥ two-fold increase from the baseline count and absence of bleeding (Gómez-Almaguer, Tarín-Arzaga et al. 2013). For IRN, CR was defined as absolute neutrophil count (ANC) ≥ 1500/ mm3 on 2 consecutive measurements separated by 7 days; PR was defined as ANC ≥ 500/ mm3 sustained over 7 days. JMP® 14.1 was used for data analysis. Results Seventeen patients were identified, 9 (52.9%) of whom were female (table 1). Median age was 68 years (range 26-78). The most common pre-existing malignancies were melanoma (6 patients, 35.3%), non-small cell lung cancer (4 patients, 23.5%), and gastrointestinal cancer (3 patients, 17.6%). The ir-h-AE included 7 patients (41.2%) with warm AIHA, 4 (23.5%) with ITP (1 had immune-related pancytopenia that resolved with ITP persisting), 3 (17.6%) with IRN, 1 with AA, 1 with CAD, and 1 with PRCA and mild ITP. All patients had received an ICI dose within 60 days of diagnosis (range 3-52 days, median 18 days). Only 1 patient had a concomitant chronic autoimmune disorder (antinuclear antibody-positive arthritis). Four patients (23.5%) were receiving chemotherapy. Sixteen patients (94.1%) required treatment and received corticosteroids. Eight out of 15 evaluable patients (53.3%) responded to corticosteroids only. Another 4 responders (26.7%) required additional therapies including intravenous immunoglobulins (IVIG) (4, 23.5%) and/or rituximab (4, 23.5%). Overall response rate was 71.4% for AIHA and 100% for IRN. ITP was likely underrepresented in our cohort, and the response rate of 66.7% is likely lower than the response rate in clinical practice. This could be related to the fact that many mild thrombocytopenia cases are not further evaluated in clinical practice. None of our patients died from the sequelae of an ir-h-AE. Two patients (11.8%) died within 30 days of ir-h-AE diagnosis (disseminated intravascular coagulation likely due to the underlying malignancy and sepsis from bacterial pneumonia). At the time of ir-h-AE diagnosis, the malignancy was showing evidence of response in 9 patients (52.9%), progression in 6 patients (35.3%), and stability in 2 patients (11.8%). ICI therapy was permanently discontinued in 9 patients (52.9%) and temporarily held in 6 patients (35.3%). Three of the 5 patients (60%), who were rechallenged with ICI therapy, had recurrence of the same ir-h-AE (AIHA) with adequate response to therapy. Non-hematologic irAE (7 patients, 41.2%) included 3 patients with hepatitis, 2 with thyroiditis, 2 with pneumonitis, 1 with colitis, and 1 with dermatitis. Conclusion Our clinical experience with ir-h-AE highlights the importance of exercising vigilance in assessing the hematologic parameters of patients receiving ICI therapy. While relatively rare, ir-h-AE may impact the clinical course of patients with cancer and their eligibility for therapies that have the potential of offering durable control of the underlying malignancy. ir-h-AE respond to classical therapies including corticosteroids, IVIG, and rituximab. Disclosures Block: Merck: Research Funding; Bristol-Myers Squibb: Research Funding; Genentech: Research Funding; Pharmacyclics: Research Funding; Marker Therapeutics: Research Funding; Transgene: Research Funding; Immune Design: Research Funding. Kottschade:Bristol-Myers Squibb: Consultancy, Research Funding.

Background Patients with Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (MF), have a significant risk of venous thromboembolism (VTE). We aim to determine the trends in annual rates of VTE-related admissions, associated cost, length of stay (LOS), and in-hospital mortality in patients with MPN. Methods We identified patients with PV, ET, and MF from the Nationwide Inpatient Sample (NIS) database from 2006 to 2014 using ICD-9CM coding. Hospitalizations where VTE was among the top-three diagnoses were considered VTE-related. We compared in-hospital outcomes between VTE and non-VTE hospitalizations using chi-square and Mann–Whitney U-test and used linear regression for trend analysis. Results We identified 1,046,666 admissions with a diagnosis of MPN. Patients were predominantly white (65.6%), females (52.7%), with a median age of 66 years (range: 18–108). The predominant MPN was ET (54%). There was no difference in in-hospital mortality between groups (VTE: 3.4% vs. non-VTE: 3.2%; p = 0.12); however, VTE admissions had a longer LOS (median: 6 vs. 5 days; p < 0.01) and higher cost (median: VTE US$32,239 vs. 28,403; p ≤ 0.01).The annual rate of VTE admissions decreased over time (2006: 3.94% vs. 2014: 2.43%; p ≤ 0.01), compared with non-VTE–related admissions. Conclusion In our study, VTE-related admissions had similar in-hospital mortality as compared with non-VTE–related admissions. The rates of hospitalizations due to VTE have decreased over time but are associated with a higher cost and LOS. Newer risk assessment tools may assist in preventing VTE in high-risk patients and optimizing resource utilization.