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Introduction: The blood transfusion (BT) system in Pakistan is fragmented, demand-driven, and depends on weakly regulated transfusion practices. This is primarily a big problem in smaller cities and remote rural areas. Pakistan has one of the highest hepatitis B virus (HBV) and hepatitis C virus (HCV) prevalence worldwide, estimated around 5 & 10 million cases, respectively. There is a considerable risk that transfusion-transmissible infections (TTIs) may have contributed to the current epidemic of HBV & HCV, affecting 7.4 % of the general population, and potential risk of HIV transmission in the country. In this systematic review, we aim to identify the prevalence of TTIs among the blood donor population and associated safety challenges. Method & Material: We conducted a systematic literature search to identify studies related to TTIs and transfusion safety in Pakistan from January 1, 2010, to January 31, 2020. A search was conducted using PubMed and PakMedinet.com (largest medical database of Pakistan); initial search retrieved 981 articles, 166 met the inclusion criteria, and after review by two independent reviewers, 33 articles met the final criteria for qualitative synthesis. Results: Analysis of 33 studies showed the seroprevalence of HBV of 2.04 % (0.81% to 4.22%), HCV of 2.44% (1.29 % to 10%), HIV of 0.038% (0% to 0.18%), syphilis of 1.1% (0.11-3.01%) and malaria of 0.11% (0.05-1.20). The rate of coinfections among blood donors varied from 0.0099% to 0.35 %. The highest number of coinfections were HCV & syphilis, followed by HCV & HBV infections. The rate of TTIs was dependent on the number of donors, donor types (replacement vs. voluntary), screening techniques used, number, and type of TTIs tested. There was a lack of universal screening for common TTIs. Syphilis and malaria were tested only 38 % & 46 % of all the blood donations. The studies with a high number of replacement donors (RDs) noted a high prevalence of TTIs of 2.5 % to 12 % compared to the studies with a high number of voluntary non-remunerated donations (VNRDs) reported TTIs rates of 1.57% to 6.2 %. There was a significant difference in the prevalence of HBV & HCV in VNRDs (0.48%) compared to RDs (4.15%). The rate of VNRDs was 0.10 % to 13%. The majority of blood donations were from male donors, representing more than 70 % of all donations. The female donations varied from 0.03% to 15 % in government/public blood banks than 29 % in private sector blood banks. The HBV & HCV infections and anemia were the most common causes of blood donation deferral. The 69.5 % of donors who tested positive for TTIs in a study reported previous blood donations. The educational status of donors noted to have an association with knowledge about the risk of TTIs. Odds of having limited knowledge about TTIs (OR: 4.04, CI: 1.567-10.435, p Conclusion: This systemic review shows a high prevalence of TTIs, especially HBV, HCV & syphilis in the blood donor population. There is a high dependency on RDs, with minimal use of healthy voluntary blood donation practices, inadequate screening of high-risk donors, repeated collections of the blood from RDs, poor quality of screening methods, and limited knowledge of donors about their health. There is a lack of widespread standardized testing and follow up of patients who tested positive on initial testing. Large prospective multicenter clinical trials are required for a better understanding of the TTIs by testing and creating a follow-up system for both blood donors and recipients. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

Introduction: β-thalassemia major (TM) is one of the most prevalent inherited hemoglobinopathies in Pakistan. It has one of the highest prevalence of transfusion-dependent TM patients globally, with an estimated greater than 100,000 active cases. Each year, an estimated 5000-9000 new cases of TM are being diagnosed in the country. Blood transfusions (BT) are essential in the management of severe TM; it is critical to have a safe BT to reduce the risk of transfusion transmissible infections (TTIs). Frequent blood transfusions in these patients increase their risk of acquiring TTIs compared to the general population. In this systematic review, we aimed to identify the prevalence of TTIs in transfusion-dependent β -thalassemia major patients in Pakistan. Methods & Material: We performed a systematic literature search to identify studies related to the TTIs and transfusion-related infections in Pakistan from January 1, 2010, to January 31, 2020. The search was conducted using PubMed and PakMediNet (Largest medical database of Pakistan), with initial search retrieved 981 studies. Among these, 166 studies met the inclusion criteria. After further screening by reviewing the articles for relevance and availability of full-length articles, only 14 studies met the final criteria for qualitative synthesis. Results Analysis of 14 studies (n=3786) showed that the seroprevalence of Hepatitis B virus (HBV) of 3.13% (0.66 % to 7.4%) and Hepatitis C virus (HCV) of 26 % (5.56% to 68.2%). There were only two studies reported HIV seroprevalence of 0 % & 0.5% (n=6). The rate of seropositivity for HBV and HCV was directly related to the number of transfusions, higher ferritin levels, and older age groups. There was an increase in the HCV rate with the increasing age of patients. Thalassemia patients who were older than ten years of age had a greater HCV compared to those who were less than ten years of age, i.e., 22% vs. 8.4%, p:0.005, respectively. The mean age was higher in HCV reactive children than non-reactive children. A comparison of HCV in healthy donors vs. thalassemia patients showed a rate of 1.9% vs. 13.1% for T.M. patients. There was HCV infection rate of 74% in the group with greater than 100 BTs compared to 33 % in a group with fewer than 35 BTs. The rate of HCV increased to 75% for the patients who had more than 100 BTs. The majority of the patients were males (51% to 88%). The seroprevalence of TTIs was higher in males than in females (73.4% vs. 26.6%). On average, a single TM patient is exposed to at least 17 different donors annually, requiring 1-2 transfusions every month. The free BT is accessible only in 1 out of 4 thalassemia centers. The majority of patients either need to bring their donors or are dependent on an external source of financial aid as they could not afford the cost of BT treatment. More than half of thalassemia patients (57.2%) need to contact multiple BT centers to search for required blood products. About 42.1% of parents of TM patients did not know about TTIs, whereas 31.6% of them did not know about the bloodborne transmission of HBV and HCV. The majority of parents of TM children had a low income, with 75% of them having income less than 10,000 Pakistani rupees (PKR) per month. The prevalence of TTIs in TM patients was significantly higher (96% vs. 4%) compared to the patients requiring multiple transfusions due to other causes such as leukemia, aplastic anemia, and thrombocytopenia. Conclusion: Our data highlights that the prevalence of transfusion-transmitted infections, especially HCV, is alarmingly higher (26%) in the TM population than in the general population. This is because of a lack of resources, inadequate safety measures, and a fragmented blood transfusion system. These findings warrant the urgent need for better public health measures, safe blood transfusion practices, voluntary remunerated blood-based transfusions, and universal quality-assured donor screening. Without these positive interventions, the current transfusion system can lead to a further worsening of the situation. Large prospective multi-centered clinical trials are required to understand better the high prevalence of TTIs in patients with TM. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

Introduction: Amyloidosis is a disorder where misfolded proteins get deposited in different tissues. The most common of them is immunoglobulin light chain (AL) deposition, otherwise known as AL amyloidosis. Cardiac involvement generally correlates with poor prognosis, and treatment options are limited if presented late. Novel disease-modifying agents are being studied in on-going trials to optimize treatment strategy. This review aims to summarize the updates on upcoming treatment options for AL amyloidosis, particularly involving the heart. Methodology: We performed a comprehensive literature search on PubMed, clinicaltrials.gov, and Cochrane databases (last updated on May 20, 2020). We used MeSH terms along with their keywords and combined their results. The literature search generated a total of 652 references. Two independent reviewers screened the articles and shortlisted 21 clinical trials that were included in our final review. Results: Monoclonal antibodies (daratumumab, isatuximab, elotuzumab and birtamimab) are being studied as monotherapy and combinations in relapsed/refractory (RR) AL amyloidosis. Despite good data on efficacy and safety, Daratumumab has not been approved yet in this category for advanced cardiac amyloidosis patients. Isatuximab showed the overall hematological response (HR) of 56% in phase I trial in a combination regimen and is now being evaluated as monotherapy in phase II. In a recent phase III trial of RR AL amyloidosis patients, the median progression-free survival was assessed over 24.5 months. It was increased from 14.9 months (lenalidomide and dexamethasone alone) to 19.4 months (elotuzumab, lenalidomide, and dexamethasone). Immunomodulators (lenalidomide, pomalidomide, thalidomide) are well studied for safety in other malignancies. Lenalidomide in various combinations has shown hematological response of greater than 60% in AL amyloidosis. Similarly, pomalidomide has shown an overall hematological response of 48-50% in two different early phase trials. Moreover, thalidomide was associated with significant toxicity in phase I/II trials and was discontinued. Second-generation proteasome inhibitors (ixazomib and carfilzomib) were assessed in RR cases of AL amyloidosis. Ixazomib achieved a hematological response of 52%. However, carfilzomib has been associated with cardiovascular toxicity and a higher risk of hospitalization in phase I trials, making it unsuitable. Venetoclax has shown encouraging results in multiple myeloma, particularly in t(11:14). 50% of AL amyloidosis cases have t(11:14) in whom venetoclax can be beneficial. A trial [NCT03000660] was suspended halfway citing clinical hold from regulatory authorities. Alkylating agents, mainly bendamustine, are currently under study after it showed a survival advantage in heavily pretreated cases [NCT01222260]. Underexplored venues: Small interfering RNAs (siRNAs) have a favorable response and excellent toxicity profile in AL amyloidosis. Issues regarding half-life and delivery systems have limited their use. CAEL-101, a novel chimeric fibril-reactive monoclonal antibody (gG1κ 11-1F4), tolerated well with improved organ function in AL amyloidosis in an early phase trial where it improved global longitudinal strain from baseline -9.58 to -13.39. SB203580 + rapamycin combination works in synergy with the former inhibiting the p38 MAPK pathway markedly reducing the toxicity of light chain immunoglobulins on cardiac myocytes and the latter restoring the SB203580-induced autophagic dysregulation. Epigallocatechin-3-gallate (EGCG) was well tolerated and found non-inferior to standard chemotherapy in a small phase II trial [NCT01511263]. Serum amyloid P (SAP) is a chaperone protein in amyloid fibril formation. Anti-SAP antibodies have shown promising results with safe toxicity profile in phase I trial [NCT01777243] in non-cardiac involved patients. However, another trial in cardiac involved cases was terminated due to significant toxicity. Table 1 Conclusion: Numerous drugs with novel mechanisms of actions are being studied, and results so far offer hope for improving the therapy & outcomes, especially in patients with cardiac involvement. The drug combination regimens lead to slow down the disease progression by interfering at multiple steps in the cascade of light chain synthesis, secretion, deposition, and organ clearance. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Introduction: Blinatumomab is a bispecific T-cell engaging antibody that binds and allows CD3 cytotoxic T cells to recognize and eradicate CD-19 positive malignant B cells. Blinatumomab is currently under study for relapsed and refractory B-cell acute lymphoblastic leukemia (RR B-ALL). Methods: A comprehensive literature search was conducted across various data sets, including PubMed, Cochrane, and Embase, and presented data in ASH and ASCO. A review of the most recent data is summarized in this abstract. Results: Eight clinical trials are currently under various phases of the study evaluating blinatumomab in RR B-ALL. In the phase 1/2 trial by Locatelli et al., 110 patients treated with blinatumomab showed complete remission (CR) with In a phase II study, Martinelli et al., treated 45 patients at a dose of 9 µg/day in week 1, f/b 28 µg/day; 36% of the patients achieved CR. In another phase II trial by Gokbuget et al., a 15 µg/day dose in 20 patients resulted CR in 50% pts. Topp et al. reported CR of 43% in 39 patients, and Stein et al. reported 45% CR in 64 patients treated with a similar regimen. In phase III trials, Rambaldi et al., reported 36% CR in 119 patients and, Kantarjian et al. reported CR of 43.9% in 271 patients treated with blinatumomab at a dose of 9 µg/day during week 1 and 28 µg/d onwards for up to 3 and 6 cycles, respectively. In all the trials, blinatumomab was given via 4-week continuous IV infusion followed by 2-week treatment-free interval per cycle. The most common grade 3 and 4 adverse effects are listed in the table 1. Conclusion: Blinatumomab is showing promising results in RR B-ALL with a good side effect profile. However, the final results of these trials are awaited. Figure 1 Figure 1. Disclosures Anwer: Janssen pharmaceutical: Honoraria, Research Funding; Allogene Therapeutics: Research Funding; BMS / Celgene: Honoraria, Research Funding; GlaxoSmithKline: Research Funding.

Background and Objective: Disease relapse remains the primary cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (Allo-HSCT) in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Oral azacitidine (5-aza) was associated with clinical benefit as maintenance therapy in transplant ineligible patients. However, contradicting data have been reported regarding the role of 5-aza as a maintenance therapy to reduce relapse rate -post-allo-HSCT. We conducted this systematic review to describe the efficacy and safety of 5-aza in this context. Materials and Methods: We systematically searched multiple databases, including PubMed, Embase, Cochrane, and Clinicaltrials.gov. We also searched major conferences for oral or poster presentations. We used MeSH terms and keywords for MDS, AML, Allo-HSCT, and 5-aza. We included all retrospective and prospective studies of 5-aza (all formulations) published until March 2020. The primary database search yielded 1209 articles. We excluded irrelevant, duplicate, and review articles. The final search revealed 20 articles that we explored in detail for various efficacy and safety outcomes. Results: A total of 1211 patients were enrolled in 14 prospective and 6 retrospective studies. Of those, 1169 patients were evaluable. Prospective studies CALGB 100801 trial by Vij et al. (2015) reported overall survival (OS) of 45.7% and progression-free survival (PFS) of 41.2% at 24 months following reduced intensity conditioning (RIC) in a phase 2 trial of 41 patients. In a randomized control trial, Oran et al. (2018) evaluated relapse-free survival (RFS) as the primary outcome after 12 cycles of 5-aza at 32 mg/m2/day (n=187). Only 30% of the patients in the azacitidine arm completed the targeted number of cycles. The study showed a median RFS of 24.8 months in the treatment arm vs 15.3 months in the control arm (p=0.43). In a phase 2 trial conducted by Guillaume, T et al. (2019) the cumulative incidence of relapse was 27.6% in patients who received 5-aza, compared with 41.9% in 58 matched patients control group (p=0.21). Platzbecker et al. (2018-2019) studied a higher dose of azacitidine (75mg/m2/day) in a phase 2 trial as a pre-emptive strategy for patients who develop minimal residual disease (MRD) within 24 months. The 12-month OS and PFS were 94% and 44%, respectively. De Lima et al. (2018) studied the role of maintenance Oral 5-aza in Phase I/II trial (n=30). A dose-escalation design was used with a dosage ranging from 150 mg to 400 mg, received in a 7- or 14-day cycles. The 12-month PFS was 54% and 72% and estimated survival was 86% and 81% among 7-days and 14-days cycles, respectively. (Table 1) Retrospective studies: Mishra et al. (2017) reported a better OS in 14 patients who received 5-aza maintenance compared with a control arm (p-value 0.026). Cheikh et al. reported a 12-month OS of 70%. Ali, N et al. (2020) (n=107) compared 5-aza group vs. control group retrospectively. EFS was 53.1% vs. 49.5% (p=0.02) while OS was 56.8 and 53.4 months (p=0.01) in the treatment arm vs the control arm respectively. Safety: The most common grade 3 or 4 hematological adverse effect was neutropenia, while some patients also experienced grade 3 or 4 anemia, thrombocytopenia, or lymphopenia. The main non-hematological adverse effects were infections, fatigue, and gastrointestinal distress. The incidence of acute graft versus host disease varied from 13% to 50%. The most common reason for treatment discontinuation was disease relapse. A minority of patients discontinued treatment due to side effects. Conclusion: To our knowledge, this is the first comprehensive systematic review for the role of 5-aza maintenance -post-Allo-HSCT in patients with MDS or AML. The heterogeneity of the studies, in terms of dosing regimens, variable duration of treatment and patient selection, precludes definitive conclusions. Despite that, 5-aza seems to improve relapse rates and OS at least numerically but also significantly in some studies, as illustrated in this review. Low number of patients involved in most of these studies contributed to non-significant p-values. Azacitidine remains a valid and safe option, especially in patients with high risk of relapse. Further studies aiming at those high risk patients, such as AML with myelodysplasia related changes (AML-MRC) and high-risk MDS following RIC, are of utmost need. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Fazal:Takeda: Consultancy, Speakers Bureau; GlaxoSmithKline: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Speakers Bureau; Janssen: Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Incyte: Honoraria, Speakers Bureau; Karyopharm: Speakers Bureau; Jazz: Consultancy, Speakers Bureau.

Background: Amyloidosis is characterized by the deposition of misfolded lambda or kappa light chain (AL) proteins in tissue. It commonly affects the heart, which correlates with poor prognosis. Disease-modifying therapies aim to suppress the production of abnormal light chains. Daratumumab (Dara) use is associated with a reduction in light chain protein production. Dara is a human anti-CD38 monoclonal antibody approved for the treatment of newly diagnosed and Relapsed & Refractory Multiple Myeloma. AL amyloidosis plasma cells express CD38, and therefore, Dara is an attractive alternative in this setting. This review aims to assess the efficacy and safety of daratumumab in pre-treated AL amyloidosis patients. Methods: We conducted a comprehensive literature search in PubMed, Embase, Medline using MeSH terms and keywords "AL amyloidosis," "daratumumab", and "darzalex" to incorporate the studies published up to July 2020. We included studies assessing the efficacy and safety of daratumumab alone or in combination with other therapies in pretreated AL amyloidosis. After excluding duplicates, non-relevant, and review articles, we selected four prospective and twelve retrospective studies. RESULTS: In our review, data on 482 patients were included. The ages ranged from 35-88 years. The median number of prior therapies was 3 (ranges:2-6), and the most common therapy was bortezomib in 90% of patients followed by immunomodulators in 55% and stem cell transplant in 35%. A total of 260 (54%) patients received Dara monotherapy, 126 (26%) received Dara plus Dexamethasone (d), and 96 (20%) patients received other Dara containing two or three-drug regimens. The time from the diagnosis to the start of Dara therapy varied from 1 to 137 months. 71 % of patients had cardiac, and 62 % had renal involvement. There was a greater than 30 % reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) in cardiac patients responsive to therapy. 1. Daratumumab monotherapy: Dara monotherapy achieved an overall response rate (ORR) of 76% (191/249), complete response (CR) of 30% (69/224), very good partial response (VGPR) of 41% (79/192) and partial response (PR) of 14% (19/140). The overall survival (OS) ranges from 59-100% at 10-12 months were noted. Table 1. 2. Daratumumab+ Dexamethasone: Dara plus d achieved ORR of 81% (86/106), CR of 51% (53/102), VGPR of 29% (18/62), PR of 15% (15/102), and OS of 87% at 24 months. Table 1. 3. Daratumumab with combination regimens: The use of Dara based combination regimens of Dara+pomalidomide (P)+d (36% of patients), Dara+lenalidomide (R)+d (32%) and Dara+bortezomib (V)+d (18%), reported by Abeykoon et al., showed an ORR of 88% (14/16), CR of 19 % (3/16), VGPR of 63% (10/16), PR of 6 %(1/16), OS of 89 % at 10 months and progression-free survival (PFS) of 83% at 10 months. Godara et al. reported an ORR of 100% (9/9) using a combination of Dara and birtamimab. The combination of D+cyclophosphamide (c)+V+d reported by Palladini et al. achieved an ORR of 96 % (27/28), CR of 36 % (11/28), VGPR of 29 % (8/28) and PR of 14 % (4/28).Table 1. The most reported adverse event was infusion-related reactions; grade 3-4 adverse were less than 10 % and mostly related to the heart (heart failure & atrial fibrillation). The most-reported hematological adverse effects were anemia, thrombocytopenia, neutropenia, infections, and sepsis. The most common non-hematological adverse events were heart failure, bronchitis, pneumonia, fatigue, nausea, and diarrhea. Table 2. Conclusion: Dara therapy is associated with promising efficacy with a response rate of more than 70% when used alone and more than 80% when used in combination. These regimens are well tolerated in advanced cardiac disease patients with a tolerable risk of volume overload and infusion-related complications. Additional multicenter randomized, double-blind clinical trials are needed to confirm these results. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Introduction: Venous thromboembolism (VTE) is one of the major causes of mortality among patients with malignancy. It is estimated that around 4-20% of patients with cancer experience venous thrombosis. Typically, low molecular weight heparin (LMWH) is used as an initial agent of choice in VTE except in patients with renal insufficiency who cannot tolerate LMWH and require alternate therapy. Also, despite adequate therapy, VTE recurrence is common among cancer patients. The novel oral anticoagulants (NOACs) have recently been introduced in the treatment of VTE and have shown promising results. We have performed a systemic review of the literature comparing the safety and efficacy profiles of NOACs with LWMH in cancer patients with VTE. Methods: We performed a comprehensive literature search completed on July 7, 2020, on Pubmed, Cochrane library, and ClinicalTrials.gov. We used the MeSH terms: 'venous thrombosis', 'neoplasms', 'rivaroxaban', 'dabigatran', and 'enoxaparin' with associated entry terms. Our search yielded 46 studies. Following PRISMA guidelines and subsequent screening by three reviewers, we shortlisted 5 completed clinical trials (n=2873) and included data from these studies in our systemic review. Results: EINSTEIN-PE investigators (2013, n=223) reported a net clinical benefit (VTE plus major bleeding) in 83 patients (3.4%) vs 96 patients (4%) in the rivaroxaban arm versus control arm (enoxaparin + warfarin/acenocoumarol arm) respectively (HR 0.85 [95% CI 0.63-1.14], p=0.28). Recurrence occurred in 2.1% vs 1.8% (HR 1.12 [95% CI 0.75-1.68] p=0.003). Major bleed events occurred in 1.1% vs 2.2% (HR 0.49 [95% CI 0.31-0.79] p=0.003). Clinically relevant minor bleed events occurred in 9.5% vs 9.8%. Deaths were lower in rivaroxaban arm (20 vs 23). Hokusai-VTE investigators (2013, n=414) reported edoxaban as non-inferior to warfarin when compared the primary efficacy (defined as recurrence of symptomatic VTE) 3.2% vs 3.5% respectively (HR 0.89 [95% CI 0.70 to 1.13] p AMPLIFY study (2015, n=169) reported reduced recurrence rate of 3.7% vs 6.4% in apixaban vs conventional therapy (enoxaparin + warfarin) respectively (RR 0.56 [95% CI 0.13-2.37]). Major bleed events weremore common in controls 2.9% vs 5% (RR 0.45 [95% CI 0.08-2.46]). Non major bleed events occurred in 12.6% vs 22.5% (RR 0.57 [95% CI 0.29-1.12]). Three vs five deaths occurred in apixaban arm vs conventional therapy respectively. MAGELLAN study (2013, n=592) reported a better net clinical benefit (defined as primary efficacy outcome up to 10 days or safety outcome up to 35 days) of 9.4% vs 7.8% in rivaroxaban vs enoxaparin respectively. Recurrence was low in rivaroxaban (4.8% vs 6.4%). Major bleed events occurred more commonly in rivaroxaban arm 2.85% vs 0.95% (RR 2.9 [95% CI 1.60-5.15] p ADAM VTE (2020, n=300) reported recurrence in 0.7% vs 6.3% in apixaban vs dalteparin respectively (HR 0.099 [95% CI 0.013-0.78] p=0.0281). Major bleed events noted in 0 vs 1.4% (p=0.138) and clinically relevant non-major bleed events noted in 6.2% vs 4.2% patients in the apixaban vs control respectively. Deaths were more common in apixaban group 23 (16%) vs dalteparin group 15 (11%). Conclusion: NOACs have comparable efficacy to conventional LMWH based treatment options and are feasible alternate therapy for VTE in patients with cancer. Apixaban so far has demonstrated better efficacy profile among the NOACs. However, the data at present is conflicting regarding safety profile. Large double-blinded randomized clinical trials are required to confirm the safety profile. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

Background: Clonal plasma cells in multiple myeloma (MM) over express b-cell lymphoma-2 protein (BCL2). Which is the target for venetoclax (VEN). VEN has a promising efficacy and a favorable safety profile in MM patients. This review highlights the efficacy of VEN for the treatment of relapsed refractory (RR) MM. Methodology: We performed a comprehensive database search on four major databases(PubMed, Embase, Cochrane, and Clinical trials.gov). Our search strategy included MeSH terms and keywords for multiple myeloma and VEN, including trade names and generic names, from the date of inception of the database to April 2020.The initial search revealed 782 articles. After excluding review articles, duplicates, and non-relevant articles,we included six studies(four clinical trials and two retrospective studies), which reported an overall response rate (ORR) in RRMM patients. Proportions along with 95% Confidence Interval (CI) were extracted to compute pooled analysis using the 'meta' package by Schwarzer et al. in the R programming language (version 4.0.2) to report the efficacy of VEN. We pooled the results of the experimental arms of included trials using the inverse variance method and logit transformation. Between studies,the variance was calculated using Der Simonian-Laird Estimator. Results: We identified 568 patients from four clinical trials [Moreau et al.2019, the BELLINI trial, (n=291, venetoclax arm= 194, placebo arm= 97)], Costa et al. 2018 (n=42), Kumar et al. 2017(n=66), and Moreau et al. 2017 (n=66)] and two retrospective studies (Kambhampati et al. 2020 (n= 47) and Sidiqi et al.2019 (n=56)). Among which 563 patients were evaluable for the treatment outcomes. One hundred and forty two patients (25%) had t(11:14)mutation. The median age of the patients ranged from 64-66 years, and the median number of prior therapies was ≥2. The median dose of venetoclax ranged from 50 mg/day to 1200 mg/day in dose-escalation cohorts of clinical trials while in the retrospective study by Kambhampati, S et al., the median dose of venetoclax was 800 mg/day. The pooled overall response rate (ORR) for all patients who received venetoclax (n=466) was 57% (95% confidence interval (CI) 0.34-0.77, p Conclusion: VEN is an effective treatment option for relapsed and refractory multiple myeloma patients with t(11:14) translocation. The overall response rate and the duration of response are better in patients with t(11:14). The CANOVA trial is ongoing now to better answer the debatable question of VEN efficacy in t(11;14) MM patients. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Fazal:Jansen: Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Karyopham: Speakers Bureau; Celgene: Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau.