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The coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic on March 11, 2020. This novel virus can cause a rapid progression from cough to acute respiratory distress syndrome and death. Cancer patients infected with COVID-19 were reported to have a 39% incidence of severe events, including admission to intensive care unit (ICU), mechanical ventilation, or death. Patients with hematologic malignancies, especially those undergoing treatment, are a particularly at-risk population due to disease-related impairment of the immune system and chemotherapy-induced neutropenia. The goal of this study is to analyze outcomes of COVID-19 infected patients with hematologic malignancies in order to better understand the impact of SARS-CoV-2 on this vulnerable population. Methods We performed a retrospective analysis on 26 COVID-19 positive patients with hematologic malignancies identified at our center. On July 22, 2020, there were 264 COVID-19 positive patients with hematologic malignancies (including our center's 26 patients) reported to the American Society of Hematology Research Collaborative COVID-19 Registry (ASH RC), a global public reference tool. We extracted our patient's data from each category reported to the ASH RC and compared hospitalization, ICU admissions, and mortality rates between our cohort and the remaining 238 cases. Chi-square test was used for analyses. We also performed a subgroup analysis comparing demographics; type and status of hematologic malignancy, as well as COVID-19 directed treatments between our center's patients and the patients reported to the ASH RC. Results Between March and June 2020, a total of 1265 COVID-19 positive patients were hospitalized at our institution. A significantly higher percentage of COVID-19 patients with hematologic malignancies were hospitalized at our institution compared to the ASH RC (61.5% versus 35.3%, P=. 009). There was no difference in ICU admission rate at our center compared to the ASH RC (23.1% versus 30.2%, P=.45). Significantly less COVID-19 directed therapies were administered at our center compared to the ASH RC (46.2% versus 66.4%, P=.041). Our patients received: 7.7% Remdesivir, 11.5% Tocilizumab, 15.4% hydroxychloroquine, 11.5% azithromycin, 0% convalescent plasma, compared to the ASH RC: 1.7% Remdesivir, 5.5% Tocilizumab, 30.3% hydroxychloroquine, 25.6% azithromycin, 4.6% convalescent plasma. Lastly, our institution had a significantly decreased mortality rate compared to the ASH RC (11.5% versus 29.8%, P=.049). Demographics as well as type and status of hematologic malignancy comparing the two cohorts are shown in Table 1. Conclusions In our comparative analysis, we found that our center's patients were hospitalized significantly more than the ASH RC cohort yet had lower mortality rates. These differences were seen despite similar distribution of malignancy types between the two groups. It should be noted that more patients in our cohort were in remission and none presented at initial cancer diagnosis at the time of infection, which may have contributed to better outcomes. The difference in mortality rates may also be attributed to variance in provider experience, higher percentage of patients >80 years of age reported to the ASH RC, and closer patient monitoring at our center due to a higher hospitalization rate. Differences in ICU admissions were not significant, suggesting a similar rate of severe COVID-19 infection between the two cohorts. Our demographics reflect the urban population we serve with more African Americans and Hispanics compared to the ASH RC. The greater number of COVID-19 directed therapies in the ASH RC cohort compared to ours is likely attributed to the use of convalescent plasma, which was not commonly used as COVID-19 directed treatment at our institution. Limitations of our study include a restricted time frame, small sample size, and the possibility of incomplete datasets within the ASH RC, as stated on the registry's website. In conclusion, we recommend close monitoring and a lower threshold for hospitalizing patients with hematologic malignancies in the setting of COVID-19 infection; however, additional prospective studies are needed to confirm our findings, and further investigate the complications and outcomes of SARS-CoV-2 on this at-risk population. Disclosures Ustun: Kadmon: Honoraria. Shammo:Celgene: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau; Onconova: Research Funding; Incyte: Consultancy, Research Funding, Speakers Bureau; Apellis: Consultancy; Regeneron: Consultancy; Novartis: Consultancy; Agios: Consultancy; Sanofi: Speakers Bureau; Abbive: Current equity holder in publicly-traded company; Baxter: Current equity holder in publicly-traded company; Takeda: Current equity holder in publicly-traded company; Alexion: Consultancy, Research Funding, Speakers Bureau.

Introduction The improvement of care and advancement of treatment options is heavily reliant on the success and diversity of clinical trials (CTs), yet data suggests that only 3-9% of patients with a cancer diagnosis participate in CTs. We sought to evaluate reasons for declining participation in CTs among patients with hematologic malignancies within our medical center. Our primary objective was to assess the prevalence of non-clinical factors in patients contributing to the lack of participation compared to those who agreed to participate. The secondary objective was to identify the reasons noted by patients for declining trials. Methods We conducted a retrospective chart review of adult patients with hematologic malignancies who were offered a clinical trial from 2016-2020. Eligible patients were identified through review of Cancer Center Clinical Trials Office screening logs. We collected data relative to: disease, sex, age, race and ethnicity, English as a first language, marital status, caregiver support, level of education, type of insurance, trial phase, and trial indication. The data was compared between patients who refused participation versus those who agreed to participate. Descriptive statistics, chi-square analysis, and multivariate logistic regression were used to interpret the data with IBM SPSS Statistics. Results Of patients diagnosed with hematologic malignancies and offered a CT from 2016 to 2020 at our center, 136 signed consent and 125 declined participation. The sample was predominantly older with a mean patient age of 60.9 in those who signed ICF and 61.9 in those who declined participation (Table 1). Males and non-Hispanic white patients encompassed over half of the sample in each group. Multiple myeloma was the most common diagnosis among either group. Trials offered were predominantly phase 2 or 3 and for varying disease states. We found that patients who were divorced (P = 0.024), did not have caregiver support (P = 0.005), and did not speak English as their first language (P = 0.004) were more likely to decline CT participation (Table 2). The most common reasons that patients cited for declining participation were: preference for another treatment option, distance for travel, and concerns for transportation (Table 3). Conclusion In this retrospective analysis evaluating reasons behind CT refusal in patients with hematologic malignancies at our center, we found that being divorced, not having defined caregiver support, and not speaking English as the first language made patients more likely to decline a CT. Our sample displayed greater diversity in comparison to the national averages for cancer CT participation despite the predominance of male and non-Hispanic white patients within our sample. This may be representative of the population our center serves. The significance of marital status and caregiver support suggests that support systems are integral in the decision-making process for CTs. Furthermore, the role of divorce in declining trials may be indicative of familial motivation or spousal influence. The significance of English as a first language is notable as our center utilizes an oral translation for informed consent with a short form signature. This suggests that a full translation of CT documents may be beneficial to enrollment. Logistical concerns were frequently cited as a reason for declining, which should be considered by sponsors in the design of CTs as alleviating this burden on patients may help overall recruitment. Limitations of this study include its retrospective nature, manual data extraction, and consistency of research team documentation. The results suggest that introducing support groups and interventions to provide transportation services for trial patients may be beneficial to enrollment and retention. Figure 1 Figure 1. Disclosures Shammo: Abbvie: Current holder of individual stocks in a privately-held company, Research Funding; Astra zeneca: Research Funding; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; Incyte: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Apellis: Consultancy, Membership on an entity's Board of Directors or advisory committees; CTI pharma: Research Funding; Stemline therapeutics: Research Funding; Kartos Pharma: Research Funding; Alexion: Consultancy, Honoraria, Research Funding, Speakers Bureau; sanofi: Consultancy, Honoraria, Speakers Bureau; Baxter: Current holder of stock options in a privately-held company; Takeda: Consultancy, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Honoraria, Research Funding; NS Pharma: Membership on an entity's Board of Directors or advisory committees. Paner: Adaptive Biotechnologies: Consultancy; Amgen: Consultancy; GSK: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Oncopeptides: Consultancy; Rush University Medical Center: Consultancy, Current Employment; Sanofi: Consultancy; BMS: Consultancy. Ustun: novartis: Honoraria; Blueprint: Honoraria.

Inflammatory breast cancer (IBC) is a rare but aggressive form of breast cancer with unique clinicopathological features and poor prognosis. Its epidemiology is distinct from noninflammatory locally advanced breast cancer (LABC), which points to different etiology. With the advent of multimodality treatment for LABC, the outcomes for women with IBC have improved, but remain significantly inferior to outcomes for noninflammatory LABC. This review focuses on new research in epidemiology and molecular pathways characteristic for IBC. One of the critical carcinogenic events apparently driving the development and progression of IBC is activation of the RhoC protein, which is a part of the Ras oncogene superfamily. These proteins, like other Ras proteins, require posttranslational prenylation for their activation and transfer to cell membranes. Farnesylation is a common type of prenlyation that can be blocked with a new class of drugs - farnesyltransferase inhibitors. The most advanced farnesyltransferase inhibitor in development, tipifarnib, has been evaluated in Phase II clinical trials as monotherapy and in combination with antihormonal agents and trastuzumab in metastatic and locally advanced breast cancer. A few tumor responses have been observed in these trials, but not enough to warrant a Phase III trial. Potential combinations of tipifarnib with other novel agents targeting enzymes downstream to RhoC are reviewed. Some of these drugs, such as imatinib and crizotinib, are already commercially available. Others like perifosine and anti-vascular endothelial growth factor 3 antibody are currently under development. Innovative trial designs to address this rare type of cancer are discussed.

572 Background: This analysis was prompted by a patient who presented with SBBC who had and ER+, HER2- cancer in one breast and an ER-, HER2+ cancer in the other. Since both breasts have the same genetic background and environmental exposures, concordance should be virtually identical unless other factors are at play. Methods: SBBC was defined as bilateral cancer diagnosed concurrently or within 6 months of each other. Cases were identified retrospectively from patients seen at Rush University Medical Center. This analysis was limited to invasive SBCC (ISBBC). Estrogen receptor (ER) and Her2/neu (HER2) status were assessed according current ASCO/CAP guidelines. Correlation between ER and HER2 status was determined using κ statistic. Results: From January 1998 to December 2012, 33 cases of ISBBC were diagnosed. In 65% of cases synchronous disease was diagnosed concurrently. The average age at diagnosis was 56. The majority were multiparous and 79% post menopausal. About half of the patients (55%) had at least one first degree relative with a history of breast or ovarian cancer and 9% of the cohort had a deleterious mutation in BRCA1 or BRCA2. Infiltrating ductal was most common (74%) followed by infiltrating lobular (21%). 53% of breasts specimens also contained ductal carcinoma in situ. 68% of tumors were ER positive and 8% were HER2 positive. Concordance in ER status was seen in 73% of cases (kappa coefficient 0.14) and in HER2 status was 64% (Kappa coefficient 0.35). Conclusions: Despite identical hereditary and environmental exposure, some patients develop ISBBC cancers with discordant receptor status. While this is the exception, it suggests that other factors influence important tumor characteristics. [Table: see text]

Abstract 4918 Background: Improved outcomes have been demonstrated in DLBCL with dose dense CHOP (CHOP-14), the addition of immunotherapy to CHOP, and radioimmunotherapy consolidation following CHOP chemotherapy. A prospective, single-arm, open-label, nonrandomized phase II trial was conducted using a combination of the above with dose dense CHOP+R, every 2 weeks, followed by radioimmunotherapy consolidation to evaluate its efficacy and safety in untreated DLBCL patients. Patients and Methods: 20 eligible patients (measurable disease, age >18 years, performance status 0–2, adequate marrow, liver and kidney function) with previously untreated DLBCL were enrolled. Patients with transformed lymphoma were excluded. Patients received standard CHOP along with rituximab 375mg/m2 IV on day 1, every two weeks for 6 cycles, followed by Zevalin 6–8 weeks later. Efficacy of Study: In 20 treated patients, ORR was 100% with 90% CR and 10% PR. 16 patients received the entire treatment regimen as intended. 3 patients (15%) relapsed. All relapses were retreated with one patient now in CR and 2 deceased. One other patient, who did not receive Zevalin, is also deceased from organizing pneumonia 2 years after last chemotherapy. Safety Results: The most common adverse effects of this regimen were hematological. All patients (n=20) had anemia during CHOP+R pre-Zevalin, 15 (75%) patients with grade 1/2 and 5 (25%) with grade 3 anemia. 11 patients had thrombocytopenia, 4 with grade 3/4 toxicity. Neutropenia was present during CHOP+R therapy in 14 patients (70%), 2 cases of grade 2 and 12 cases of grade 4 toxicity. However, neutropenic fever only occurred in 4 patients, all with grade 1/2 neutropenia. Neuropathy was also a common toxicity (15 patients), with grade 3 toxicity occurring in 4 patients. Less common adverse effects, all ≤ grade 2, included anorexia, constipation, nephrolithiasis, diarrhea, urinary frequency, dysgeusia and rhinitis. With completion of dose dense chemotherapy, one patient had organizing pneumonia, one had grade 2 pneumonitis, and one had bronchiectasis, all precluding the use of Zevalin. Pre and post chemotherapy MUGA scans demonstrated stable left ventricular ejection fractions in all but one patient, who remains in CR. Zevalin was completed by 16 patients (80%). Zevalin induced grade 3/4 cytopenias occurred in 8 patients (50%), the most common being neutropenia (all 8 patients) with no cases of neutropenic fever. 12 (75%) patients experienced thrombocytopenia, though only 2 had grade 3/4 effects. Grade 3 syncope occurred in one patient. All other non-hematologic effects were ≤ grade 2 and included neuropathy, sinus and yeast infections, folliculitis, rash, diarrhea, nausea, and urinary incontinence. Conclusion: Consolidation with Zevalin radioimmunotherapy following dose dense CHOP+R therapy is well tolerated, safe and non-life threatening among our sample population of untreated DLBCL. Disclosures: Off Label Use: Chemotherapy with R-CHOP every 21 days is the standard of care for DLBCL in the front-line setting. We are administering R-CHOP every 14 days for dose intensification followed by zevalin (radioimmunotherapy) consolidation for untreated DLBCL. This regimen is off-label. Gregory: Amgen: Consultancy; Astellas: Research Funding; Celgene: Research Funding; Cephalon: Research Funding, Speakers Bureau; Genentech (Roche): Consultancy, Research Funding, Speakers Bureau; Glaxo-Smith-Kline: Research Funding; Immunomedics: Research Funding; NCIC CTG: Research Funding; Novartis: Consultancy, Research Funding; Onyx (Proteolix): Research Funding; Spectrum Pharmaceuticals: Consultancy.

Background: The Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders, characterized by cytopenia, and risk of progression to acute leukemia. Chromosomal abnormalities are detected in 40–60%of patients with MDS. Cytogenetic findings are critical for diagnosis, prognosis and monitoring therapy. FISH has been reported to detect occult clonal abnormalities in 15–7.8% of karotypically normal patients in some studies, but found to be of limited value in others. We sought to evaluate whether FISH can be a valuable diagnostic/prognostic adjunct to conventional cytogenetic (CC) analysis. Methods: Since the implementation of FISH panel at our institution, we have identified 62 MDS patients who had both CC and FISH panel tests performed simultaneously. Our FISH panel was designed specifically to detect abnormalities in chromosomes 5, 7, 8, 11 and 20. Results: In these patients, concordance between the 2 methods was noted in 43 patients (69.3%). Clonal chromosomal abnormalities were detected by CC in 36 patients (58 %). FISH defined additional clones in 7/26 patients with normal and 3/36 patients with an abnormal karyotype increasing the detection rate by 16%. Importantly, 9/36 patients with abnormal CC had clonal abnormalities in chromosome regions not analyzed, thus not detected, by our FISH panel. To further evaluate the prognostic significance of the additional clones detected by FISH, we calculated and compared the IPSS risk category for the 10 patients identified with discordant results utilizing data derived from CC and FISH. 3 patients had no change in their IPSS scores, 7 patients had an upgrade in their IPSS scores as follows: from low to Int-1: 4, Int-1 to Int-2: 2, and Int-2 to High: 1. If one were to apply NCCN guidelines with regard to treatment options according to IPSS risk categories, FISH upgraded scores could potentially result in change of therapy in 2/10 patients with discrepancy, and in 2/62 (3%) patients altogether. Conclusion: Our results suggest that FISH has the potential of increasing the rate of detecting chromosomal abnormalities in complete CC studies that have failed to reveal clonal abnormalities. However, the practical impact of finding such clones seems to be very low resulting in potential change of clinical management in only 3% of patients. Furthermore, in cases with identified cytogenetic abnormalities, FISH was of limited benefit. Our series is small and retrospective in nature; prospective studies addressing the utility, benefit, and cost justification of this method are needed.

4918 Background: Improved outcomes have been demonstrated in DLBCL with dose dense CHOP (CHOP-14), the addition of immunotherapy to CHOP, and radioimmunotherapy consolidation following CHOP chemotherapy. A prospective, single-arm, open-label, nonrandomized phase II trial was conducted using a combination of the above with dose dense CHOP+R, every 2 weeks, followed by radioimmunotherapy consolidation to evaluate its efficacy and safety in untreated DLBCL patients. Patients and Methods: 20 eligible patients (measurable disease, age >18 years, performance status 0–2, adequate marrow, liver and kidney function) with previously untreated DLBCL were enrolled. Patients with transformed lymphoma were excluded. Patients received standard CHOP along with rituximab 375mg/m2 IV on day 1, every two weeks for 6 cycles, followed by Zevalin 6–8 weeks later. Efficacy of Study: In 20 treated patients, ORR was 100% with 90% CR and 10% PR. 16 patients received the entire treatment regimen as intended. 3 patients (15%) relapsed. All relapses were retreated with one patient now in CR and 2 deceased. One other patient, who did not receive Zevalin, is also deceased from organizing pneumonia 2 years after last chemotherapy. Safety Results: The most common adverse effects of this regimen were hematological. All patients (n=20) had anemia during CHOP+R pre-Zevalin, 15 (75%) patients with grade 1/2 and 5 (25%) with grade 3 anemia. 11 patients had thrombocytopenia, 4 with grade 3/4 toxicity. Neutropenia was present during CHOP+R therapy in 14 patients (70%), 2 cases of grade 2 and 12 cases of grade 4 toxicity. However, neutropenic fever only occurred in 4 patients, all with grade 1/2 neutropenia. Neuropathy was also a common toxicity (15 patients), with grade 3 toxicity occurring in 4 patients. Less common adverse effects, all ≤ grade 2, included anorexia, constipation, nephrolithiasis, diarrhea, urinary frequency, dysgeusia and rhinitis. With completion of dose dense chemotherapy, one patient had organizing pneumonia, one had grade 2 pneumonitis, and one had bronchiectasis, all precluding the use of Zevalin. Pre and post chemotherapy MUGA scans demonstrated stable left ventricular ejection fractions in all but one patient, who remains in CR. Zevalin was completed by 16 patients (80%). Zevalin induced grade 3/4 cytopenias occurred in 8 patients (50%), the most common being neutropenia (all 8 patients) with no cases of neutropenic fever. 12 (75%) patients experienced thrombocytopenia, though only 2 had grade 3/4 effects. Grade 3 syncope occurred in one patient. All other non-hematologic effects were ≤ grade 2 and included neuropathy, sinus and yeast infections, folliculitis, rash, diarrhea, nausea, and urinary incontinence. Conclusion: Consolidation with Zevalin radioimmunotherapy following dose dense CHOP+R therapy is well tolerated, safe and non-life threatening among our sample population of untreated DLBCL. Disclosures: Off Label Use: Chemotherapy with R-CHOP every 21 days is the standard of care for DLBCL in the front-line setting. We are administering R-CHOP every 14 days for dose intensification followed by zevalin (radioimmunotherapy) consolidation for untreated DLBCL. This regimen is off-label. Gregory: Amgen: Consultancy; Astellas: Research Funding; Celgene: Research Funding; Cephalon: Research Funding, Speakers Bureau; Genentech (Roche): Consultancy, Research Funding, Speakers Bureau; Glaxo-Smith-Kline: Research Funding; Immunomedics: Research Funding; NCIC CTG: Research Funding; Novartis: Consultancy, Research Funding; Onyx (Proteolix): Research Funding; Spectrum Pharmaceuticals: Consultancy.