Background Daratumumab-based treatment regimens for MM have improved outcomes for both transplant-eligible and ineligible patients. As a result, patients are receiving longer exposure to this CD38 targeting monoclonal antibody. Adverse events (AE) including hypogammaglobulinemia, neutropenia, and lymphopenia have been reported in both clinical trials and retrospective studies, but with limited and contrasting data on the associated risk of developing infections. Furthermore, there remains a paucity of data on the risk of developing opportunistic infections in this growing patient population. The aim of this study is to assess the association between daratumumab-containing regimens and the development of opportunistic infections as reported to the Food and Drug Administration's Adverse Events Reporting System (FAERS), a pharmacovigilance monitoring database. Methods/Materials FAERS was queried for AE reports to evaluate the association of Cytomegalovirus reactivation (CMVr), Hepatitis B reactivation (HBVr), progressive multifocal leukoencephalopathy (PML), Herpes Zoster (HZ), Tuberculosis (TB), Pneumocystis Jirovecii (PJP), and Bronchopulmonary Aspergillosis (BA) with daratumumab-containing regimens from 2015-2021. The strength of an association between an infection reported with daratumumab in MM was compared with all events reported in MM treated patients, and the composite of all reported AE cases in FAERS. Signal disproportionality was calculated by using the reporting odds ratio (ROR), with the precision of the ROR determined by 95% confidence intervals (95% CI). Associated p-values were calculated by using chi-squared or Fisher's Exact test, with a p-value <0.05 considered statistically significant. Other reported variables concomitantly reported with daratumumab-treated patients were collected, including reported chemotherapy, >1 MM regimen, proteasome inhibitor (PI) use, or lenalidomide use. Results Out of the 12,393,747 AE cases reported to FAERS, there were 288,294 (2.3%) AE reported with MM patients, of which 7,152 (2.5%) were reported with daratumumab. There were 195 (2.7%) opportunistic infections reported with daratumumab, with a median age of 64 (42-89) years, and 64 (32.8%) were females. HZ (N=49, 25.1%) was the most common, followed by CMVr (N=43, 22.0%), PML (N=35, 17.9%), PJP (N=34, 17.4%), BA (N=16, 8.2%), HBVr (N=13, 6.7%), and TB (N=5, 2.5%). Neutropenia was reported in 29 (14.9%) of these patients, lymphopenia in 6 (3.1%), and hypogammaglobulinemia in 1 (0.51%) case. With comparison to all reported events in the FAERS database, a significant signal disproportionality was found with HZ (ROR 3.48 [95% CI 2.63, 4.61], p<0.0001), CMVr (ROR 33.31 [95% CI 24.61, 45.08], p<0.0001), PML (ROR 16.69 [95% CI 11.96, 23.31], p<0.0001), PJP (ROR 12.87 [95% CI 9.18, 18.05], p<0.0001), BA (ROR 9.82 [95% CI 6.01, 16.06], p<0.0001), and HBVr (ROR 9.35 [95% CI 5.42, 16.14], p<0.0001). When comparing reported infections with AE associated with MM patients in FAERS, HZ (ROR 1.59 [95% CI 1.19, 2.11], p=0.0015), CMVr (ROR 28.82 [95% CI 19.44, 42.72], p<0.0001), PML (ROR 13.04 [95% CI 8.89, 19.12], p=<0.0001), PJP (ROR 9.58 [95% CI 6.59, 13.96],p<0.0001), BA (ROR 11.46 [95% CI 6.56, 20.01], p<0.0001), HBVr (ROR 4.41 [95% CI 2.49, 7.83],p<0.0001), and TB (ROR 6.15 [95% CI 2.39, 15.78], p<0.0001) met statistical significance (Table 1). The proportion of concomitant medications reported with daratumumab is reported in Figure 1. Conclusion This study suggests a significant association between daratumumab-based regimens and multiple opportunistic infections. Patients with known chronic viral infections or who are heavily pretreated should be monitored for these potential complications. FAERS data is beneficial in reporting associations between medications and AE but does not necessarily indicate causality. Further studies are needed to corroborate these findings. Figure 1 Figure 1. Disclosures Ganguly: Kadmon: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Membership on an entity's Board of Directors or advisory committees; Bristol Myer Squibb: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees.

Background Factor VII (FVII), a vitamin K-dependent glycoprotein serine protease, is produced by the liver and plays a fundamental role in the activation of the extrinsic coagulation pathway. Hereditary factor VII deficiency is a rare coagulation disorder with autosomal recessive inheritance and an approximate prevalence of 1:500,000. Clinical manifestations vary from no symptoms to severe bleeding events and often correlate poorly with plasma levels of factor VII. Therapy for factor VII deficiency depends on the severity and the type of bleeding and includes fresh frozen plasma (FFP), antifibrinolytics and recombinant factor VIIa (rFVIIa). Recent data from the STER registry suggests that bleeding symptoms on presentation and factor VII activity level can be used to identify clinical variants and guide replacement therapy. The majority of patients enrolled in this registry were from European countries. Patients of African American origin remain poorly characterized. Aims We present our experience with diagnosis and management of patients, predominantly African American, in a large academic institution. We retrospectively reviewed the data on seven patients diagnosed with isolated factor VII deficiency and their management. Results Six of the seven patients followed in our institution were African American. Of them, three were female and three were male. A six month old girl was diagnosed during treatment for sepsis. She had no bleeding symptoms (FVII activity 27% on presentation, 32% one month later). The other two female patients presented with obstetrical bleeding (FVII <3% and 11% respectively). Of the male patients, two six year old twins had epistaxis (FVII activity 12%). Another six year old boy presented with trauma-associated hemorrhage, but had no prior history of bleeding (FVII 4%). Follow up data were available on five of the patients. Duration of follow up ranged from 6 months to more than 10 years. None of the patients had spontaneous bleeding, regardless of their presentation or level of FVII activity. The patients with bleeding and those who needed surgery received FFP (two patients prior to making the diagnosis) and rFVIIa (four patients). The doses used were 10-25mcg/kg in one or two applications. No bleeding and no thrombotic complications were observed with this therapy. None of the patients received antifibrinolytics. The one White Caucasian patient was a 25 year old male who presented with bleeding after trauma (FVII activity was 10%) and was managed with rFVIIa (25mcg/kg). Conclusion Our data demonstrates that, in African American patients, factor VII deficiency presents with variable clinical findings. There was poor correlation between the FVII levels and the clinical phenotype. Management with rFVIIa, used at the time of surgery or trauma at low to intermediate doses, was sufficient to prevent bleeding and was not associated with any significant complications. Disclosures: No relevant conflicts of interest to declare.

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4638 Thrombotic thrombocytopenic purpura (TTP), a syndrome characterized by thrombocytopenia and microangiopathic hemolytic anemia due to deficiency of the von Willebrand factor cleaving protease ADAMTS13, was once a highly fatal condition, but therapeutic plasma exchange (PEX) has dramatically improved outcomes. We report the results of a retrospective chart review of TTP patients treated with PEX at our institution from September 2006 through December 2011. Complete demographic, clinical, laboratory, treatment, and response data were collected to examine the influence of race on clinical outcomes. A total of 49 patients were treated for TTP. This cohort was predominantly female (71%) and African American (61%). Three patients were of Hispanic ethnicity. The median age was 50 years (14–81), and the median number of comorbidities at presentation was 4 (range 0–14). Assays for ADAMTS13 activity with reflex to ADAMTS13 inhibitor were performed by the Blood Center of Wisconsin. All patients were treated with PEX (1–1.5 plasma volume using fresh frozen plasma as replacement fluid) once daily until plateau in the platelet count, and then PEX frequency was tapered over 2 weeks in remitting patients. The median number of PEX procedures for the first episode was 8 (1–22). The median total PEX for all episodes was 9 (1–56). The majority of patients, 37 (75.5%), received corticosteroids, and rituximab was administered to 19 (38.8%) of patients at some point during their treatment, usually for slow response or relapse. An initial response to PEX, defined by normalization of platelet count (above 140×109/L) and resolution of signs of hemolysis, was achieved in 36/49 (73.5%) patients. The response rate was not significantly different between African Americans (73.3%) and Caucasians (68.8%, p=0.742), and all 3 Hispanic patients responded to initial treatment. Pre-treatment ADAMTS13 activity was severely deficient (<10% of normal) in 20/39 (51.3%) patients. An inhibitor of ADAMTS 13 was detected (>0.4 Inhibitor Units) in 19/23 (82.6%) patients tested. African Americans were more likely to have severely deficient ADAMTS13 activity (16/25, 64%) than Caucasians (2/13, 15.4%; p=0.004). The initial response rate was higher in patients with severely deficient ADAMTS 13 activity (90.0%) in comparison to those with >10% activity (68.4%), however the difference did not reach statistical significance (p=0.067). Of the patients with severely deficient ADAMTS 13 activity and detectable inhibitor levels, 89.5% had an initial response to PEX. All four patients with severely deficient ADAMTS 13 activity but undetectable inhibitor levels also responded to PEX. The total number of relapse events was 16 (32.7%), and the median time to relapse was 19.4 months. All three Hispanic patients, 4 (25%) Caucasians, and 9 (30%) African Americans relapsed. One-year relapse free survival was similar among Caucasians and African Americans at 72% and 75% respectively (p=0.852). All three Hispanic patients relapsed within the first year. One-year overall survival was similar for Caucasians and African Americans at 81.3% and 83.3% respectively (p=0.968). A total of 10 deaths were documented. The causes of death were relapse of TTP (3/10), sepsis (4/10), GI bleeding (2/10), and unknown etiology (1/10). In this unusual TTP cohort with 61% African Americans, we found that African Americans were more likely to have severely deficient ADAMTS13 activity than Caucasians, but response to PEX, relapse, and survival for Caucasian and African Americans were very similar. This study also supports pre-treatment assays for ADAMTS13 activity and its inhibitor, not only for the diagnosis of TTP, but also for predicting response to PEX therapy. Disclosures: No relevant conflicts of interest to declare.