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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 - Data regarding efficacy and toxicity of different bridging strategies prior to CAR-T therapy are scanty. Tisagenlecleucel (Kymriah TM, Novartis) and axictagene ciloleucel (Yescarta TM, Kite/Gilead) were commercially approved for relapsed/refractory (R/R) DLBCL since 2019. We analyzed real-life data of CAR-T therapy among all consecutive patients who were treated in 4 different CAR-T centers in Israel. Methods - From May 2019, 144 R/R DLBCL patients underwent apheresis and continued to receive bridging therapy that included chemo/immunotherapy (n=78, 54%), radiation (n=11, 7.6%), chemoradiation (n=22, 15%), steroids only (n=5, 3.5%) and none (n=28, 19.4%). All patients were evaluated after bridging therapy and prior to CAR-T infusion by PETCT (96%) or CT scan (4%). Results - Median age was 68 (20-88) years and Median follow-up was 13 (4-26) months. All 144 patients underwent successful apheresis. Reasoning for choosing specific bridging therapy was based on low tumor mass (n= 23, 16%), high tumor mass (n=73, 51%), frailty of the patient (n=27, 19%), ongoing significant prior regimen's toxicities (n=14, 10%) and local disease (n=7, 4%). In patients given radiation therapy median dose was 23 (range, 8-30) Gy. In patients given chemo/immunotherapy or chemoradiation, sepsis was the main complications (9% of all patients) during bridging therapy. However, none of the patients had a fatal event. 14 patients (9.7%) did not proceed to CAR-T infusion; 6 (4.2%) had disease progression and died; 8 (5.6%) had manufacture failure). Among the 130 patients that received CAR-T infusion, PET-CT prior to preparative regimen demonstrated CR/PR status in 38%, 50%, 40%, 17%, and 16% of patients given chemotherapy, radiation, chemoradiation, steroids only, or no bridging therapy, respectively (p=.15), Figure 1. Any bridging therapy was associated with a better disease control compared to either steroids only or no treatment (p=.012). There were no differences in the incidences of overall CRS (p=.692), grade 3-4 CRS (p=.196), overall ICANS (p=.941), grade 3-4 ICANS (p=.281), acute kidney disease (p=.244), and liver dysfunction (p=.45) between the 5 different bridging strategies. Cardiovascular complications were more common after chemoradiation (36%), chemotherapy (19%) and radiation (13%), compared with steroids (0%) or no bridging therapy (4%), p=.05. Non-relapse mortality was 0 in all subgroups. PETCT at 1-month post CAR-T infusion demonstrated an increase in CR status percentage across all subgroups with no statistically significant difference in the incidence between the subgroups (p=.27), Figure 1. There was no difference in both progression-free survival (Figure 2) and overall survival between the 5 subgroups (p=.7, and p=.23). Cox regression model identified preinfusion lower ECOG status (HR=0.8, p=.04), preinfusion CR/PR status (HR=.46, p=.037) and 1-month post infusion CR status as a time dependent co-variate (HR=.14, p Conclusions - Bridging to CAR-T should be tailored based on patient's and disease's characteristics with the aim to achieve the best disease control prior to CAR-T. However the chosen strategy per-se does not impact long-term outcomes. Intensive bridging therapy is associated with more cardiovascular events after CAR-T infusion. A prospective-controlled-trial allocating patients to different bridging strategies is needed to verify these results. Figure 1 Figure 1. Disclosures Ram: Gilead: Honoraria; Novartis: Honoraria. Yehudai-Ofir: Novartis: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees. Avivi: Novartis: Speakers Bureau; Kite, a Gilead Company: Speakers Bureau. Zuckerman: Cellect Biotechnology: Honoraria; Gilead Sciences: Honoraria, Speakers Bureau; Novartis: Honoraria; Janssen: Honoraria; BioSight Ltd: Honoraria; Orgenesis Inc.: Honoraria; AbbVie: Honoraria. Yeshurun: Astellas: Consultancy; Janssen: Consultancy. Gurion: Medison; Gilead Sciences; Takeda Pharmaceuticals: Consultancy; JC Health CARE; Roche: Honoraria. Levi: AbbVie: Consultancy, Research Funding.

Background: Intra-articular bleeding (hemarthrosis) accounts for 80-90% (Roosendaal, et. al. Semin Thromb Hemost . 2003;29:37) of all bleeds and more than 90% of serious bleeding events in patients with severe hemophilia (Valentino. J Thromb Haemost . 2010;8:1895). Recurrent hemarthroses result in progressive joint damage and the development of hemophilic arthropathy (HA) in up to 50% of adults with hemophilia (Forsyth, et al. Haemophilia . 2014;20:44). Acetaminophen is commonly prescribed for pain due to HA yet has limited efficacy at therapeutic doses (Rodriguez-Merchan. Blood Rev. 2018;32:116). Traditional non-steroidal anti-inflammatory drugs (tNSAIDs) inhibit platelet function and cause gastrointestinal (GI) complications including bleeding, both of which can be harmful in patients with hemophilia (Rodriguez-Merchan. Blood Rev. 2018;32:116; Brooks, et al. Rheumatology . 1999;38(8):779). Opioids are prescribed in over 60% of patients with HA(Witkop, et al. Haemophilia. 2012;18:e115) despite dependence, potential for abuse, and an increased risk of falls and other opioid-related injury (Rodriguez-Merchan. Blood Rev. 2018;32:116). Given an unmet need in pain management for HA, alternate approaches are needed. TRM-201 (rofecoxib) is a cyclooxygenase-2 (COX-2) selective NSAID with no impact on platelet function and a lower GI risk than tNSAIDs (Vioxx (rofecoxib) package insert. Merck & Co. I, ed. Whitehouse Station, NJ, 2004). The RESET-HA study is designed to evaluate the efficacy and safety of rofecoxib for HA pain management. Methods/Design: RESET-HA is a multi-national, randomized, double-blind study to evaluate the efficacy and safety of rofecoxib in hemophilia A or B patients with diagnosed HA, aged 12 to 75 years and is based on a previous pilot study (Tsoukas, et al. Blood, 2006;107:1785). Patients must have a history of joint bleeding, and chronic symptomatic pain in one or more joint(s) on 20 of the 30 days prior to screening. Exclusion criteria include use of opioids for greater than 4 days/week, or opioid transdermal patches in the 30 days prior to screening, history of GI perforation, ulcer or bleeding, peptic ulcer disease and major cardiac ischemic symptoms or events. Randomized patients (n=80 per arm) are washed out of analgesics prior to daily administration of TRM-201 (17.5 mg/day) or placebo for 12 weeks (Part I) during which acetaminophen (Stage-1) and acetaminophen plus codeine (Stage-2) are available as rescue medication (where available and acceptable to the patient and study doctor). The patient assessment of hemophilic arthropathy pain, a 0- to 10-point numeric rating scale validated for the assessment of pain across many disease states, is recorded daily. The primary endpoint is the placebo adjusted change from baseline in weekly average of patient assessment of daily HA pain score at Week 12. Key secondary endpoints include patient assessments using the PROMIS physical function instrument and pain interference from the Brief Pain Inventory. Sleep disturbance is also measured using the PROMIS instrument. The study explores the efficacy of rofecoxib on the number of suspected joint bleeds and on the amount of rescue medication used. Following Part I, all study patients (regardless of original randomization arm) receive rofecoxib 17.5 mg once daily for up to 12 additional months (Part II). During Part II of the study, only acetaminophen will be provided as rescue medication. Discussion: The RESET-HA study is intended to evaluate the efficacy and safety of TRM-201 in patients with HA and is the first Phase III trial ever conducted to assess a treatment for HA pain. Pain management in HA requires analgesic anti-inflammatory treatment that does not exacerbate bleeding. Rofecoxib has been shown to have no effect on platelet function, even at supratherapeutic doses(Vioxx (rofecoxib) package insert. Merck & Co. Whitehouse Station, NJ, 2004), a decreased risk of GI side effects, including GI bleeding compared with tNSAIDs, and no greater cardiovascular risk than equipotent doses of COX-2 selective and tNSAIDs (U.S. Food and Drug Administration. J Pain Palliat Care Pharmacother. 2005;19:83). TRM-201 is anticipated to provide analgesic efficacy, with an acceptable tolerability and safety profile, and could become a new treatment option that may possibly facilitate the avoidance of opioid use in patients with HA. (NCT04684511) Disclosures Boice: Tremeau Pharmaceuticals Inc.: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Buckner: Novo Nordisk: Honoraria; American Thrombosis: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Honoraria; Genetech: Honoraria; Spark: Honoraria; Sanofi: Honoraria; Bayer: Honoraria; Pfizer: Honoraria; Takeda: Honoraria; Tremeau Pharmaceuticals: Consultancy, Honoraria; uniQure: Consultancy, Honoraria; BioMarin: Consultancy, Honoraria; Hemostasis Network: Membership on an entity's Board of Directors or advisory committees. Croteau: Tremeau Pharmaceuticals,Inc: Consultancy. Katz: Tremeau Pharmaceuticals,Inc: Consultancy. Sidonio: Takeda: Consultancy, Research Funding; Octapharma: Consultancy, Research Funding; Catalyst: Consultancy; Guardian Therapeutics: Consultancy; Bayer: Consultancy; Novo Nordisk: Consultancy; Biomarin: Consultancy; Pfizer: Consultancy; Genentech: Consultancy, Research Funding. Bolognese: Tremeau Pharmaceuticals,Inc: Consultancy. Garfield: Tremeau Pharmaceuticals,Inc: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Corrigon: Tremeau Pharmaceuticals,Inc: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Walsh: Genentech: Consultancy; Biomarin: Consultancy; Takeda: Consultancy; Novo Nordisk: Consultancy; Tremeau: Consultancy.

Introduction - primary refractory AML is associated with a dismal prognosis. Only 30% of patients will respond to salvage chemotherapy and continue to allogeneic hematopoietic cell transplantation (HCT) with a 10-20% long- term overall survival. Following from the FLAMSA protocol, we implemented a modified RIC regimen - FITCy (fludarabine, cytarabine +/- idarubicin and 4 Gy TBI) in all primary refractory patients with a donor available for transplant. Methods - all patients who were admitted with AML, were identified by the transplantation coordinator nurse and underwent donor evaluation within 2 days from diagnosis. Patients who received induction chemotherapy had a day 14 marrow examination and where leukaemia blasts were identified, donor search was prioritized. These patients went on to have a day 28 bone marrow examination to confirm refractory disease. Patients who were treated with azacitidine ±venetoclax had a 2-month BM evaluation and donor search was prioritized in case of refractory disease. All consecutive patients, diagnosed with primary refractory AML, underwent HCT with the FITCy regimen in the Tel Aviv Sourasky Medical Center. Patients who underwent sequential therapy for relapsed disease (either chemosensitive or refractory) or a second HCT were excluded from this analysis. The protocol was amended on January 2018 to include ATG for all patients after interim analysis showed a high rate of GVHD. Results - Between January 2014 and June 2021, 48 patients were identified with primary refractory disease and were eligible for the protocol. Median age was 63 (range, 22-75) years (Table). Median follow-up for surviving patients was 33 (range, 1-81) months. Prior to HCT, 12 (25%) patients had ongoing documented infections (either microbiology or clinically). Median days to engraftment of neutrophils (>500/dL) and to complete engraftment of platelets (>20000/dL) were 10 (range, 7-20) days, and 16 (9-35) days, respectively. 7 patients with early progression/non relapse mortality were not evaluated for this outcome. No patient had primary/secondary graft rejection. Severe mucositis was observed in only 7 patients (15%) and was mostly observed in the upper gut. 18 patients (38%) developed microbiology documented infections during the neutropenic period and in 7 (40%) this directly contributed to mortality. Only 2 patients (4%) developed sinusoidal obstruction syndrome. Complete remission was documented on day 30, in all but 1 patient with a median whole marrow donor chimerism of 98% (range, 73-100%).Cumulative incidences of grade 2-4 and 3-4 acute GVHD at day 100 were 55% and 15%, respectively. Cumulative incidences of overall chronic GVHD and moderate-severe chronic GVHD at 1 year after HCT were 64% and 24%, respectively. Cumulative incidences of relapse at 1 year and 2 years post HCT were 24% and 30%, respectively. Non-relapse mortality rates, at 30 days, 100 days and 1 year post HCT were 13%, 20%, and 32%, respectively. Cumulative incidences of 1, 2, and 3 years overall survival were 50%, 42%, and 42%, Figure. Cox regression analysis for overall survival identified increased time from diagnosis (HR-1.03, p=.046), mismatched donor (HR-1.4, p=.05) and the use of ATG (HR=.33, p=.006) to impact survival, while age, sex and comorbidity index were not predictive. Conclusions - Sequential therapy in patients with primary refractory AML provides a remarkable anti- leukemic effect. A timely donor search program is essential for the succession of this approach. Nevertheless, infection control and GVHD prophylaxis is still suboptimal and future protocols should focus on these domains while preserving graft vs. leukemia function. Figure 1 Figure 1. Disclosures Moshe: AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Astellas: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Lectures. Avivi: Novartis: Speakers Bureau; Kite, a Gilead Company: Speakers Bureau. Ram: Novartis: Honoraria; Gilead: Honoraria. OffLabel Disclosure: Off label Cellcepet for prophylaxis of GVHD

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.

Introduction: CC-92480 is a potent, novel CELMoD ® compound designed for rapid and maximal degradation of Ikaros and Aiolos, that has shown immunostimulatory effects and enhanced tumoricidal activity in myeloma cells, including those resistant to lenalidomide (LEN) and pomalidomide (POM). CC-92480 has demonstrated potent synergy with DEX, proteasome inhibitors (PIs), and anti-CD38 monoclonal antibodies (mAbs) (Wong L, et al. Blood 2019;134[suppl 1]:1815). In pts with RRMM, CC-92480 in combination with DEX demonstrated a manageable safety profile with promising preliminary efficacy (Richardson PG, et al. J Clin Oncol 2020;38[suppl 15]:8500). CC-92480-MM-002 (NCT03989414) is an ongoing phase 1/2 study evaluating CC-92480 in combination with standard treatments in pts with RRMM. Here we report preliminary results from the CC-92480 + BORT + DEX cohort. Methods: Pts with RRMM who had received 2-4 prior regimens, including prior treatment with LEN, and had documented disease progression during or after their last myeloma therapy were eligible. CC-92480, at specified cohort doses (0.3 mg, 0.6 mg, and 1.0 mg), was administered orally on days (D) 1-14 with subcutaneous BORT (1.3 mg/m 2) on D1, 4, 8, and 11 in cycles (C) 1-8 and on D1 and 8 after C8, over a 21-day cycle; DEX (20 mg/day or 10 mg/day if > 75 years of age) was given on D1, 2, 4, 5, 8, 9, 11, and 12 in C1-8 and on D1, 2, 8, and 9 after C8. Primary objectives were to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), and to evaluate safety and preliminary efficacy. Pharmacodynamics (PD), Ikaros/Aiolos protein levels, and immunophenotyping were also assessed. Results: As of May 26, 2021, 19 pts had received CC-92480 + BORT + DEX. Median age was 66 (50-83) years, median time since initial diagnosis was 4.8 (1.9-17.1) years, and median number of prior regimens was 3 (2-4). Prior therapies included stem cell transplantation (57.9%), BORT (78.9%), carfilzomib (CFZ, 21.1%), LEN (100%), POM (47.4%), and anti-CD38 mAbs (36.8%); 21.1% of the pts had extramedullary disease and 21.1% were triple-class refractory (refractory to immunomodulatory drug, PI, and anti-CD38 mAb). Median follow-up was 8 (1.0-19.2) months, with a median number of 10 (1-28) cycles received and 9 (47.4%) pts continue on treatment. Main reason for discontinuation was progressive disease, reported in 5 pts. All pts experienced ≥ 1 treatment-emergent adverse events (TEAEs) and grade (Gr) 3-4 TEAEs were reported in 18 (94.7%) pts. Most frequent (≥ 10% of pts) Gr 3-4 TEAEs were neutropenia (36.8%, no febrile neutropenia reported), thrombocytopenia (21.1%, no bleeding reported), anemia (10.5%), hyperglycemia (10.5%), and insomnia (10.5%). Gr 3-4 infection was reported in 1 (5.3%) pt. Eight (42.1%) pts had Gr 1-2 peripheral neuropathy. Five (26.3%) pts had serious TEAEs, none considered related to study treatment. Five (26.3%), 7 (36.8%), and 8 (42.1%) pts had dose reductions of CC-92480, BORT, and DEX, respectively; 4 (21.1%) pts had dose reductions due to TEAEs. Two (10.5%) pts discontinued due to TEAEs (dysgeusia and colon neoplasm [pre-existing]). No pt experienced dose-limiting toxicity and the MTD was not reached. Two deaths were reported (due to myeloma progression and colon neoplasm). The overall response rate across all doses per investigator assessment was 73.7% (14/19 pts), including 3 stringent complete responses and 1 complete response. Responses were observed at all dose levels. Median duration of response was 10.4 (5.5-not reached) months and median time to first response was 0.95 (0.7-3.3) months. Plasma exposures of CC-92480 + BORT + DEX were consistent with previous pharmacokinetic (PK) analysis of CC-92480 + DEX. Consistent with CC-92480 mechanism of action, PD studies showed potent degradation of substrates 3-6 hours post treatment and a reduction of mature B cells with CC-92480 + BORT + DEX treatment. Based on safety, efficacy, and PK/PD data, a 1.0 mg dose of CC-92480 was selected as the RP2D. Conclusions: CC-92480 in combination with BORT and DEX appears to be safe and well tolerated with encouraging preliminary efficacy in pts with RRMM. These results support further development of CC-92480 in combination regimens in RRMM. In the CC-92480-MM-002 study, a CC-92480 + BORT + DEX expansion cohort is ongoing at the RP2D, as well as a CC-92480 + CFZ + DEX cohort. Updated data will be presented at the meeting. Disclosures Richardson: Secura Bio: Consultancy; GlaxoSmithKline: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy; AstraZeneca: Consultancy; Regeneron: Consultancy; Sanofi: Consultancy; Oncopeptides: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Protocol Intelligence: Consultancy; AbbVie: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding. Ocio: Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Amgen: Consultancy, Honoraria; Bristol-Myers Squibb/Celgene: Consultancy, Honoraria; Karyopharm: Consultancy; MSD: Honoraria; Oncopeptides: Consultancy, Honoraria; Pfizer: Consultancy; Secura-Bio: Consultancy. Raje: Caribou: Other; Janssen: Other; bluebird bio: Other; Amgen: Other; Celgene: Other; BMS: Other. White: Amgen: Consultancy, Honoraria; Antengene: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Forus: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Oriol: Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Sandhu: Celgene/BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Raab: Sanofi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees. LeBlanc: Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Sanofi Canada: Membership on an entity's Board of Directors or advisory committees; Janssen Canada: Membership on an entity's Board of Directors or advisory committees; BMS/Celgene Canada: Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Research Funding; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. Rodriguez: BMS: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Oncopeptides: Consultancy, Honoraria; Amgen: Consultancy, Speakers Bureau; Karyopharm: Consultancy, Speakers Bureau. Trudel: Sanofi: Honoraria; Roche: Consultancy; GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Genentech: Research Funding; BMS/Celgene: Consultancy, Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria, Research Funding. Wäsch: Pfizer: Consultancy; Amgen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Novartis: Consultancy; BMS/Celgene: Consultancy; Gilead: Consultancy. Perrot: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Honoraria. Bahlis: BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Genentech: Consultancy; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Zhou: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Lamba: Bristol Myers Squibb: Current Employment; Pfizer: Current equity holder in publicly-traded company. Amatangelo: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Civardi: Bristol Myers Squibb: Current Employment. Katz: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Maciag: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Peluso: Celgene, a Bristol-Myers Squibb Company: Current Employment. Dimopoulos: BMS: Honoraria; Janssen: Honoraria; Beigene: Honoraria; Takeda: Honoraria; Amgen: Honoraria.

Background: Pomalidomide (POM) is an established agent in relapsed/refractory (R/R) multiple myeloma (MM) with direct cytotoxicity against MM cells and immunostimulatory activities in multiple cell types including T cells and NK cells. CC-92480 is a novel Aiolos/Ikaros degrading cereblon E3 ligase modulator (CELMoD ®) agent is currently being investigated in combination with the proteasome inhibitor (PI) bortezomib (BTZ) and corticosteroid dexamethasone (DEX), or with DEX only in R/R MM (CC-92480-MM-002 and CC-92480-MM-001). Previous results indicate that triplet combination of POM/BTZ/DEX may enhance some T, B and NK cell subpopulations, overcoming immunosuppression when compared to BTZ/DEX-only treated patients (Rao et al, 2019). Mechanisms of action (MOA) of CC-92480- and POM-mediated substrate depletion occurs via ubiquitination and proteasome degradation, where BTZ has been speculated as potentially antagonistic as a PI. Here, we report pre-clinical and clinical observations of an immune MOA of CC-92480 or POM in combination with BTZ. Results: To mimic the clinical pharmacokinetics, BTZ was utilized as a high-dose pulse method alone and in combination with POM or CC-92480, followed by flow cytometric measurements of Aiolos and Ikaros protein abundance in healthy donor (HD) T cells. The addition of BTZ modestly delayed CRBN-dependent substrate depletion compared to single agent POM or CC-92480; however, this effect was only apparent at early time points (1-6 hr) where the effect was negligible by 24 hr. To understand the functional implications of BTZ combination, we conducted CD3-stimulated PBMC-mediated cytotoxicity assay against H929 MM target cells in a co-culture model. The efficiency of POM or CC-92480 induced PBMC-mediated killing in a dose dependent manner (~65% increase compared to DMSO) were similar at a 100-fold lower dose range of CC-92480 compared to POM, with the effect not being altered by co-treatment with BTZ. These data were replicated with a POM or CC-92480 treated supernatant stimulation of purified NK cells co-culture, which induced an 80% reduction in target cell viability with the BTZ combination having no negative effects on CELMoD-mediated activity. Cytokine analysis on PBMC supernatants treated with either POM or CC-92480 in the absence or presence of BTZ-pulse showed a dose-dependent increase in IL-2 (>2.4-fold) and Granzyme B (>3.1-fold), which were not impacted by BTZ co-treatment. As a secondary readout on activation status, we measured multiple signaling molecules and activation markers on the cell surface of T and NK cell subsets in CD3 stimulated HD PBMCs treated with dose-dependent POM or CC-92480 with or without co-treatment of BTZ. Compared to DMSO controls, elevated expression levels of CD25 (IL2RA), CD278 (ICOS), Granzyme B, CD134 (OX40R) and HLA-DR were observed with both POM and CC-92480 on CD4, CD8 and NK cells demonstrating a CELMoD-mediated increase in immune activation. These effects were not impacted by the co-treatment of BTZ. Examination of peripheral blood samples from MM patients enrolled in the CC-92480-MM-001/002 (NCT03374085/NCT03989414) clinical trials revealed that CC-92480 promoted potent immunomodulation when administered in combination with DEX and with BTZ/DEX. These data included increased numbers of activated and central memory T cells, as well as increased Ki67+ proliferating T and NK cell populations compared to samples collected during the screening period before any drugs had been administered, consistent with earlier observation of POM in combination with BTZ/DEX treated patients. Conclusions: Taken together, these data demonstrate that POM and CC-92480 are potent immunomodulatory agents with enhanced induction of PBMC and NK mediated cell killing of MM tumor cells and activation of T and NK cells, at 100-fold lower concentrations of CC-92480 compared to POM. Additionally, we showed that combination with BTZ in preclinical assays and in the clinical setting did not antagonistically affect the immunostimulatory ability of POM or CC-92480. Disclosures Bjorklund: BMS: Current Employment, Current equity holder in publicly-traded company. Amatangelo: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Chiu: Bristol Myers Squibb: Current Employment, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Kang: BMS: Current equity holder in publicly-traded company. Civardi: Bristol Myers Squibb: Current Employment. Katz: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Maciag: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Hagner: BMS: Current Employment, Current equity holder in publicly-traded company. Pourdehnad: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties: No royalty. Bahlis: Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Genentech: Consultancy; BMS/Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria. Richardson: Oncopeptides: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Protocol Intelligence: Consultancy; Janssen: Consultancy; Sanofi: Consultancy; Secura Bio: Consultancy; GlaxoSmithKline: Consultancy; Regeneron: Consultancy; AstraZeneca: Consultancy; AbbVie: Consultancy; Jazz Pharmaceuticals: Consultancy, Research Funding. Thakurta: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties.

Background: Neutropenic fever is a life-threatening condition which is common in patients undergoing allogeneic/autologous hematopoietic cell transplantation (HCT) or chimeric antigen receptor - T cell (CAR-T) therapy. Empirical treatment includes monotherapy with a beta-lactam containing anti-pseudomonal activity. Nevertheless, stewardship of antibiotic in this vulnerable population is controversial. Methods: This was a single center, prospective, unblinded randomized study, of patients after HCT or CAR-T therapy that were enrolled between January 2020 and March 2021. Allocation was concealed in sequentially numbered sealed opaque envelopes. All patients signed informed consent and the study was approved by the Tel Aviv Medical Center Institutional Review Board. Patients were randomly assigned to receive either standard empiric antibiotic ( piperacillin/tazobactam or ceftazidime) that was continued until recovery of counts (control group), or standard empiric antibiotic that was discontinued after 48-72 hours providing there was no evidence of clinical or microbiology documented infection (intervention group). Rapid identification of bloodstream infections was performed with BioFire filmarray multiplex PCR assay (bioMerieux), and results were used to adjust antibiotic treatment early. The primary outcome was the percentage of days without empiric antibiotic (antibiotic-free-neutropenia days). Secondary outcome included successful response to treatment, defined as the combination of- continuation of clinical improvement on day 5 after initiation of antibiotic, no reoccurrence of bacetermia/fever/clinical infection signs on day 5, and no need for additional therapy on day 4-5 after starting antibiotic. Breakthrough fever, death within 30 days of episode onset, duration of hospitalization, duration of neutropenia, graft vs. host disease (GVHD) and characteristics of cytokine release syndrome (CRS) were also evaluated, as appropriate. Results: 110 patients were randomized to standard therapy (control group, n=51) and antibiotic stewardship strategy (intervention group, n=59), Figure 1. The patients' baseline characteristics were well-balanced between the 2 groups, Table 1. Febrile neutropenia occurred in 91 of the patients, and these patients were eligible for the per-protocol analysis. In the intention-to-treat population, the fraction of antibiotic-free neutropenia days was significantly higher for patients allocated to the stewardship arm, compared to those allocated to the standard arm (median [IQR], 0.8 [0.62-0.86] versus 0.51 [0.17-0.86], respectively, p=.0016). This was also true for the subgroups of patients treated per-protocol (median [IQR], 0.75 [0.61-0.83] versus 0.42 [0.12-0.72], respectively, p Conclusions: This is the first randomized study showing in a homogenous population of patients after cellular therapy, the safety of antibiotic stewardship. Optimization of antibiotic schedule is a widely available and cost-effective strategy to improve treatment outcomes in patients with high risk febrile neutropenia after cellular therapy. Figure 1 Figure 1. Disclosures Ram: Gilead: Honoraria; Novartis: Honoraria. Avivi: Kite, a Gilead Company: Speakers Bureau; Novartis: Speakers Bureau.

Background. We report here a trial in progress for the evaluation of a novel system aimed to provide an all-digital standardized bone marrow aspirate (BMA) analysis, Scopio Labs X100, empowered by artificial intelligence (AI) based cell pre-classification. Current methods for the analysis and reporting of BMA specimens are based on analog microscopy, as whole slide imaging at x100 magnification is not practically available. The lack of uniformity between experts in the field, originating from a subjective manual review, can lead to inconsistencies in disease diagnosis and classification, and thereby affect treatment and clinical outcomes. For example, ICSH and WHO guidelines require that at least 500 cells should be counted in at least two smears when a precise percentage of an abnormal cell type is required for diagnosis and classification. It is also recommended that in order reduce imprecision from sampling error, the total number of cells counted in the differential should be increased, specifically if the abnormal cell count is very close to a critical threshold for disease stratification or response assessment. For the general evaluation of hematopoiesis, Myeloid to Erythroid (M:E) ratio is reported. Considering the complexity of the manual BMA analysis, even more so in routine laboratory settings with competitive turnaround times, a digital transformation can sustain the desired standardization, and increase sensitivity and efficiency in routine workflow. Study Design and Methods. This multisite study is taking place at: Hospital of the University of Pennsylvania (HUP), Oregon Health and Science University (OHSU), and Tel Aviv Sourasky Medical Center (TASMC). BMA analysis is performed with a manual microscope as the reference arm and in Scopio Labs X100 Full Field BMA application as the test arm (Figure 1A). Two hematopathologists at each site independently review 265 BMA specimens, including 205 with a Romanowsky stain and 60 with a Prussian Blue stain, in both the test and the reference arms. There is a 3 week washout period between arms (Figure 1B, right). ICSH guidelines were rigorously translated into a comprehensive report format used in both study arms. The report presents 27 primary and 13 secondary characteristics for the morphological assessment of BMA (Figure 1C). These include evaluation of specimen quality, evaluation of count, maturation and morphology of trilineage hematopoietic elements (myeloid, erythroid and megakaryocytic), as well as lymphocytes and plasma cells. For a repeatability study, 8 representative samples are analyzed through 20 days, 2 daily runs and 2 replicas in one site. For reproducibility study, 8 representative samples are analyzed in all sites for 5 days with 5 replicas (Figure 1B, left). The collected BMA samples hold a distribution of 55.61% males, with 2.02%, 9.46%, 16.39%, 54.73% and 17.40% of ages 13-21, 22-39, 40-55, 56-75 and >75 respectively. All samples were diagnosed by WHO criteria. Diagnoses include AML, ALL, MPN, MDS, PCN, lymphoid neoplasms, aplastic anemia, ITP and normal morphology marrow and hemodiluted samples. All samples were retrieved from the sites' bone marrow sample storage. For the method comparison study, the primary and secondary characteristics are aggregated into three primary and secondary evaluation categories of specimen quality, count, and morphology and maturation assessments (Figure 1B, left, 1C). For the primary groups, confusion matrix will be produced. For the secondary groups, contingency tables will be generated (Figure 1B, left). For the repeatability and reproducibility (R&R) studies, two-way nested ANOVA tables will be created (Figure 1, right). Primary groups will be measured for accuracy in the form of efficiency, sensitivity and specificity. Secondary groups will be measured for overall agreement. R&R will be measured for SD and CV. The introduction of Scopio's full field morphological evaluation of BMA smears, promotes an accurate diagnosis of hematological disorders including hematological malignancies, and enables a remote evaluation of BMA smears. By reviewing the entire BMA smear, and by counting a very large number of cells, this novel approach provides a new and highly accurate tool for early detection of pathological conditions, including residual disease following therapy. Figure 1 Figure 1. Disclosures Bagg: Scopio Labs: Research Funding. Raess: Scopio Labs: Research Funding. Jengehino: Scorpio Labs: Other: Partial Salary Support. Wiszniewska: Scopio Labs: Research Funding. Huynh: Scorpio Labs: Other: Salary Support. Fan: Scopio Labs: Research Funding. Bhattacharyya: Scorpio Labs: Other: Partial Salary Support. Avivi: Novartis: Speakers Bureau; Kite, a Gilead Company: Speakers Bureau. Katz: Scopio Labs: Consultancy.

Background: Complete Blood Count (CBC) analytical capacity is falling short of recognizing informative RBC morphology or WBC dysplastic morphological changes. Current morphologic peripheral blood smear (PBS) analysis is performed manually using a semi-quantitative scale on a limited number of cells introducing high degree of subjectivity and low sensitivity. The novel Full-Field Morphology (FFM) technology developed by Scopio Labs performs PBS analysis on a significantly larger scale of 1000 fields of 100X view in a routine manner, allowing a precise and highly sensitive automated quantification of cellular and sub-cellular morphological parameters. Current diagnosis of myelodysplastic syndrome (MDS) is based on invasive bone marrow aspirate, followed by subjective morphological analysis. In this study, we applied this digital morphometric approach to compare PBS morphology of MDS patients with age-matched controls. Methods: 32 MDS (average age 80+10, [range 41-97] y, F:M ratio 14:18) and 30 age-matched control (average age 79+9, [range 65-100] y, F:M ratio 13:17) PBS were scanned by the Scopio Labs system, and evaluated according to three distinct morphological features with known significance in MDS: blast percentage per 100 or 1000 WBC; neutrophil cytoplasmic granulation per 1000 neutrophils; RBC morphology of at least 150,000 RBC. Quantitative determination of neutrophils granulation, was measured by Granulation Index (GI, between 0-1) and GI Distribution Width (GIDW, between 0-1). RBC measurements included the quantitative measurements of RBC size, namely macro- and microcytosis, and RBC contour changes (deformation), i.e. the percent of RBC that deviate from normal RBC shape. Results: The mean GI of MDS samples was 0.36+0.15, [range 0.14-0.63] (Fig. 1A middle, Fig. 1E), significantly (p Conclusion: Our study demonstrates that FFM-based digital PBS analysis enables the detection and quantification of unique WBC and RBC morphologic alterations associated with MDS. The expanding therapeutic options for MDS, including for patients at early disease stages, makes the establishment of an accurate diagnosis of MDS, even at early stages, to be highly important. The proposed novel digital imaging technology opens the opportunity to screen patients, diagnose them early, based on peripheral blood morphology, and potentially, monitor their responsiveness to therapy. Figure 1 Figure 1. Disclosures Katz: Scopio Labs: Consultancy. Karni: Scopio Labs: Current Employment. Shimoni: Scopio Labs: Current Employment. Natan: Scopio Labs: Current Employment. Shaham: Scopio Labs: Current Employment. Pozdnyakova: Scopio Labs: Consultancy. Mittelman: Janssen · Roche · Novartis · Takeda · Medison / Amgen · Neopharm / Celgene / BMS · Abbvie · Gilead: Research Funding; Novartis · Takeda · Fibrogen · Celgene / BMS · Onconova · Geron: Other: Clini; Onconova · Novartis · Takeda · Silence: Membership on an entity's Board of Directors or advisory committees; MDS HUB: Consultancy; Celgene / BMS · Novartis: Speakers Bureau. Avivi: Novartis: Speakers Bureau; Kite, a Gilead Company: Speakers Bureau.

SARS-COV-2 (COVID-19) has resulted in over 4 million deaths worldwide. While vaccination has decreased mortality, there remains a need for curative therapies for active infections. Uncertainties regarding the duration of post-vaccination immunity and the rapidity of mutational evolution by this virus suggest that it is unwise to rely on preventative measures alone. Humoral and cellular immunity provide selective pressure for the emergence of variant strains which have eliminated target epitopes. Elimination of immunodominant epitopes provides the strongest advantage to newly emerging strains and, consequently, immunodominant epitopes would be expected to be preferentially eliminated compared to subdominant epitopes in emerging variants. Immunologic treatments for SARS-COV-2 need to be continuously reassessed as new sequence information becomes available. TVGN-489 is a clinical grade product consisting of highly enriched, highly potent CD8+ CTLs recognizing peptides derived from COVID-19 gene/ORF products in an HLA restricted manner. CTLs are generated from apheresis products from individuals who have recovered from COVID-19 infections. Lymphocytes are serially primed and selected using APCs from these donors pulsed with small numbers of peptides encoded by the COVID-19 genome predicted or demonstrated to bind to specific HLA class I alleles. The resulting products are typically >95% CD3+/CD8+, >60% positive by tetramer staining and demonstrate strong cytolytic activity with >60% lysis of peptide pulsed targets typically at an effector to target ratio of 3:1 (See Figure). Given the immunologic pressure to lose dominant target epitopes, we assessed whether the peptides derived from genomic sequences from early SARS-COV-2 strains (and successfully used to generate CTLs from donors infected with these early strains) were still present in the more recently evolved Delta variant. Seven peptides were used to generate CTL products restricted by HLA-A*02:01, the most common allele worldwide. These peptides are derived from the spike (S) and nucleocapsid (N) proteins as well as ORF3a and ORF1ab. The contributions of these peptides to the overall cytotoxicity and tetramer staining range from 2% to 18% without clear immunodominance by one of these peptides. Though identified in early viral strains, these sequences persist in 97.5%-100% of the more than 120 Delta variant sequences present in the NIH database. For HLA-A*01:01, eight peptides derived from the matrix (M) protein as well as ORF1ab and ORF3a were utilized to generate CTLs. Seven of the eight peptides showed binding similar to what was seen with the HLA-A*02:01 peptides (1% to 18%). However, in contrast to HLA-A*02:01, an immunodominant peptide (TTDPSFLGRY, ORF1ab 1637-1646) was noted which was responsible for over half of the observed tetramer binding. This region of ORF1ab was mutated in the Delta variant resulting in loss of this immunodominant epitope from nearly 93% of the Delta genomic sequences in the NIH database. The remaining subdominant peptides were all preserved in 100% of the sequences. Given the growing number of Delta cases, it will be essential to remove this peptide from the HLA-A*01:01 peptide pool used to stimulate SARS-COV-2-specific CD8+ CTLs to avoid encouraging the expansion of cells which would recognize early strains of the virus, but not Delta variants. The remaining CTLs, generated in the absence of TTDPSFLGRY, should be capable of eradicating Delta as well as the earlier prototypic strains of COVID-19. The loss of immunodominant epitopes is not surprising in a virus such as SARS-COV-2, with a high frequency of mutation. This provides an example of immunologic escape similar to what has been described for the Delta variant in the case of HLA-A24. These data are consistent with the hypothesis that immunodominant epitopes will be preferentially eliminated as the virus continues to evolve. They further illustrate the need to monitor viral sequences and to tune the production of CTLs in order to ensure that they can continue to recognize and effectively treat newly emerging variants of COVID-19. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare. OffLabel Disclosure: The drug is Cytotoxic T lymphocytes that are specific to COVID-19. Preclinical data.

Relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL) is a family of aggressive lymphomas, with a median overall survival (OS) of less than 6 months. Current FDA approved therapies for R/R PTCL have modest overall response rates (ORR) of < 30%. Duvelisib (DUV), a dual PI3K-δ,γ inhibitor, is FDA approved at 25 mg twice daily (BID) for the treatment of R/R chronic lymphocytic leukemia and R/R follicular lymphoma. On 10/3/2019, DUV received orphan designation for treatment of patients with R/R T-cell lymphomas. In the Phase 2, open-label, multi-center, parallel cohort PRIMO trial of DUV in R/R PTCL, the initial results of the dose-optimization phase (N=33) demonstrated a 54% ORR in the 75 mg BID (N=13) and 35% in the 25 mg BID (N=20) cohorts, respectively, by investigator assessment (INV). (NCT03372057; supported by Secura Bio). The expansion phase of PRIMO has a targeted enrollment of ~125 pts. Expansion phase eligibility criteria included histologically confirmed R/R PTCL after >1 cycle of a prior standard regimen, a CD4 lymphocyte count of ≥ 50/mm 3 and required PJP prophylaxis. HSV/VZV prophylaxis was strongly recommended. Based on the dose optimization results, pts in the expansion phase receive DUV at 75 mg BID for 2 cycles to maximize rapid tumor control, followed by 25 mg BID to maintain long-term disease control and mitigate late toxicities, until progressive disease (PD) or unacceptable toxicity. The primary endpoint is ORR by IRC assessment, and secondary endpoints include ORR by INV assessment, duration of response (DOR), PFS, OS, disease control rate, and safety; all analyses consisted of pts that received at least 1 dose of DUV. This analysis is from an interim data cutoff as of May 21, 2021 that includes the first 6 months of data for the 78 patients included in the analysis. Pts had a median age of 66.5 years (range, 21-92 years) and a median of 3 prior lines of therapy (range, 1-7). The ORR by IRC assessment was 50% (39/78 patients) and the CR rate was 32.1% (25/78 patients), see Table 1. 14 patients (18%) remained on treatment; 37 pts discontinued due to PD (47.4%), 15 discontinued to due adverse events (19.2%) , 4 died (5.1%), and 1 each discontinued for secondary malignancy, lack of response, and withdrawal of consent. 5 patients (6.4%) discontinued therapy to undergo stem cell transplant, which suggests that DUV may be used as a bridge to transplant for appropriate patients. There were 3 deaths related or possibly related to duvelisib: pneumonitis, Epstein-Barr associated lymphoproliferative disorder, and sepsis. The most frequent > Grade 3 adverse events seen were neutropenia (38.5%), ALT/AST increased (24.4%/ 21.8%), rash (7.7%), lymphocyte count decreased (7.7%), and sepsis (6.4%), see Table 2. ALT and/or AST elevations were the most common AEs leading to treatment discontinuations (N=12, 15.4%). The interim results of the first 78 patients in the PRIMO expansion phase show an ORR of 50% and a CR rate of 32%, which suggests this therapy is superior to currently available SOC therapeutic options. Duvelisib was well tolerated in this population and remained consistent with the known safety profile of DUV. These data, from a large diverse population of T cell lymphoma patients, build upon prior reports demonstrating DUV as an active oral treatment for pts with RR PTCL. Data from this interim analysis may be updated prior to the abstract presentation. Figure 1 Figure 1. Disclosures Brammer: Celgene: Research Funding; Kymera Therapeutics: Consultancy; Seattle Genetics: Speakers Bureau. Zinzani: BMS: Other: Advisory board, Speakers Bureau; ROCHE: Other, Speakers Bureau; SANDOZ: Other: Advisory board; ADC Therap.: Other; SERVIER: Other: Advisory board, Speakers Bureau; JANSSEN-CILAG: Other: Advisory board, Speakers Bureau; GILEAD: Other: Advisory board, Speakers Bureau; CELLTRION: Other: Advisory board, Speakers Bureau; EUSAPHARMA: Consultancy, Other, Speakers Bureau; TAKEDA: Other: Advisory board, Speakers Bureau; KYOWA KIRIN: Other, Speakers Bureau; NOVARTIS: Consultancy, Other, Speakers Bureau; TG Therapeutics: Other: Advisory board, Speakers Bureau; MSD: Consultancy, Other: Advisory board, Speakers Bureau; Incyte: Other, Speakers Bureau; Beigene: Other, Speakers Bureau; VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau. Zain: Secura Bio, Ono , Legend, Kiyowa Kirin, Myeloid Therapeutics Verastem Daichi Sankyo: Consultancy; Secura Bio, DaichiSankyo, Abbvie: Research Funding; Kiyoaw Kirin, Secura Bio, Seattle Genetics: Honoraria. Casulo: BMS: Research Funding; Verastem: Research Funding; Genentech: Research Funding; Gilead: Research Funding. Jacobsen: Takeda: Consultancy; Syros: Consultancy; Janssen: Research Funding; Novartis: Research Funding; Pharmacyclics: Research Funding; Acerta: Research Funding. Gritti: Takeda: Consultancy; Roche: Consultancy; Kite Gilead: Consultancy; IQvia: Consultancy; Italfarmaco: Consultancy; Clinigen: Consultancy. Litwak: Secura Bio: Current Employment. Cohan: Secura Bio: Current Employment. Katz: Secura Bio: Current Employment. Mehta-Shah: C4 Therapeutics: Consultancy; Roche/Genentech: Research Funding; Kiowa Hakko Kirin: Consultancy; Karyopharm: Consultancy; Innate Pharmaceuticals: Research Funding; Celgene: Research Funding; Bristol Myers Squibb: Research Funding; AstraZeneca: Research Funding; Daiichi Sankyo: Consultancy, Research Funding; Secura Bio: Consultancy, Research Funding; Ono Pharmaceuticals: Consultancy; Corvus Pharmaceuticals: Research Funding; Verastem: Research Funding. Horwitz: ADC Therapeutics, Affimed, Aileron, Celgene, Daiichi Sankyo, Forty Seven, Inc., Kyowa Hakko Kirin, Millennium /Takeda, Seattle Genetics, Trillium Therapeutics, and Verastem/SecuraBio.: Consultancy, Research Funding; Affimed: Research Funding; Aileron: Research Funding; Acrotech Biopharma, Affimed, ADC Therapeutics, Astex, Merck, Portola Pharma, C4 Therapeutics, Celgene, Janssen, Kura Oncology, Kyowa Hakko Kirin, Myeloid Therapeutics, ONO Pharmaceuticals, Seattle Genetics, Shoreline Biosciences, Inc, Takeda, Trillium Th: Consultancy; Celgene: Research Funding; C4 Therapeutics: Consultancy; Crispr Therapeutics: Research Funding; Daiichi Sankyo: Research Funding; Forty Seven, Inc.: Research Funding; Kura Oncology: Consultancy; Kyowa Hakko Kirin: Consultancy, Research Funding; Millennium/Takeda: Research Funding; Myeloid Therapeutics: Consultancy; ONO Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Research Funding; Secura Bio: Consultancy; Shoreline Biosciences, Inc.: Consultancy; Takeda: Consultancy; Trillium Therapeutics: Consultancy, Research Funding; Tubulis: Consultancy; Verastem/Securabio: Research Funding. OffLabel Disclosure: Duvelisib is approved in relapsed/refraction CLL/SLL and FL. This study evaluates duvelisib in PTCL

Background Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease associated with major complications such as thrombotic events and impaired renal function. Prior to the introduction of C5 inhibitors in 2007, PNH had been fatal in about 35% of patients within 5 years of diagnosis; yet, this fatality rate continues in countries without access to these medications. Worldwide access to the C5 inhibitor eculizumab is hindered by the unavailability of treatment, and in places where treatment is approved, cost of treatment, reimbursement issues, infrastructure, or patient restrictions may further impede access (Risitano et al, Am J Hematol. 2018; Risitano et al, Front Immunol. 2019). PNH treatment places a significant economic burden on healthcare systems. In a number of countries, this has resulted in negative health technology appraisals (HTAs), indicative that optimal care and resource utilization are not being achieved (Coyle et al, Med Decis Making. 2014). New therapies with more convenient modes of administration may have the potential to improve how PNH is clinically treated and may have a positive effect on the economic burden and access to C5 inhibitors globally. Robust data on the real-life burden and cost of PNH are therefore needed to assess the impact of current therapies and establish a baseline for new therapeutic approaches. The data derived from this study will be used to support HTA processes and inform the value of new therapies for PNH. Objectives The COMMODORE Burden of Illness (BOI) study will quantify the direct medical costs (eg, treatment and hospitalization), direct nonmedical costs (eg, travel), and indirect costs (eg, impact on work productivity and family burden) associated with PNH for patients and care providers and determine the impact of PNH on health-related quality of life (HRQoL). Study Design and Methods This is an international, prevalence-based, bottom-up, burden of illness study containing both retrospective and prospective data collection. The study will be overseen by an expert reference group consisting of multidisciplinary stakeholders. The study protocol and materials will be submitted for ethical approval to the University of Chester in the United Kingdom. Physicians will provide information on sociodemographic, clinical, and medical resource utilization using an electronic case record form (eCRF). Through patient and public involvement and engagement, patients, after giving informed consent, will provide further information on the economic and HRQoL impact of PNH by completing patient-reported outcome surveys. Patients from France, Germany, United Kingdom, and China will be included. The study aims to recruit 94 physicians reporting 350 patient eCRFs with an expected return of 140 patient surveys and longitudinal data collection after 6 to 12 months for each patient. Mean per-patient costs, including direct medical and nonmedical costs, and indirect resource utilization will be calculated by multiplying the individual resource utilization with country-specific unit costs. National economic burden will be extrapolated by applying national prevalence estimates of PNH. Additionally, the impact of PNH on HRQoL in patients will be assessed within this study. Summary The COMMODORE BOI study aims to characterize current PNH treatment via quantification of the humanistic and socioeconomic burden at the patient, healthcare system, and societal level to enhance the evidence base for treatment and decision-making in this community. Final results are expected be available by the second quarter of 2022. Disclosures Hampton: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Katz:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Shang:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Dhillon:F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. ; HCD Economics: Current Employment. Hubberstey:HCD Economics: Current Employment; Huntingdon's Disease Youth Organization: Membership on an entity's Board of Directors or advisory committees; F. Hoffmann-La Roche Ltd: Other: All authors received editorial support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. .

Complete blood count (CBC) analysis is one of the most commonly ordered laboratory tests and is a critical first step in patients' clinical evaluation. However, CBC analyzers are limited in their ability to positively identify several types of white blood cells (WBC), and cells with substantial clinical significance, such as immature granulocytes or blasts, are merely marked as flags. Also, CBC analyzers fall short of recognizing informative red blood cell (RBC) morphology, such as schistocytes, and often provide inaccurate platelets count. Flags and clinically non-sufficient CBC-derived data reflex to generation of blood smear (BS), and BS review comprises a substantial portion of the workload in routine hematology laboratories. For accurate identification and classification of WBC, BS analysis (BSA) requires detailed observation of cells with high-magnification objective (60-100X), which provides a relatively narrow Field of View (FOV). This physical limitation restricts current BSA to either low resolution/wide FOV or to high resolution/narrow FOV data generation (Fig. 1A). Hence, key issues of BSA such as the effects of the smearing process on the distribution of blood components, the effects of cells distribution on their morphology and further classification, as well as many other attributes, are addressed only qualitatively or empirically, leaving the real topology of the BS obscure. The computational imaging microscopy system presented herein uses a low resolution and wide FOV objective, and records a plurality of images under different illumination conditions, of the same sample area (Fig. 1B). An algorithm reconstructs a high resolution and aberration free image of whole specimens, as can be observed in the attached link (https://tinyurl.com/Scopio-Labs-X100-ASH-2020). High resolution images are critical not only for manual BSA, but also for artificial intelligence (AI)-derived BSA, since data quality is of prime importance for deep-learning processes, and to a large extent determine their outcome. Thus, the combination of high resolution/wide FOV turns each BS into a big data analytic field, rendering the measurement of yet undetermined cell characteristics. In order to elucidate the basic topology, 60 normal BS (28 females, 32 males) were subjected to analysis utilizing this novel computational imaging microscopy. For convenience of analysis and comparison with current BSA methodology, BS were segmented into strips according to RBC density (Fig. 1C, D). The average length of smear from females (F) was higher by nearly 28% compared with smear from males (M), and the presence of acute inflammation (A) resulted in a significant 33% increase in overall smear length compared to normal (N) average (Fig. 1E). As expected, RBC density formed a linear gradient (Fig. 1C) along the axis of sample smearing, however, RBC morphology was affected by location within the BS. For example, strips 4-5 contained RBC with the appearance of spherocytes (Fig. 1F; arrows), while in strips with increased RBC density, cells aggregated resembling rouleaux formation (Fig. 1F; arrowheads). Platelets distribution was non-linear, with only a few of them reaching the feathered edge of the smear (Fig. 1G). Since the variance of both RBC/FOV and platelets/FOV concentrations drops starting with strip 4, BS-derived platelets number estimates should not be performed in strips 1-3. On average, a normal BS contains 890+399 WBC in the scanned area (strips 1-8). Similar to RBC, the location of individual WBC throughout the BS may affect their morphology, and hence their classification. WBC in the feathered edge (strips 1-3) are generally more stretched, and often squeezed between RBC, rendering their classification by AI-based tools challenging (Fig. 1H). In strips 4-7, WBC morphology is optimal for a classification task, enabling favorable outcomes for either manual or AI cell analysis (Fig. 1H). These data indicate that BSA can be taken to a sensitivity level of at least 10-3 of WBC analysis, provided that a large portion of the BS is scanned. Our system provides a novel combination of computational imaging microscopy and AI-based classification tools to unravel the complex topology of blood smears, and upgrade the data obtained in BSA. This approach enables the establishment of quantitative rules to scientifically direct the objective analysis of cellular blood components both manually, and by AI-tools. Figure Disclosures Katz: Scopio Labs: Consultancy.

Background Paroxysmal nocturnal hemoglobinuria (PNH) is a life-threatening disease of dysregulated complement activation characterized by hemolysis and thrombosis and is associated with bone marrow failure. PNH can also impair patient quality of life and negatively impact the ability to work. PNH is a rare disease with an estimated incidence of 1 to 1.5 cases per million people globally. Inhibition of complement component 5 (C5) has been shown to reduce intravascular hemolysis, stabilize hemoglobin, reduce the need for blood transfusion, and improve quality of life for patients with PNH. C5 inhibitors eculizumab and ravulizumab are approved in the United States and other countries for treatment of PNH, yet there are limited data on the real-world use of these agents, especially in populations not eligible to participate in registrational clinical trials. Here we describe the COMMODORE Cohort study, which will use a novel patient-centered study design to collect both retrospective and prospective patient data on the real-world use, safety, and effectiveness of eculizumab and ravulizumab, as well as disease burden and outcomes, in patients with PNH in the United States. Study Design and Methods This noninterventional cohort study will collect data using the PicnicHealth digital personal health record platform. This platform uses a novel human-in-the-loop machine learning system to integrate, harmonize, and structure patient data, including clinical notes, medications, laboratory results, and diagnostic reports contained in medical records collected from any healthcare facility in the United States. This study was designed in collaboration with patient advocacy groups to ensure that data generated will answer questions important to the patient community. In contrast to many studies, patients will be directly recruited to participate through multiple avenues, including working with patient advocacy groups and societies as well as outreach through social media and other communication tools. All patients must complete an informed consent form to participate. Patient data is anonymized, and the study complies with the Health Insurance Portability and Accountability Act data security standards. The study will be submitted to IntegReview for institutional review board approval. Patients who report a diagnosis of PNH within the past 5 years and have subsequently been treated with eculizumab or ravulizumab can be included in this study (Figure). Data extracted by the platform will confirm that the patient meets study criteria. The study has 3 arms: arm A is comprised of patients who initiated therapy with eculizumab, arm B is patients who initiated therapy with ravulizumab, and arm C is patients who initiated therapy with eculizumab and later switched to ravulizumab. Exclusion criteria for patients in arms A and B includes treatment with a complement inhibitor prior to PNH diagnosis and treatment with eculizumab or ravulizumab for > 25 weeks. Exclusion criteria for all patients include platelet count < 30,000/μL, absolute neutrophil count < 500/μL, and history of bone marrow transplant. The primary objective is to describe the proportion of patients who do not receive packed red blood cell transfusion. Secondary objectives are to determine the proportions of patients with breakthrough hemolysis, stabilized hemoglobin, and a thromboembolic event and the change in normalized lactate dehydrogenase. Safety objectives are to determine the rates and proportions of selected adverse events. Primary, secondary, and safety objectives will be evaluated from week 5 to 25 of treatment. The effectiveness and safety analyses will be conducted in all patients who fulfill entry criteria and have a minimum of 25 weeks of accrued person-time from treatment initiation. Exploratory analyses assessing long-term experiences and outcomes and will be conducted in all patients who fulfill entry criteria with no minimum treatment duration requirement. Descriptive statistics will be provided. Summary The COMMODORE Cohort study will use a novel, patient-centered approach to data generation including collaborating with patient groups to ensure that the study answers questions important to the PNH community. This approach may serve as a model for future studies evaluating other rare diseases with limited real-world data. Disclosures Shang: F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Faghmous:Kite Pharma: Current Employment; F. Hoffmann-La Roche Ltd: Ended employment in the past 24 months, Other: All authors received medical writing support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. . Drozd:PicnicHealth: Current Employment, Current equity holder in private company; F. Hoffmann-La Roche Ltd: Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Katz:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland..

Background Paroxysmal nocturnal hemoglobinuria (PNH) is a life-threatening disease of dysregulated complement activation. It is a rare disease with an estimated incidence of 1 to 1.5 cases per million people globally. Eculizumab is a humanized monoclonal anti-complement component 5 antibody that was approved for the treatment of patients with PNH in the United States and European Union in 2007, yet unmet medical needs remain. Up to half of patients continue to require blood transfusions despite treatment with eculizumab, and hemolytic activity remains detectable in many patients (Brodsky et al. Blood. 2008). Eculizumab is not available in many countries. In places where treatment is approved, there are further impediments to access, such as cost of treatment, reimbursement issues, infrastructure limitations, and patient restrictions (Risitano et al. Am J Hematol. 2018; Risitano et al. Front Immunol. 2019). Data published on real-world outcomes of eculizumab are limited. Here we describe a study that will retroactively analyze data from patients with PNH treated with eculizumab at the Essen University Hospital in Germany. Study Design and Methods This retrospective, secondary data use, cohort study will include all patients at the Essen University Hospital who were diagnosed with PNH and treated with eculizumab prior to April 2018. Clinical data from medical records were entered into an electronic case report form (eCRF). Source data verification has been performed for all clinical data. Laboratory data were extracted directly from the hospital computer system. The Essen University hospital also checked and verified missing laboratory data. Patient-level data in the eCRF and laboratory data were fully anonymized. The primary objective of the study is to understand the remaining unmet medical need by describing the eculizumab dose and frequency of dose adjustment and describing the proportions of patients who experience intravascular and extravascular hemolysis while on treatment. The secondary objectives include explorations of the association between lactate dehydrogenase (LDH) and hemoglobin stabilization with clinical outcomes (eg, breakthrough hemolysis and the need for red blood cell transfusion), the association between PNH clone size and clinical outcomes and the risk of thrombosis, the changes in LDH and hemoglobin levels over time, the need for red blood cell transfusion during eculizumab treatment, and the proportion of eculizumab-treated patients with positive monospecific Coombs test results. In addition, opportunities to apply machine-learning methodologies to predict patients who may not respond to eculizumab will be explored. Many of the analyses will be descriptive. The associations between LDH and hemoglobin with clinical outcomes will be evaluated using rank correlation coefficients or logistic regression. Multivariable regression will be used to explore the prognostic value of clone size on clinical outcomes and thrombosis events. This retrospective study includes 85 patients with PNH with complete clinical and laboratory data (Table). The median age of the cohort was 38 years old, and the cohort was split evenly between men and women. Many patients received a diagnosis of PNH prior to the availability of eculizumab, as the year of diagnosis was 2010 or earlier for 53 patients (62%). The median years of follow-up from initiation of eculizumab was 4.7 years. Overall, 34% had aplastic anemia at diagnosis, and symptoms of fatigue, abdominal pain, and kidney failure were reported in 60%, 34%, and 15%, respectively. At data cutoff, 92% of patients were still alive. Summary The patient demographics in this study are comparable to other studies in PNH, suggesting a representative population. With median follow-up time of nearly 5 years, this study will allow for a long-term assessment of the patient experience with eculizumab. High-quality study data is ensured via full source data verification of clinical data and verification of missing laboratory data. These study results will help to address many research questions in PNH, identify the remaining unmet medical need, and also inform new drug development. Disclosures Versmold: F. Hoffmann-La Roche Ltd: Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Raiser:F. Hoffmann-La Roche Ltd: Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Faghmous:F. Hoffmann-La Roche Ltd: Ended employment in the past 24 months, Other: All authors received medical writing support for this abstract, furnished by Scott Battle, funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. ; Kite Pharma: Current Employment. Katz:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Shang:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Xu:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Röth:Novartis: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Biocryst: Consultancy, Honoraria; Apellis: Consultancy, Honoraria; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Research Funding.