Saliba, Antoine N.

Introduction: Several chemotherapy agents, especially anthracyclines, are associated with the development of non-ischemic cardiomyopathy. When chemotherapy-induced cardiomyopathy (CHIC) is associated with left bundle branch block (QRS >150 ms) and a left ventricular ejection fraction (LVEF) of 35% or lower, cardiac resynchronization therapy (CRT) is often utilized to improve cardiac function and relieve symptoms. Hypothesis: CRT is associated with improvement in left ventricular strain in patients with CHIC. Methods: The study included 22 patients with CHIC and 44 age- and gender-matched controls with other types of NIC who underwent CRT implantation between 2004 and 2017. LVEF, left ventricular global longitudinal strain (GLS), systolic strain rate (SRS), and early diastolic strain rate (SRE) were assessed at baseline and 6-18 months after CRT. CRT response was defined as LVEF improvement by >5% after CRT. Results: CRT responders had a significant improvement in left ventricular GLS as compared to CRT non-responders in the control group, but not in the CHIC group (Table 1). The mean change in LVEF after CRT was similar between the CHIC and control groups (10 ± 10% versus 11 ± 11%, p= 0.67). The mean change in GLS after CRT was also similar between the two groups (-2.15 ± 4.32 versus -3.57 ± 4.02, p= 0.19). The proportion of patients whose LVEF increased by more than 5% was similar between the two groups (59% in the CHIC group versus 68% in the control group, p= 0.46). The mean changes in LV myocardial systolic and early diastolic strain rates were similar between the CHIC and control groups. Mean SRS decreased by 0.13 ± 0.14 in the CHIC group and by 0.34 ± 1.28 in the control group (p=0.45). Mean SRE increased by 0.06 ± 0.18 in the CHIC group and by 0.07 ± 0.22 in the control group (p=0.86). Conclusions: CRT is associated with improvement in left ventricular strain in patients with CHIC. Prospective studies are needed to further evaluate the echocardiographic strain outcomes of CRT in CHIC.

Abstract Abstract Importance: The benefit of routine screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in patients with cancer before cancer-directed therapies is unclear. Herein, we characterize the outcomes of a cohort of cancer patients diagnosed with Coronavirus Disease 2019 (COVID-19) by routine screening in comparison with those diagnosed based on clinical suspicion or exposure history (non-routine screening). Objective: To describe and compare the outcomes of cancer patients diagnosed with COVID-19 on routine screening vs. non-routine screening at a multi-site tertiary cancer center. To identify risk factors for COVID-19-related hospital admission. Design: A multi-site prospective observational study was conducted between March 18 and July 31, 2020. Setting: Three major and 5 satellite campuses of the Mayo Clinic Cancer Center. Participants: Adult patients diagnosed with active cancer within the past five years and confirmed SARS-CoV-2 infection were included. Primary Outcomes and Measures: Clinical and laboratory data were assessed as independent variables. The primary outcome was COVID-19-related hospital admission. Secondary outcomes included intensive care unit (ICU) admissions and all-cause mortality. Results: Between March 18 and July 31, 2020, 5452 patients underwent routine screening in the outpatient setting, 44 (0.81%) were diagnosed with COVID-19. Routine screening detected additional 19 patients from inpatient and pre-procedural settings; 161 patients were diagnosed with COVID-19 based on non-routine screening. The median age of the entire cohort at diagnosis was 54 years, and 95 patients (42.2%) were female. COVID-19 related-hospitalization rate (17.5% vs. 26.7%, p=0.14), ICU admission (1.6% vs. 5.6%, p=0.19), and mortality (4.8% vs. 3.7%, p=0.72) were not significantly different between routine screening and non-routine screening groups. In the multivariable analysis, age ≥ 60 years (odds ratio: 4.4, p=0.023) and an absolute lymphocyte count ≤1.4 × 109/L (odds ratio: 9.2, p=0.002) were independent predictors of COVID-19-related hospital admission. Conclusions and Relevance: The COVID-19 positivity rate was low based on routine screening. Comparing the outcome with the non-routine screening cohort, there was no significant difference. These results led to an important practice change at our cancer center. We currently follow a testing strategy based on symptoms, exposure, risk factors, and clinical judgment. Citation Format: Zhuoer Xie, Antoine N. Saliba, Jithma Abeykoon, Umair Majeed, Daniel Almquist, Julia Wiedmeier-Nutor, Evandro Bezerra, Xavier Andrade-Gonzalez, Ashley Hickman, Karl Sorenson, Sagar Rakshit, Christopher Wee, Sri Tella, Anuhya Kommalapati, Nadine Abdallah, Joshua Pritchett, Mariza De Andrade, Dipesh Uprety, Andrew Badley, Joleen Hubbard, Naseema Gangat, Carrie A. Thompson, Thomas Witzig, Robert R. McWilliams, Konstantinos Leventakos, Thorvardur R. Halfdanarson. Outcomes of COVID-19 in patients with cancer: Results of a prospective observational comparison of routine screening strategy versus testing based on clinical suspicion [abstract]. In: Proceedings of the AACR Virtual Meeting: COVID-19 and Cancer; 2021 Feb 3-5. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(6_Suppl):Abstract nr S06-03.

AbstractBackgroundSeveral chemotherapy agents are associated with the development of non‐ischemic cardiomyopathy (NIC). When chemotherapy‐induced cardiomyopathy (CHIC) is associated with left bundle branch block (LBBB) and a left ventricular ejection fraction (LVEF) 35% or lower, cardiac resynchronization therapy (CRT) is often utilized to improve cardiac function and relieve symptoms.ObjectiveTo determine the echocardiographic and clinical outcomes of CRT in patients with CHIC.MethodsThe study included 29 patients with CHIC (CHIC group) and 58 patients with other types of NIC (control group) who underwent CRT implantation between 2004 and 2017. The primary endpoints were changes in LVEF, left ventricular end‐systolic diameter (LVESD), and left ventricular end‐diastolic diameter (LVEDD) at 6–18 months after CRT. The secondary outcomes included changes in left ventricular global longitudinal strain (GLS), systolic strain rate (SRS), early diastolic strain rate (SRE), and overall survival.ResultsOut of 29 patients with CHIC, 62.1% received chemotherapy for lymphoma, 13.7% for breast cancer, and 24.1% for sarcoma. The agent implicated in 93.1% of the patients was an anthracycline. Half of the patients had LBBB. The mean baseline LVEF was 28% ± 8%. The mean baseline QRS duration was 146 ± 26 ms. Twenty‐eight patients had post‐CRT follow‐up data. CRT was associated with improvement in echocardiographic outcomes in the CHIC group and the control group. There was no difference in overall survival between the two groups (log‐rank p = .148).ConclusionCRT improves left ventricular function and reverses remodeling in patients with CHIC.

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 Clonal cytopenia of undetermined significance (CCUS) is a newly described entity with a high probability to progress into myeloid disorders upon follow-up (Malcovati et al, Blood 2017). Little data is known on how to effectively treat patients with CCUS. We hereby describe a single institution experience in managing symptomatic CCUS patients. Methods Patients who had CCUS and underwent active treatment were identified after receiving IRB approval. CCUS diagnosis was rendered if patients had non-diagnostic bone marrow biopsy evaluation combined with evidence of pathogenic myeloid somatic mutation using our institution next generation sequencing (NGS) panel (OncoHeme, Mayo Clinic). "Symptomatic patients" is determined by patients who need therapy beyond blood transfusion. Treatment type is based on physicians' choice. Clinical and lab results were collected. Response and progression were graded based on the MDS IWG 2006 criteria. The date of treatment initiation was used for overall survival (OS) and progression (either to myeloid neoplasm or worsening cytopenias) free survival (PFS) calculation. Stata 14.1(StatCorp) was used for data analysis. Results 1) Cohort characteristics: Between 2015 and 2020, 24 patients met inclusion criteria with median age of 72 years (range: 24-87). Twenty (83%) were men. 15 (63%) were white, 1 (4%) African American, 1 (4%) Native American and 7 unknown (33%). Eighty percent had ECOG PS≤1. Four (17%) patients had prior other hematology disorders and 3 (13%) had solid tumor. Two (8%) patients had previous radiation therapy, 2 (8%) received chemotherapy and 1 (4%) received allogeneic stem cell transplantation. At the time of treatment, the median of hemoglobin was 8.9 (range 6.8-13.7) g/dL, white blood cell 2.9 (range 1.4-12.3) *109/L, and platelet 76 (range 8-407) *109/L. Red blood cell (RBC) and platelet transfusion dependency rate were 54% and 29%, respectively. We identified 23 different mutations. Most common mutations occurred in SRSF2 (N=5, 21%), TET2 (N=5, 21%), U2AF1 (N=5, 21%), and TP53 (N=4, 17%). Ten (42%) patients had 1 mutation, and 14 (58%) had ≥2 mutations. Treatment included hypomethylating agents (HMA) (N=10, 42%), growth factors (N=11, 46%), steroid (N=4, 17%), testosterone (N=2, 8%), cyclosporine (N=2, 8%), rituximab (N=1, 4%), immunoglobulin (N=1, 4%), vitamin B12 and iron (N=1, 4%). Seven (29%) patients received ≥2 treatments. Median follow up duration was 17.5 months (range 8.9-26.1). Median time from the diagnosis to treatment was 2.1 months (range 0-26.8). 2) Molecular correlation with response The overall response rate (RR) was 50% (hematological or symptomatic improvement). Most responders (67%) were treated with HMA (p=0.013). HMA treatment effect was not significantly associated with DNA methylation genes (DNMT3A, IDH1, IDH2 and TET2, all p>0.05). The RR was 100% for the three patients with IDH1 mutation (treated with HMA, steroid and erythropoietin stimulating agent (ESA), respectively). The RR was 100% for the 3 patients with ZRSR2 mutation (2 HMA, 1 testosterone). The RR was 0% for 3 patients with SF3B1 mutation (1 testosterone and ESA, 1 vitamin B12 and iron, and 1 HMA). The number of mutations had no impact on RR (p=0.41). Table demonstrates the RR for each treatment. 3) Survival and progression outcome At the last day of follow up, RBC and platelet transfusion dependency rate were 38% and 25%, respectively. The median PFS was 16.9 months (95% CI: 7.5-65.3). Six patients (25%) progressed to myeloid malignancy with 4 myelodysplastic syndrome (MDS) and 2 acute myeloid leukemia (AML). Five patients progressed with worsening cytopenias. Among the 4 MDS patients, they had SF3B1, TET2, and ASXL1 mutations at the diagnosis of CCUS. Within the 2 AML pts, 1 had RUNX1 mutation, 1 had BCOR, DNMT3A, PHF6, RUNX1, SF3B1, STAG2, and TET2 mutations at the diagnosis of CCUS. The median OS was not reached with an estimated 2 year OS 77%. Three (13%) patients progressed with cytopenia and died. Their NGS at CCUS diagnosis showed ASXL1, TP53 and U2AF1 mutations, respectively. Conclusion Patients with CCUS responded to available treatments used for myeloid diseases. HMA were effective in this cohort. Mutation profile may have an impact on treatment response. Studies of larger cohorts are needed to validate our findings. Additionally, development of response and progression criteria would be helpful for such patients for reporting treatment outcomes. Disclosures Shah: Dren Bio: Consultancy.

11006 Background: Interest in pursuing a career in oncology has decreased among internal medicine residents completing an inpatient oncology rotation. Over several years, our institutional data at Indiana University School of Medicine reflected lower resident satisfaction with the oncology inpatient ward rotation compared to other rotations. Methods: A hybrid model of inpatient consultations and outpatient clinics replaced the traditional inpatient oncology rotation at our institution. Over a six-month period preceding and following the change in format, residents completed anonymous rotation assessments and rated their experiences on a 5-point Likert scale (low 1 to high 5). Areas assessed included: patient load, educational value of patient mix, quality of didactics and teaching, quality of patient care delivery, adequacy of time for reading, and overall educational quality of the rotation. Results: The hybrid oncology rotation (8 respondents out of 10 residents approached) was rated as significantly superior to the traditional ward format (15 respondents out of 16 residents approached) in six out of eight areas. Improvements in the perceived quality of patient care delivery (p=0.139) and quality of didactics (p=0.058) were also observed without reaching statistical significance. The balance of inpatient and outpatient experiences with the hybrid rotation was highly rated (4.5 ± 0.5). Conclusions: The implementation of a hybrid oncology rotation was associated with perceived improvement in educational value, patient mix, and time for reflection and study without apparent compromise in the quality of patient care delivery. [Table: see text]