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Introduction Lenalidomide use in nearly all induction regimens for multiple myeloma (MM) has led to the treatment of lenalidomide-refractory disease becoming one of the most important clinical questions in its treatment. Given the lack of direct comparisons of treatment regimens for lenalidomide-refractory MM, we used a systematic review to identify randomized controlled trials (RCTs) that included lenalidomide-refractory subgroup analysis. Methods We performed a systematic review to identify RCTs for MM that enrolled patients with lenalidomide-refractory disease, then performed a network meta-analysis (NMA) using random effects model to compare regimens. Results We identified 123 discrete RCTs, of which 7 reported primary outcomes for lenalidomide-refractory MM. These were linked in 2 discrete networks totaling 1698 lenalidomide-refractory patients. Network 1 compared bortezomib (bort)/dexamethasone (dex) versus other treatments, and analysis showed triplet therapy with pomalidomide (pom)/bort/dex (hazard ratios [HR] 0.65, 95% confidence interval [CI], 0.50–0.84), daratumumab (dara)/bort/dex (HR 0.36, 95% CI, 0.21–0.63), and dara/carfilzomib (carf)/dex (HR 0.38, 95% CI, 0.21–0.69) as more effective than bort/dex. Network 2 compared dex versus other treatments, and analysis showed pom/dex (HR 0.50, 95% CI, 0.40–0.62), isatuximab (isa)/pom/dex (HR 0.30, 95% CI, 0.20–0.44), and elotuzumab (elo)/pom/dex (HR 0.27, 95% CI, 0.16–0.45) as more effective than dex. Within each network, monoclonal antibody (mAb)-containing regimens had lower HRs and higher P-scores than non-mAb regimens, indicating higher likelihood of these regimens being most efficacious. Conclusion The results of our NMA demonstrated that for lenalidomide-refractory MM, triplet therapy containing mAbs are superior. There is need for further RCTs to better ascertain the best standard of care for these patients.

Chronic kidney disease (CKD) increases the risk of venous thromboembolism (VTE) among affected patients. Vitamin K antagonists (VKA) and warfarin remains the main stay of its treatment. Due to novelty and unclear risk-to-benefit ratio of direct oral anti-coagulants (DOAC), they remain underutilized in preventing VTE among CKD patients. We aim to assess the efficacy and safety of DOACs and other oral anticoagulants in preventing recurrent VTE among high-risk population.We conducted a literature search using PubMed, Embase, Cochrane, Web of Science and Clinicaltrials.gov for randomized controlled trials (RCTs) comparing anti-coagulants like DOAC, LMWH or VKA or any oral anti-coagulant (OAC) (This includes VKAs and DOACs) with either placebo or another anti-coagulant. Two independent reviewers screened the retrieved articles and extracted data using a piloted data extraction sheet. The primary outcome of interest was number of recurrent VTE and other side effects among CKD patients receiving respective treatment. Secondary outcomes were risk of major, non-major and intra-cranial bleed.We retrieved 7244 titles on initial search, reviewed full text of 818 articles, and selected 10 phase III RCTS for quantitative meta-analysis. Out of 36,326 patients in these trials, only 10,840 (29.8%) were evaluable. We stratified patients into four categories based on severity of renal impairment using serum creatinine clearance (SCr) as the marker e.g. mild (50 -80) moderate (30 - ≤50) severe (30) and any level (from30 to80). There was no difference between DOACs vs VKA in decreasing the risk of recurrent VTE among patients with mild (RR:0.86, 95% CI:0.61-1.22, IDOACS and other anticoagulants (VKA and LMWH) showed no statistical difference in preventing recurrent VTEs among CKD patients but DOACs had significantly lower risk of major and non-major clinically relevant bleeding irrespective of the level of renal impairment compared to VKAs. There was no difference in risk of intra-cranial bleeding between DOACs and VKAs.

Background Thromboprophylaxis is routinely used with lenalidomide-based regimens in multiple myeloma because of a substantial risk of venous thromboembolism (VTE). However, little is known about the incidence of VTE with contemporary lenalidomide-based regimens. The objective of the current study was to estimate the incidence of VTE despite thromboprophylaxis with currently used lenalidomide-based regimens in patients with myeloma. Methods The Ovid MEDLINE, Embase, and Cochrane databases were queried from study inception to January 2019 for keywords to cover the following concepts: "lenalidomide," "venous thromboembolism," and "multiple myeloma." Phase 1, 2, and 3 clinical trials evaluating lenalidomide-based regimens with thromboprophylaxis were included. The pooled incidence rate of VTE was estimated using a random-effects model. Results The search generated 1372 citations, with 51 clinical trials and 9069 patients included for analysis. The most common thromboprophylaxis agents were aspirin, low-molecular-weight heparin or warfarin, administered either per risk-stratification or at investigators' discretion. The pooled incidence of VTE in trials of patients who had newly diagnosed and relapsed/refractory myeloma was 6.2% (95% CI, 5.4%-7.1%) over median treatment durations ranging from 2 to 34 cycles, which translated into 1.2 VTE events per 100 patient-cycles (95% CI, 0.9-1.7 VTE events per 100 patient-cycles). Among contemporary regimens, the risk of VTE was low with combined lenalidomide and low-dose dexamethasone (0.2 [95% CI, 0.1-0.6] events/100 patient-cycles) and lenalidomide maintenance (0.0 [95% CI, 0.0-0.7] events per 100 patient-cycles). VTE risk was higher with combined lenalidomide and low-dose dexamethasone plus proteasome inhibitors (1.3 [95% CI, 0.7-2.3] events per 100 patient-cycles). Conclusions Despite adequate thromboprophylaxis, lenalidomide-based regimens have a substantial risk of VTE in controlled clinical trial settings. Further studies are needed on new thromboprophylaxis strategies with regimens that have a high VTE risk.

Introduction: Which vascular endothelial growth factor receptor inhibitor (VEGFRi) is less cardiotoxic compared to others in same class is not well known. We compared cardiovascular safety profile of all FDA approved VEGFi used as chemotherapy for cancers. Methods: We performed PRISMA compliant literature search on PubMed, Embase, Cochrane, Web of Science, Scopus and Clinicaltrials.gov (inception-6/12/2021). Only phase 3 RCTs were included. Primary outcomes were hypertension (HTN), myocardial infarction (MI), heart failure (HF), conduction abnormalities, dyspnea and pedal edema. Random-effects meta-analysis (MA) was conducted followed by frequentist network meta-analysis (NMA). Results were reported as RR with 95% CI and OR with 95% credible intervals (CrI). Quality and risk of bias assessment were done using GRADE and Cochrane risk of bias assessment tools respectively. Results: This analysis included 20426 patients from 32 RCTs. There was a very high risk of HTN associated with VEGFi compared to placebo (RR: 4.36, 95% CI:3.5-5.4, I2:69%, p-value: Conclusions: VEGFi are associated with significantly higher risk of HTN compared to placebo. Among VEGFi, Lenvatinib is associated with slightly higher risk of HTN and there is no difference in risk of MI, HF, conduction abnormalities, dyspnea and pedal edema among VEGFi. Study is limited by heterogeneous patient population.

Introduction: Advancements in the treatment of multiple myeloma (MM) with proteasome inhibitors [bortezomib (bort), carfilzomib (carf)], monoclonal antibodies [daratumumab (dara), isatuximab (isa) and elotozumab (elo)], and immunomodulatory drugs [IMiD) [lenalidomide and pomalidomide (pom)] have improved outcomes. However, using lenalidomide as frontline treatment and maintenance therapy exposes greater numbers of patients to lenalidomide prior to relapse. Consequently, the treatment of lenalidomide-refractory (LR) disease is an increasing area of concern. Given the lack of direct comparisons of different treatment regimens for LR MM, we used a systematic review to identify randomized controlled trials (RCTs) that included subgroup analysis of LR patients. The objective of our study was to compare the efficacy of novel treatment regimens in randomized trials for patients with LR MM using a network meta-analysis. Methods: Three databases were searched: MEDLINE/PubMed, Embase, and Cochrane Registry of Controlled Trials. All studies published between January 1, 2005 and December 30, 2019 were queried using keywords "multiple myeloma" and "randomized controlled trial". Only RCT's were included. Primary outcome was progression free survival (PFS) of patients enrolled in myeloma RCT's. Two independent investigators reviewed all the studies and resolved any conflict through mutual discussion. WNetwork meta-analysis using random-effects model was performed to generate direct and indirect comparisons between various treatment groups. Frequentist method was used to rank the interventions and P-score was generated. A higher P score (close to 1.00) corresponded to superior progression free survival. A P-value of 50% considered as significant heterogeneity. We used 'R' (Bell Labs, Murray Hill, NJ, USA) for generating our statistical analysis and plots. Results: Our initial search strategy yielded 1171 results. After excluding duplicates, trials in progress, subset analysis and non-randomized studies, 123 RCTs were identified. Only 8 studies clearly reported outcomes of patients with LR myeloma and 7 studies (1698 patients) were included in final analysis of two discrete networks. Pom/bort/dex (HR: 0.65,95% CI: 0.50-0.84), dara/bort/dex (HR: 0.36, 95% CI: 0.21-0.63), and dara/carf/dex (HR: 0.38, 95% CI: 0.21-0.69) were all found to have improved PFS compared to bort/dex (Figure 2). These interventions were ranked as follows: Dara-bort-dex was the most efficacious with a P-score of 0.8758, followed by Dara/carf/Dex (P of 0.8514), Pom/bort/dex (P of 0.4791), Carf/dex (P of 0.2707) and Bort/dex (P of 0.0231). Within Network 2 (Figure 3), pom/dex (HR :0.50, 95% CI= 0.40-0.62), isa/pom/dex (HR: 0.30, 95% CI= 0.20-0.44) and elo/pom/dex (HR: 0.27, 95% CI=0.16-0.45), were all found to have improved PFS compared to dexamethasone (Figure 4). In Network 2, the ranking of interventions was as follows with Elo-pom-dex (P of 0.8716) the most efficacious, followed by Isa-pom-Dex (P of 0.7932) and Pom-dex (P of 0.3352). Conclusion: The results of our network meta-analysis of 1698 patients with lenalidomide refractory myeloma enrolled in seven randomized myeloma trials demonstrate that for lenalidomide refractory myeloma, triplet therapy is superior to doublet therapy. Regimens with the highest efficacy in this subset of patients were triplets containing monoclonal antibodies (such as dara/elo/isa). There is a need for further randomized data to better ascertain the best standard of care for these patients. Disclosures No relevant conflicts of interest to declare.

Objective To perform a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating risk-benefit for adjuvant postoperative treatments in high-risk renal cell carcinoma by assessing reported disease-free survival (DFS), overall survival (OS), toxicity, and quality of life. Methods A literature search was performed in PubMed, Embase, Web of Science, and Cochrane Central Register of Controlled Trials to identify relevant RCTs (from database inception through May 15, 2018). The results of the ATLAS trial were published while writing this manuscript, and the manuscript was updated accordingly. A generic variance-weighted random effects model was used to derive estimates for efficacy and common adverse effects. Heterogeneity was assessed using the Cochran Q statistic and was quantified using the I2 test. Results Adjuvant therapy with tyrosine kinase inhibitors compared with placebo was observed to have a DFS hazard ratio [HR] of 0.92 (95% CI, 0.83-1.01) and an OS HR of 1.01 (95% CI, 0.89-1.15) (4 RCTs; 4417 patients). Analysis of DFS for sunitinib compared with placebo (n=1909) in the adjuvant setting detected an HR of 0.90 (95% CI, 0.67-1.19). Increased risk of grade 3 or 4 adverse events (relative risk [RR]=2.6; 95% CI, 2.28-2.97), diarrhea (RR=9.89; 95% CI, 4.22-23.14), fatigue (RR=3.11; 95% CI, 1.86-5.18), hypertension (RR=3.63; 95% CI, 2.99-4.41), and palmar/plantar dysesthesia (RR=2.70; 95% CI, 2.47-2.96) was observed. Conclusion Adjuvant vascular endothelial growth factor tyrosine kinase inhibitors in high-risk renal cell carcinoma did not improve OS or DFS, and there was a significant increased risk of toxicity in greater than half of the patients, leading to a decline in quality of life.

Background: Poly (ADP-ribose) polymerases (PARPs) are a highly conserved family of enzymes whose main function is to preserve genomic integrity following DNA damage. PARP inhibitors (PARPi) are increasingly used in cancers with deficiencies in homologous recombination. Clinical trials in breast and ovarian cancers have led to several FDA approvals in recent years, and their use in clinical practice is continuing to rise. It is thus necessary to assess their adverse event (AE) profile. Method: Literature search was performed using Ovid MEDLINE, EMBASE, CENTRAL, and Scopus (inception through October 26, 2018). Eligible studies were phase 3, randomized, controlled trials that compared single agent PARPi to placebo or standard treatment. Number of patients treated and AEs reported were recorded. Observed incidence of AE was reported with 95% CI. Heterogeneity was evaluated using Cochran Q statistic and I2 statistics quantified the proportion of heterogeneity not due to chance. Results: Databases revealed 869 references. Of these, 6 were eligible: 2 in breast cancer (OlympiAD, EMBRACA) and 4 in ovarian cancer (NOVA, ARIEL3, SOLO1, SOLO2). PARPi included niraparib (NOVA), olaparib (OlympiAD, SOLO1, SOLO2), rucaparib (ARIEL3), and talazoparib (EMBRACA). Of 1,685 patients who received PARPi, incidence of any AE, regardless of grade, was 98.5% (95% CI, 97.2–99.2%). Common AEs were: nausea (incidence rate, 68.9% and 95% CI, 58.7%–77.5%), fatigue (56.3%, 45.3%–66.8%), anemia (46.3%, 37.2%–55.8%), vomiting (33.7%, 29.5%–38.3%), neutropenia (24.7%, 15.3%–37.4%), headache (23.9%, 19.9%–28.4%), and reduced appetite (21.7%, 19.3%–24.3%). Myeloid neoplasms were rare (1.2%, 0.7%–1.9%). Incidence of grade 3 or higher AE was 44.3% (30.2%–59.5%) and often related to myelosuppression, specifically anemia (24.7%, 15.3%–37.4%), neutropenia (10.7%, 6.6%–16.9%), and thrombocytopenia (5.0%, 1.7%–14.0%). Incidence of serious AE was 24.3% (19.4%–29.9%); dose interruption occurred in 53.3% (41.2%–65.0%) and dose reduction occurred in 39.2% (23.6%–57.4%). 10% (7.4%–13.6%) of patients discontinued therapy due to AE. Death due to AE was rare; less than 1% (0.4%, 0.2%–0.8%) in all trials. Conclusion: Myelosuppression and gastrointestinal toxicities were the most commonly reported AE in 6 randomized phase 3 trials of PARPi for breast and ovarian cancers. Therapy was rarely discontinued due to AE. It remains to be seen whether these results will be reflected in clinical practice.

Investigators are using checkpoint inhibitors (CPIs) to treat aggressive hematologic malignancies in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in some patients with relapsed disease after allo-HSCT. CTLA-4 inhibitors and PD-1 inhibitors are 2 main types of CPIs, which work through activation of the immune system. On one hand, CPIs can achieve graft-versus-tumor effect, and on the other hand, there is a risk of graft-versus-host disease (GVHD). After a comprehensive literature review, we included data (n = 283) from 24 studies (11 original manuscripts and 13 case reports or case series) and evaluated the results to assess the safety and efficacy of CPI use in conjunction with allo-HSCT. Among the 283 patients, 107 received CPI before allo-HSCT, and 176 received CPI after allo-HSCT. The most common indication for CPI use was for Hodgkin lymphoma. The CPIs used in various studies included ipilimumab, nivolumab, and pembrolizumab. Among the patients exposed to CPI before allo-HSCT, 56% developed acute GVHD and 29% developed chronic GVHD. Investigators reported 20 deaths, 60% of which were GVHD-related. The overall mortality risk with GVHD is 11%. In this group, investigators noted an objective response rate (ORR) in 68% of patients, with complete remission (CR) in 47%, partial remission (PR) in 21%, and stable disease in 11%. Among the patients who received a CPI after allo-HSCT for disease relapse, 14% developed acute GVHD and 9% developed chronic GVHD. Investigators reported 40 deaths, 28% of which were GVHD-related. The mortality risk with GVHD is approximately 7%. Investigators reported ORR in 54% of patients, with CR in 33%, PR in 21%, and disease stabilization in 5%. After careful evaluation of collective data, we found that CPI use both before and after allo-HSCT can be highly effective, but exposure can lead to a significantly increased risk of GVHD-related morbidity and mortality in this patient population. Despite limited availability of data, there is need for extreme caution while making decisions regarding the use of CPIs. Detailed discussions and prospective well-designed clinical trials are needed to explore this issue further.

Ibrutinib has shown to have better efficacy than standard chemoimmunotherapy in del17 positive chronic lymphocytic leukemia (CLL) patients; however its role in del17 negative patients is less clear. We aim to evaluate the efficacy of ibrutinib-based regimens in CLL. Seven databases were searched in accordance with PRISMA statement guidelines using the following keywords: chronic lymphocytic leukemia, CLL, Bruton tyrosine kinase inhibitor, BTK inhibitor, ibrutinib, and PCI-32765. Data from only prospective clinical trials was included. In a phase 3 trial (n = 136), the overall response rate (ORR) with ibrutinib was 92% whereas 18% patients had a complete response (CR). Progression free survival (PFS) and overall survival (OS) at 2 years were 89% and 95% respectively. Phase 3 trial (n = 195) with single agent ibrutinib showed ORR of 63%. PFS at 6 months and OS at 12 months were 88% and 90% respectively. In a phase 2 trial of relapsed and/or refractory (R/R) or high risk treatment naive (TN) patients, combination of ibrutinib and rituximab (n = 104) achieved an ORR of 100% (CR 28%) as compared to ORR 98% (CR 21%) with ibrutinib monotherapy (n = 102) with no significant difference in PFS. Combination of ibrutinib and ublituximab (n = 64) had an ORR of 78% (CR 7%) in a phase 3 study. In del17p negative R/R patients, combination of bendamustine/rituximab (BR) and ibrutinib (n = 289) achieved an ORR of 83% (CR/CRi 10%) and the 18 month PFS was 79%. In a phase 2 trial treated with ibrutinib (n = 145), patients with del17p R/R disease achieved an ORR of 64% and the 24 month PFS and OS was 63% and 75% respectively. In TN del17p patients (n = 35), ORR was 97% (CR-0) and the 24 month PFS and OS were 82% and 84% respectively with single agent ibrutinib. Ibrutinib is the treatment of choice for patients with del17p mutation and has good efficacy in RR/TN patients without del17p mutation. Ibrutinib is being evaluated in combination with rituximab for del17p mutations. Future prospects include combination of ibrutinib with frontline chemotherapy and other novel agents for TN and RR del17p negative patients.

Background. Acute on chronic liver failure (ACLF) carries a poor prognosis unless liver transplantation is offered. We present risk factors associated with proceeding with liver transplantation in patients with ACLF. Methods. A retrospective review of all patients with ACLF who presented to a single transplant center between January 2016 and December 2017 was performed. We compared patients who were transplanted with patients who were not. Results. During the study period, 144 patients with ACLF were identified, 86 patients (59.7%) were transplanted, and 58 were not. The transplanted patients had a lower number of failed organs (4 versus 5, P < 0.001) and lower incidence of ACLF grade 3 (76.7% versus 94.8%, P = 0.014) compared with nontransplanted patients. Liver transplantation offered a 1-y survival of 86% as compared to 12% in the nontransplanted group. Hospital charges were significantly higher among transplanted patients as compared with the nontransplanted patients ($227 886 versus $88 900, P < 0.001). Elevated serum lactate was a risk factor in not offering liver transplantation in ACLF patients. Conclusions. In appropriately selected patients with ACLF, liver transplantation is feasible and can provide above 86% 1-y patient survival even in grade 3 ACLF.

Recent studies have raised concerns that fluoroquinolone use is associated with an increased risk of aortopathy, including aortic aneurysm with and without dissection.We performed a meta-analysis with a comprehensive literature review to further investigate this association.This analysis was conducted per PRISMA guidelines. PubMed, Cochrane Library, ClinicalTrials.gov, Embase, Web of Science, and Google Scholar were searched for studies that included adult patients (age18 years) exposed to fluoroquinolones or control antibiotics (amoxicillin/any other antibiotic) for urinary tract infection or pneumonia with a primary outcome of aortic aneurysm or dissection. Heterogeneity was calculated using Q statistic IA total of 6 studies-comprised of 59% males-were included in our analysis, which showed an increased combined risk of development of aortic aneurysm and aortic dissection with quinolone exposure when compared with controls (relative risk [RR] = 2.11; 95% CI, 1.62 - 2.75; ICompared to other antibiotics, the use of fluoroquinolones was associated with a significantly higher risk of aortic aneurysm and dissection combined.

BACKGROUND Thrombocytopenia (TP) is associated with higher incidence of bleeding in the setting of percutaneous coronary intervention (PCI) leading to increased morbidity and mortality. Herein, we report a meta-analysis evaluating the effects of baseline thrombocytopenia (bTP) on cardiovascular outcomes in patients undergoing PCI. METHODS Literature search was performed using PubMed, Embase, Cochrane library and clinicaltrials.gov from inception till October 2019. Patients were divided into two groups: Patients with (a) no Thrombocytopenia (nTP) (b) bTP before PCI. Primary endpoints were in-hospital, and all-cause mortality rates at the longest follow-up. The main summary estimate was random effects risk ratio (RR) with 95% confidence intervals (CIs). RESULTS A total of 6,51,543 patients from 10 retrospective studies were included. There was increased in-hospital all-cause mortality (RR 2.58 [1.7-3.8], p

Background: The ASPIRE and ENDEAVOUR trials have shown cardiovascular adverse effects in patients treated with carfilzomib-based regimens. Therefore, we conducted this meta- analysis of published clinical trials to identify the cumulative incidence and risk of cardiovascular adverse effects due to carfilzomib. Methods: A systematic search of PubMed, Embase, Web of Science, and Cochrane library was performed, and we identified 45 prospective trials of carfilzomib with data on 5583 patients. Among all patients being treated with carfilzomib (N=5,583), 8.9% sustained all grade cardiotoxicity, while 4.4% sustained high-grade cardiotoxicity. All-grade hypertension was present in 13.2%, while the incidence of high-grade hypertension was 5.3%. Result: The observed incidences of all-grade heart failure, edema, and ischemia were 5.1%, 20.7%, and 4.6%, respectively. Likewise, for high-grade heart failure and edema observed incidence was 3.2%, and 2.7%, respectively. There was no difference in the event rate of all and highgrade cardiotoxicity between newly diagnosed multiple myeloma and relapsed/refractory (p-value 0.42 and 0.86, respectively). Likewise, we did not observe any difference in the event rate of all and high-grade cardiotoxicity when carfilzomib was used as a single agent versus when used in combination therapy with other agents (p-value 0.43 and 0.73, respectively). Conclusion: Carfilzomib is associated with a significant risk of cardiovascular toxicity and hypertension. With the increasing utilization of carfilzomib, it is critical for primary care physicians, oncologists and cardiologists to be aware of the risk of cardiotoxicity associated with the use of carfilzomib to recognize and treat baseline cardiovascular risk factors in such patients.

Background Acquired thrombocytopenia (aTP) is associated with a high frequency of bleeding and ischemic complications in patients undergoing percutaneous coronary intervention (PCI). Herein, we report a meta-analysis evaluating the adverse effects of aTP on cardiovascular outcomes and mortality post-PCI. Methods A literature search was performed using PubMed, Embase, Cochrane and, clinicaltrials.gov from the inception of these databases through October 2019. Patients were divided into two groups: 1) No Thrombocytopenia (nTP) and 2) Acquired Thrombocytopenia (aTP) after PCI. Primary endpoints were in-hospital, 30-day and all-cause mortality rates at the longest follow-up. The main summary estimate was random effects Risk ratio (RR) with 95% confidence intervals (CIs). Results Seven studies involving 57,247 participants were included. There was significantly increased in-hospital all-cause mortality (HR 10.73 [6.82–16.88]), MACE (HR 2.96 [2.24–3.94]), major bleeding (HR 4.78 [3.54–6.47]), and target vessel revascularization (TVR) (HR 7.53 [2.8–20.2]), in the aTP group compared to the nTP group. Similarly, aTP group had a statistically significant increased incidence of 30-day all-cause mortality (HR 6.08), MACE (HR 2.77), post-PCI MI (HR 1.98), TVR (HR 5.2), and major bleeding (HR 12.73). Outcomes at longest follow-up showed increased incidence of all-cause mortality (HR 3.98 [1.53–10.33]) and MACE (HR 1.24 [0.99–1.54]) in aTP group, while there was no significant difference for post-PCI MI (HR 0.94 [0.37–2.39]) and TVR (HR 0.96 [0.69–1.32]) between both groups. Conclusions Acquired Thrombocytopenia after PCI is associated with increased morbidity, mortality, adverse bleeding events and the need for in-hospital and 30- day TVR.

Psoriasis is a chronic, immune-mediated disorder that affects approximately 7.5 million people in the United States. Individuals with psoriasis may develop cutaneous, articular, and systemic manifestations, which are a source of significant morbidity and a heightened risk of mortality, and may adversely impact patient-reported quality of life measures. Psoriasis is now recognized as a risk factor for cardiovascular disease, metabolic syndrome, peripheral vascular disease, inflammatory bowel disease, certain malignancies, and chronic renal disease. Therefore, it has become increasingly relevant that primary care physicians have a basic working knowledge and an understanding of fundamental management principles of psoriasis. This review highlights the salient clinical features of psoriasis and psoriatic spectrum disease, emphasizing key updates with respect to systemic disease and associated conditions, and briefly outlines a therapeutic algorithm for the primary care physician.

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are at a very high risk of hepatitis B virus reactivation (HBVr). Lamivudine is commonly used as prophylaxis against HBVr in high-risk patients undergoing allo-HSCT. Unfortunately, its efficacy is diminishing due to the development of HBV mutant drug-resistant strains. With the availability of newer antiviral agents such as entecavir, telbivudine, adefovir, and tenofovir, it is important to assess their role in HBVr prophylaxis. A comprehensive search of 7 databases was performed to evaluate efficacy of antiviral prophylaxis against HBVr in allo-HSCT patients (PubMed/Medline, Embase, Scopus, Cochrane Library, Web of Science, CINAHL, and ClinicalTrials.gov (June 21, 2017)). We identified 10 studies, with 2067 patients undergoing allo-HSCT; these primarily evaluated the use of lamivudine and entecavir as prophylaxis against HBVr in patients undergoing allo-HSCT because there were little or no data about adefovir, telbivudine, or tenofovir as prophylaxis in this specific patient population. Thus, included studies were categorized into 2 main prophylaxis groups: lamivudine and entecavir. Results of our meta-analysis suggest that entecavir is very effective against HBVr, although further clinical trials are required to test efficacy of new antivirals and explore the emerging threat of drug resistance.

Introduction Hematopoietic stem cell transplant (HSCT) is commonly performed for the treatment of advanced hematological malignancies. Emerging data suggest non-relapse related events, including cardiac arrhythmias, increasingly limit anticancer outcomes and non-relapse mortality after initially successful HSCT. Yet, the relationship between HSCT and increased risk of arrhythmias after transplant remains controversial and unclear. Our aim was to evaluate the incidence and effect on mortality risk of arrhythmia development after HSCT. Materials and methods Leveraging the PubMed, Embase, Cochrane, Scopus and Clinicaltrials.gov databases, we identified all published studies evaluating the incidence and impacts of early arrhythmias after HSCT from January 1995 to July 2021 using PRISMA guidelines. We included all available observational studies (case-control, and cohort) and clinical trials without restriction of language or country of publication. The primary outcome was incidence of atrial fibrillation (AF) at 1 year of follow-up after HSCT. Secondary outcomes included the incidence of any arrhythmia across follow-up, the incidence of left atrium (LA) dilation, and non-relapse mortality associated with HSCT induced AF. Subgroup analysis based on type of HSCT treatment employed, allogenic (Allo-HSCT) or autologous (Auto-HSCT), was also performed. Variance weighted random effects modeling (DerSimonian and Laird) was used to define the associations between HSCT and AF and mortality events. Outcomes were reported as event rates, and relative risks (RR). Medians were reported with corresponding standard errors (SE). Heterogeneity was assessed using Cochrane Q-statistic which was quantified with I 2test (>75% was considered high heterogeneity). Publication bias was assessed using Eager's test where applicable. Further, the quality of included studies was assessed using the New-Castle Ottawa scale. Results Overall, from 769 articles, 12 cohort studies inclusive of 6,371 patients meeting study-criteria were identified. The mean incidence of AF was 8.8% (I 2:97%, P Conclusion Atrial fibrillation is increasingly common after HSCT therapy, and associates with increased mortality. The presence of LA remodeling, reflected by atrial dilation, appears to portend AF risk. Further research into the mechanisms and predictors of AF after HSCT are needed. Figure 1 Figure 1. Disclosures Vasu: Kiadis, Inc.: Research Funding; Boehringer Ingelheim: Other: Travel support; Seattle Genetics: Other: travel support; Omeros, Inc.: Membership on an entity's Board of Directors or advisory committees. Saad: Incyte Pharmaceuticals: Consultancy; careDx: Consultancy; Amgen: Research Funding; Kadmon: Research Funding; OrcaBio: Research Funding; Magenta Therapeutics: Consultancy. de Lima: Miltenyi Biotec: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees. Jaglowski: Juno: Consultancy; Novartis: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding; Takeda: Consultancy; CRISPR Therapeutics: Consultancy.

Background: Patients diagnosed with thalassemia major who are transfusion dependant, have iron accumulation leading to iron toxicity and severe impairment in organs like heart, liver and endocrine organs which are highly sensitive to iron toxicity. This makes iron chelation therapy imperative for these patients. Half of the deaths resulting from iron toxicity related complications are attributed to cardiac complications. Iron chelation therapies have not been completely successful to prevent iron toxicity related complications like arrhythmia, cardiomyopathy and heart failure. Higher doses of iron chelation therapies have been associated with various side effects. Studies have shown L-type calcium channel blocker might be able to reduce iron uptake by myocardium. The aim of this meta-analysis is to assess the efficacy and safety of amlodipine to reduce myocardial iron concentration (MIC). Methods: We used PICO framework to do a systematic literature search using four database PubMed, Cochrane, Embase, and Web of Science using keywords, "Thalassemia" AND "Amlodipine" from the inception till July 2020. The initial search showed 90 articles out of which, six randomized clinical trials (RCT) (N= 226) were selected after exclusion of case reports, case series, preclinical trials, review articles, meta-analysis, and trials not providing any information about preventing iron overload in patients with transfusion dependent thalassemia. We extracted the data for myocardial iron concentration (MIC), myocardial T2, ferritin, hepatic iron/liver iron concentration (LIC), liver T2, left ventricular ejection fraction, response rate and adverse effects. DerSimonian-Laird random effects model was used to derive mean differences along with their 95% confidence interval (CI) using comprehensive meta-analysis version 3.0. Results: In six RCT, 96 patients were tested in experimental group and 97 in control group. In five RCT total number of male participants were 45 in experimental group and 54 in control group. 33 patients had splenectomy in experimental group and 41 in control group. The age range was 8 years to 31 years. The myocardial T2 score increased in amlodipine group compared to standard chelation group with significant mean difference estimated to be -0.62 (95% CI: -0.95-0.29, p-value: Conclusion: This systematic review and meta-analysis suggests that addition of amlodipine 2.5-5 mg/day to standard chelation therapy with monitoring for potential adverse effects, could benefit patients with thalassemia major by reducing cardiac iron overload and thus improve survival and quality of life. Future studies are required to study the role of amlodipine in reducing iron overload in endocrine organs that also absorb iron through voltage-gated channels, particularly considering the close association of cardiac siderosis with endocrine complications and the correlation of pancreas and MICs. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Sump syndrome is a rare, long-term complication with a prevalence ranging from 0% to 9.6% in patients with a history of side-to-side choledochoduodenostomy. Choledochoduodenostomy was originally performed to achieve drainage of the common bile duct in high-risk patients with low morbidity, which was commonly done in the pre-endoscopic retrograde cholangiopancreatography era. "Sump" comes from the segment of the common bile duct between the anastomosis and the ampulla of Vater, which acts as a stagnant reservoir for debris, stones, and static bile. This predisposes patients to changes in the biliary tree with signs and symptoms in relation to that area. If left untreated, cholangitis, pancreatitis, hepatic abscesses, and secondary biliary cirrhosis can develop. Here, we have a case of a 77-year-old male with a history significant for choledochoduodenostomy, who presented with the clinical signs and symptoms of pancreatitis, choledocholithiasis, and urinary tract infection. Computed tomography (CT) scan findings revealed choledocholithiasis and an enlarged common bile duct with smaller adjacent calculi along with pneumobilia consistent with sump syndrome. The patient's clinical status improved without invasive measures being taken, i.e. endoscopic retrograde cholangiopancreatography. He was subsequently discharged home after improving clinically and no invasive measures were pursued.

Objective: To determine the frequency of hepatitis B and C in patients undergoing elective cataract surgery. Study design: A descriptive study. Place of study: Ophthalmology Department, Teaching Hospital Dera Ghazi Khan. Duration of study: From 1st February 2017 to 30th September 2017. Methodology: All patients admitted for elective cataract surgery were included in the study. Screening was done for hepatitis B and C and findings were recorded. Hepatitis positive cases were identified and demographic data was collected on structured compilation sheets and analysis done. Results: A total of 889 patients were included in study. Overall, 52(5.85%) cases were positive for viral hepatitis B and C infection. 18(2.03%) were positive for hepatitis B and 34(3.82%) were positive for hepatitis C. 24 out of 52 cases (46.15%) were from rural areas and 28 out of 52 cases (53.85%) were from urban population. Conclusion: A significant number of hepatitis B and C positive cases were seen in patients admitted for elective cataract surgery. It is highly recommended that screening of preoperative cases of cataract surgery should be done so that even asymptomatic patients should pose no more threat to the spread of the disease. Key Words: Hepatitis B, Hepatitis C, Cataract surgery.

Extramedullary plasmacytoma is a type of plasma cell dyscrasia that can present as solitary tumor or secondary to multiple myeloma. We experienced a case of intramuscular plasmacytoma in the left thigh muscles of a patient secondary to multiple myeloma. A 73-year-old male with relapsed multiple myeloma and bilateral hip arthroplasty complained of lxeft lower limb weakness and hip pain 3 months after relapse. He underwent contrast-enhanced magnetic resonance imaging of lumbar spine and hip which was inconclusive. Subsequently, patient had multiple admissions for progressive lower limb weakness. His clinical course was complicated by a biopsy-proven plasmacytoma of the neck. He received localized radiation therapy to the neck in addition to a change in multiple myeloma chemotherapy regimen, resulting in resolution of the neck mass but his left lower extremity weakness continued to worsen. Repeat magnetic resonance imaging of hip and spine revealed an intramuscular mass in left thigh which was consistent with the diagnosis of extramedullary plasmacytoma on biopsy. Localized radiation to the thigh accompanied with a change in chemotherapy improved his symptoms and a significant reduction in size of plasmacytoma was observed. When an unexplained lower limb weakness is encountered with a history of multiple myeloma, secondary intramuscular plasmacytoma should be considered.

Blinatumomab and donor lymphocyte infusion (DLI) combination is a promising cancer therapy, whereby blinatumomab might achieve an initial reduction in leukemic-cell burden using T cells, and after tumor clearance, DLI can potentially stimulate the donor immune system to achieve longer lasting remission. Here, we present a 51-year-old female with mixed phenotype acute leukemia who had a hematologic relapse 3 months after she received total body irradiation-based myeloablative allogeneic hematopoietic stem cell transplantation from an unrelated human leukocyte antigen matched (10/10) donor and achieved complete remission with minimal residual disease negativity by multi-parameter flow cytometry using the combination of blinatumomab and DLI. To the best of our knowledge, this is the first report to describe the use of blinatumomab and DLI combination therapy in the treatment of B/myeloid mixed phenotype acute leukemia.

Clostridium ventriculi is a rare infection in poorly controlled diabetic patients with a history of gastroparesis. We present the first documented case in a transplant recipient, who underwent a simultaneous liver kidney transplant. Computed tomography showed emphysematous gastritis, endoscopy revealed gastric necrosis, and microscopy confirmed the diagnosis. Operative intervention was high risk, given the previous liver transplant. Antibiotics and proton pump inhibitor treatment with repeat endoscopy at 4 days showed resolution of gastric necrosis and elimination of microscopic evidence of infection. Combination antibiotic and proton pump inhibitor therapy may be an effective treatment for this rare, life-threatening infection.

Introduction: During recent years there has been a boom in the availability of treatments for multiple myeloma (MM). Based on the status of disease (newly diagnosed or relapsed/refractory), several regimens have successfully improved progression free survival (PFS) and overall survival (OS) in these two types of patients. Triple drug regimen is considered the current standard of care for newly diagnosed MM patients. However, with the advent of four drug regimens, some studies demonstrated a significant improvement in PFS and OS compared to standard of care where as others showed marginal to no difference. Also, it remains unclear whether the benefits of using four drug regimen outweigh the risks. Thus, the aim of our meta-analysis was to compare the efficacy and safety of four drug versus three drug regimens among newly diagnosed multiple myeloma patients. Methods: We built a PICO based search strategy using keywords like "multiple myeloma", "randomized clinical trials" and ran literature search on PubMed, Embase, Wiley Cochrane Library, Web of Science and ClinicalTrials.gov ranging from the date of inception till 16th July, 2020. A pre-validated data extraction sheet was used to extract data on PFS, OS and ≥Grade 3 hematologic adverse events at the longest follow-up. We included only randomized clinical trials (RCTs) comparing four versus three drug regimen in newly diagnosed MM patients. We excluded studies other than RCTs, studies conducted on relapsed refractory MM patients or other plasma cell dyscrasias. A generic variance weighted random effects model (DerSimonian and Laird) was used to derive hazard ratio estimates along with their 95% confidence intervals (CIs) for PFS and OS. Risk ratio along with its 95% CIs was estimated for Grade ≥3 hematologic adverse events. Heterogeneity was assessed with Cochrane Q -statistic and was quantified with I2 test (I2 >50% was consistent with a high degree of heterogeneity). A pre-specified sensitivity analysis was also performed for risk of adverse events. Cochrane Collaboration's tool was used to assess the quality of included RCTs and GRADE was used to rate the quality of evidence. Results: Initial search retrieved 7622 titles. After duplicate removal, 4880 articles were left. Following initial screening, 58 articles were considered for full text review. Of these only 3 studies (n=2277) met inclusion criteria. Four drug regimens included daratumumab, bortezomib, melphalan-prednisone (D-VMP), daratumumab, bortezomib, thalidomide-dexamethasone (D-VTd) and bortezomib and melphalan prednisone and thalidomide (VMPT-VT) respectively. Whereas, three drug regimens were bortezomib, melphalan-prednisone (VMP), bortezomib, thalidomide-dexamethasone (VTd) and bortezomib, melphalan and prednisone (VMP) respectively. There was a significant improvement in PFS when 4 vs 3 drug regimens were compared in patients with newly diagnosed MM (HR: 0.53, 95% CI: 0.46-0.62, p-value: Conclusion: Using four drug regimens, compared to three drug regimens, significantly improves PFS and OS among newly diagnosed multiple myeloma patients without any difference in the risk of ≥3 grade hematologic adverse events. Further randomized clinical trials are required to establish four drug regimen as standard of care for patients with newly diagnosed multiple myeloma. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Acquired thrombocytopenia after PCI is associated with a high frequency of bleeding and ischemic events. We conducted a metanalysis to evaluate the effect of acquired thrombocytopenia on in hospital and 30 day cardiovascular outcomes in patients undergoing PCI Literature search was performed using

Contrast induced Nephropathy (CIN) has been associated with morbidity and mortality. Oxidative stress play a major role in development of CIN. Increased Red cell Distribution Width(RDW) has been associated with an inflammatory state and poor outcomes in coronary artery disease (CAD) patients.

Lenalidomide is commonly used as induction or maintenance therapy in multiple myeloma. We report a case of 71-year-old female presenting with tardive dyskinesia-like symptoms one month after starting her lenalidomide maintenance therapy after high-dose chemotherapy and autologous hematopoietic stem cell rescue. Her symptoms evolved over days to pronounced uncontrollable limb movements, tongue smacking, lip-smacking, abnormal sounds, and tongue biting. The patient categorically denied any exposure to other drugs which are known to cause symptoms of tardive dyskinesia. The patient underwent a thorough evaluation, stopped the lenalidomide, and received therapy to control her symptoms with a gradual improvement over a six-week period. There is a paucity of literature on the association of lenalidomide with tardive dyskinesia. Common central nervous system-related side effects include peripheral neuropathy, dizziness, dysgeusia, headache, tremor, somnolence, and memory impairment. Very few studies in the existing literature have reported an association of tardive dyskinesia with lenalidomide therapy. Here, we present a case of an elderly female with multiple myeloma who developed severe tardive dyskinesia while she was on lenalidomide maintenance therapy.

R-CHOP has been the standard of care for diffuse large B cell lymphoma (DLBCL), curing approximately 60% of patients for more than 2 decades. However, the optimal treatment of patients who are too frail to tolerate this regimen and/or are not candidates for anthracycline therapy continues to be debated. MInT and GELA trials established addition of rituximab to CHOP in DLBCL but excluded patients older than 80 years. Multiple regimens have been tried with varying success in the very elderly, including R-mini-CHOP, R-mini CEOP, R-split CHOP, pre-phase strategies, and R-GCVP. However, there has not been a randomized trial among these strategies. Although addition of novel agents including ibrutinib, brentuximab vedotin, lenalidomide, and many others on the horizon holds promise in this population, none have been tested in a randomized setting or have results awaited. There is also a lack of a validated and easy to use clinical tool in this population to predict patients who will not tolerate R-CHOP. Identifying patients who will not tolerate R-CHOP early with the help of tools like CGA, along with integrating biology-based treatment (ibrutinib, lenalidomide in activated B cell type DLBCL) is being investigated in this population.

Background: Despite cancer being the second most common cause of death in the United States, more people are living longer after the diagnosis of cancer than before. Healthcare workers will be treating an increasing number of patients with cancer. Various studies have identified predictors of cardiac arrest in the general population, however, none have been done to identify such factors in cancer patients who form a more vulnerable group with lower survival rate following cardiac arrest. Methods: We retrospectively analysed charts of all patients with active cancer who experienced in-hospital cardiac arrest (IHCA) and underwent cardio-pulmonary resuscitation (CPR) from January 2015 to December 2017 at our hospital (n=44, group A). We compared this group to 44 consecutive patients with active cancer admitted to the oncology unit who did not experience cardiac arrest (n=44, group B). We excluded patients in remission. Results: Both the groups were comparable in terms of age (69 ± 14 vs 68 ± 15, p=0.776) and gender distribution (50% vs 56% males, p=0.521). Prevalence of coronary artery disease (CAD) (25% vs 11%, p=0.097), hypertension (68% vs 66%, p=0.821), hyperlipidaemia (34% in both groups, p=1.000), tobacco abuse (18% vs 27%, p=0.308), and diabetes mellitus (34% vs 23%, p=0.237) was not significantly different between the two groups. Group with cardiac arrest had significantly higher alanine aminotransferase (100 U/L ± 150 vs 47 U/L ± 87, p=0.043), alkaline phosphatase (288 U/L ± 512 vs 118 U/L ± 80, p=0.032), creatinine (1.8 mg/dl ± 1.74 vs 1.1 mg/dl ± 0.76, p=0.023), international normalised ratio (INR) (2.1 ± 1.5 vs 1.2 ± 0.5, p=0.005), and lower estimated -glomerular filtration rate (43 mL/min/1.73m2 ± 17 vs 51 mL/min/1.73m2 ± 15, p=0.022) on admission. Group A also had significantly higher incidence of sepsis during the hospital course as compared to group B (30% vs 2%, p

A 59-year-old male with a medical history of abdominal aortic dissection underwent a follow-up computed tomography (CT) scan abdomen, which showed an incidental pleural-based mass in the left lung base. The patient underwent an ultrasound (US)-guided biopsy and the histology was consistent with spindle cell carcinoma (SpCC). Staging workup was concerning for a metastatic lesion on the adrenal gland. The patient refused surgery and was subsequently started on chemotherapy. SpCC is a rare histological variant of sarcomatoid carcinoma. The prognosis is generally poor and treatment is the same as for other non-small cell lung cancers (NSCLC). The literature on disease progression and treatment is limited.

Multiple myeloma (MM) accounts for 1.6% of all cancers and 5%-10% of all hematologic malignancies in the United States (US). Despite marked progress in disease management, it remains incurable with high rates of relapse. We conducted a bibliographic analysis on the Web of Science (WOS) from July 25, 2017 and July 29, 2017. Among the top 100 most-cited articles (1901-2012), the most cited article received 2404 citations and least cited article received 336 citations. Forty-four of 100 articles were published in journals with impact factors greater than 20. We observed that over the years, the focus of research has shifted from diagnosis, staging, and pathogenesis to better treatment outcomes. A subgroup analysis of the top 100 cited articles published in the last five years (2012-2017) demonstrated that several landmark studies, which will likely change the landscape of treating multiple myeloma, were not included in the top 100 list. Interestingly, most of these articles were focused on novel therapeutic agents. This bibliographic analysis provides a list of the 100 top-cited articles in multiple myeloma along with the captivating comprehension of the history and development in various aspects of disease processes. The landscape of this disease is rapidly evolving, and bibliometric studies such as the one presented provide a valuable tool that can highlight the important transitions in the field.

Background The initial management of Acute bacterial skin and skin structure infection (ABSSSI) is burdensome. It requires empirical antibiotic therapy that covers both gram-positive and gram-negative bacteria. Vancomycin plus aztreonam are the most commonly used antibiotic combination, nonetheless, they have many limitations which limits their use. Hence, many new single agents with MRSA and gram-negative coverage, oral options, and/or good safety profile have been developed to be a potential alternative such as: ceftaroline, ceftobiprole, tigecycline and the recent FDA approved antibiotic (delafloxacin). In the absence of head-to-head trials comparing these agents, we decided to conduct a network meta-analysis for these therapeutic regimens. Methods A Bayesian network meta-analysis of randomized clinical trials identified in PubMed/Medline and Embase databases was conducted. We performed both fixed and random effect models for clinical cure as the primary outcome of interest. Additionally, rankograms were generated using the surface under the cumulative ranking curve (SUCRA) to obtain the treatment ranking probabilities in relation to their relative effect. Results We identified 10 eligible studies involving 4,914 patients. The indirect comparison demonstrated that delafloxacin showed no difference in terms of clinical cure compared with ceftaroline (OR, 0.82, 95% Cr.I 0.39–1.8), ceftobiprole (OR, 0.79, 95% Cr.I 0.32–1.9), SOC (OR, 1.2, 95% Cr.I 0.62–2.4) and tigecycline (OR, 1.0, 95% Cr.I 0.45–2.2) in the fixed effect analysis, nor in the random-effect analysis (OR, 0.8, 95% Cr.I 0.26–2.2; OR, 0.78, 95% Cr.I 0.2–3.0; OR, 1.2, 95% Cr.I 0.51–3.1; and OR, 0.96, 95% Cr.I 0.30–3.0), respectively. Furthermore, the ranking probabilities in the fixed-effect and random-effect analysis showed that ceftaroline was ranked the first in terms of clinical cure (SUCRA, 40.02%) followed by ceftobiprole (SUCRA, 22.80%), delafloxacin (SUCRA, 16.60%), SOC (SUCRA, 13.80%), and then tigecycline (SUCRA, 6.70%). Conclusion Ceftaroline, ceftbiprole, delafoxacin, SOC and tigecycline are similarly effective. However, delafloxacin provides better convenience. Further comparative studies regarding their safety are needed. Disclosures All authors: No reported disclosures.

Background: Smoldering multiple myeloma (SMM) was stratified into risk classes based on several models including Mayo clinic and Spanish myeloma working group models. After the revision of diagnostic criteria for multiple myeloma (MM) in 2014, the ultra-high risk SMM patients (>80% clonal plasma cells at two years) were re-classified as active MM patients. Thus, predictors of progression in patients currently diagnosed as SMM are unknown and reassessment of existing models is required. We aim to identify the risk factors associated with progression in SMM patients classified according to updated guidelines. Methods We performed a literature search following PRISMA guidelines and used following bibliographic databases: MEDLINE (Ovid and PubMed), EMBASE, The Cochrane Library and Cochrane Central Register of Controlled Trials (CENTRAL), as well as annual meetings abstracts from inception till 1st,August 2019. We used MeSH and Emtree terms as well as performed open search for "smoldering multiple myeloma", "smoldering myeloma", and "asymptomatic multiple myeloma". Two independent reviewers screened the literature. We used snowballing technique to screen abstracts and reference within articles to include titles. Cochrane collaboration tool was used to asses risk of bias among included studies Results Our search retrieved 419 titles. After going through the titles and abstracts 38 articles were selected for full text review. Final review led to inclusion of 11 articles. Levels of serum M proteins, percentage of bone marrow plasma cells (BMPCs), serum free light chain ratio (FLCr) and PET/CT scan findings of whole body were most consistently and reliably indicated the progression of SMM to MM (Table 1). New studies are suggesting that B-cell maturation levels (BCMA), evolving M-proteins (eMP) and evolving hemoglobin levels (eHb) are also an accurate measure of SMM progression and should be incorporated in the risk stratification models. A study by Gonsalves WI et al. also suggested that levels of circulating clonal plasma cells with a cutoff of 150 was an important prognostic marker in their study. Immunoparesis status and role of Bence Jones proteins in reliably predicting the progression of SMM was debatable because they were significant in univariate analysis but were not significant in multivariate analysis (Table 1). Conclusion Serum M protein levels (2 g/dL), percentage of BMPCs (20%), serum FLCr (20) and PET/CT scan were reliable in predicting the prognosis of smoldering MM. New techniques like B-cell maturation levels(74.4 ng/mL), evolving M-proteins and evolving hemoglobin levels can play a significant role in proposing future risk predictive models of SMM. Role of immunoparesis and Bence Jones proteins is debatable. Table 1 Disclosures Anwer: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau.

Background Stroke is one of the leading causes of death in the United States and carries a significant risk of morbidity and mortality. P2Y12 inhibitors (Clopidogrel, Ticagrelor etc.) as monotherapy or in combination are used to decrease risk of future ischemic strokes. While standard dosing regimens are currently being used ,the effect of obesity on their efficacy remains unclear. We examined the effect of obesity on the efficacy of P2Y12 inhibitors compared to controls in preventing future incidence of ischemic stroke. Methods We conducted a systematic search on Pubmed, Embase, Cochrane Library, Cochrane Central Register of Controlled Trials and Web of Science to identify relevant randomized clinicals (RCTs) until 31st, July 2019. Our primary outcome of interest was to assess the efficacy of P2Y12 inhibitors (Clopidogrel and Ticagrelor) in preventing recurrent stroke among obese patients with recent stroke or obese individuals at high risk for atherothrombotic events. Obesity was defined as body mass index (BMI) >30kg/m2 and normal BMI was defined as 18 kg/m2 to 25kg/m2. Collected data included dosing regimens, hazard ratio (HR) and confidence interval (CI) for primary outcome in each study arm. We used DerSimonian and Laird random-effects model to estimate pooled HR along with 95% CI using Comprehensive Meta Analysis (CMA) version 3.3. We also performed a sensitivity analysis of the RCTs using Clopidogrel. Heterogeneity was assessed using I2 statistic ( Results Out of 2142 studies initially retrieved, we included three RCTS (n=49134) namely CHARISMA (clopidogrel (Clopi) plus asprin (ASA) vs ASA), PRoFESS (Clopi vs ASA plus dipyridamole (Dipy), and SOCRATES (ticagrelor (Tica) vs ASA). There was no statistical difference in the efficacy of P2Y12 inhibitors in preventing stroke when obese and normal BMI patients were compared (p-value of interaction = 0.80, HR: 0.97 [95% CI: 0.88-1.06]) (figure 1). Sensitivity analysis of patients using Clopi also revealed no statistical difference in preventing future stroke (p-value of interaction = 0.96, HR: 1.03 [95% CI: 0.91-1.16]) (figure 2) in obese vs normal BMI patients. Moreover, there was no difference in the efficacy of P2Y12 inhibitors vs control arm (HR: 0.98 [95% CI: 0.85-1.13], p-value: 0.81, I2=0%) and Clopidogrel only vs Control arm (HR: 1.03 [95% CI: 0.88-1.20], p-value: 0.75, I2=0%) in preventing stroke among obese patients. Conclusion Although Obesity is a known risk factor for cardiovascular events including stroke, and it affects the metabolism of many drugs including anticoagulants among others which was the basis of the idea to look into the published literature on the topic in an attempt to find a correlation between obesity and an increased risk of stroke in patients on P2Y12 inhibitors, there was no difference in the efficacy of standard dose P2Y12 inhibitors in obese patients as compared to normal BMI patients. Sensitivity analysis of trials using standard dose Clopidogrel also revealed no statistical difference, we believe the topic might benefit from further studies . Disclosures Anwer: Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; In-Cyte: Speakers Bureau.

e13096 Background: Several studies have reported the association between atrial fibrillation (AF) and malignant cancer. Recently, results from a large cohort within the Women’s Health Study showed increased incident risk of breast, colon and lung cancer in patients with AF. Therefore, we performed a systematic review to assess the available evidence and a meta-analysis to define the strength of this association. Methods: MEDLINE, Cochrane and Scopus databases were searched for all prospective studies that reported the association between AF and presence of cancer. The HR for incident risk of common cancers was recorded (Breast, Lung, Colorectal) in patients with and without AF. Lung cancer was excluded because the data required for the analysis was not consistently reported. The DerSimonian-Laird random effects meta-analysis was performed to derive pooled Hazard Ratio (HR) estimates for incident risk of colorectal and breast cancer in patients with AF. Q-test was used to assess between-study heterogeneity; I2 statistic was computed to expresses the percentage of the total observed variability due to study heterogeneity. Results: A total of 390,479 participants in 3 prospective studies were included in the analysis. Mean age of participants was 66.3 ± 6.5 with mean follow up for 12.6 years. Patients with atrial fibrillation had 27% more risk of developing colorectal cancer [HR 1.27 (1.07-1.51) p < 0.005, I2= 73%] and 14% more risk of developing breast cancer [HR 1.14 (1.03-1.26) p = 0.01, I2= 37%] as compared to those without atrial fibrillation. Applying these hazard ratios to age adjusted yearly incidence ratios from 2000-2015, one in 5824 new onset AF cases will develop CRC and one in 7474 new onset AF cases will develop breast cancer. Conclusions: There is small but statistically significant increase in risk of subsequent diagnosis of colorectal or breast cancer diagnosis in patients with AF. Shared risk factors such as old age or systemic disease processes may explain this association. While the results of this analysis raise interesting questions for future search, these results should not be used as basis to initiate cancer screening for an occult cancer in a patient with AF.

e12545 Background: Palbociclib(P), Ribociclib(R) and Abemaciclib(A) in combination with Endocrine therapy (ET) have demonstrated progression free survival (PFS) in patients with metastatic hormone receptor positive, HER2-negative breast cancer as compared to ET alone. In the absence of head to head clinical trials and to provide clinical guidance, we performed an indirect comparison for P, R and A using network Meta-Analysis (NMA). Methods: MEDLINE, EMBASE and the Cochrane Library were searched to identify RCTs comparing P+ET, R+ET, A+ ET vs ET alone. NMA for PFS and toxicity endpoints was conducted using a multivariate random-effects meta-regression, using a consistency model, as described by White and colleagues. We used a frequentist approach and provided a point estimate from the network and a 95% CI from the frequency distribution of the estimate. We also estimated the relative ranking of the different treatments for each outcome using the distribution of the ranking probabilities and the surface under the cumulative ranking curves (SUCRA). Risk of bias was assessed using Cochrane Collaboration tool. Results: 8 RCTs were identified including 4580 patients. Risk of bias was low. 5 RCTs tested CDK 4/6 inhibitors in endocrine naive and 2 in the refractory setting, while MONALESSA-3 included patients both with endocrine naive and endocrine resistant disease. In the endocrine naïve patients, PFS for P was similar when compared indirectly with R (HR, 0.95, 95% CI 0.67-1.35) or A (HR, 1.00, 95% CI 0.62-1.61). Similarly, indirect comparison between R vs A did not show any statistical significant (HR, 0.95, 95% CI 0.62-1.45). In endocrine refractory patients, P showed no difference when compared indirectly to A (HR 1.12, 95% CI 0.67-1.87) or R (HR 0.98, 95% CI 0.52-1.86). R vs A did not show any statistically significant PFS either (HR, 1.14, 95% CI 1.61-4.51). P was ranked first in terms of PFS in frontline setting (SUCRA of 70.5) while R ranked first in the refractory setting (SUCRA of 39.5). QT prolongation was reported for R only. P caused more neutropenia while A caused more fatigue, anemia and diarrhea, although the results were not statistically significant. Conclusions: The efficacy of using either palbociclib, ribociclib or abemaciclib in combination with ET was similar in terms of PFS in either endocrine naïve or resistant disease. Palbociclib causes more neutropenia, abemaciclib causes more fatigue, anemia and diarrhea while ribociclib causes QT prolongation.

6596 Background: Several previous systematic reviews and meta-analyses have attempted to summarize toxicity of Immune checkpoint inhibitors (ICIs). However, very soon after each one of these reviews has been published, it became outdated. ICIs are currently used in 14 different cancers and data is rapidly evolving from new clinical trials. A living Systematic review, which is defined as a systematic review that is continually updated to incorporate relevant new evidence as it becomes available, is necessary in this situations. Therefore, we performed an updated systematic review and a meta-analysis which will serve as a foundation of a living Systematic review. Methods: MEDLINE, EMBASE and Cochrane were searched to identify phase 2 and 3 RCTs of PD-1/PD-L1 ICIs. Included studies compared either immunotherapy alone or combination with existing standard of care treatment and reported data for AE’s of interest. DerSimonian-Laird random effects Meta-Analysis was performed to derive pooled odds Ratio (OR) estimates for AE’s of interest. An infrastructure of a living systematic review is being developed and it includes monthly literature searches, cumulative meta-analysis and an online reporting platform. Results: We screened 6746 studies and 31 phase 3 and 2 phase 2 RCTs (n = 21,421) were included in the analysis. 22 RCTs used PD-1/PD-L1 ICIs as a single agent and 11 as a combination therapy. Selected toxicity estimates are summarized in a table. Conclusions: The meta-analysis updates previously published toxicity estimates and provides additional information about the risk of toxicities in single versus combination regimens. We have initiated the first living systematic review in oncology that will be continuously updated, incorporating relevant new evidence as it becomes available, and will provide accurate and up to date toxicity estimates to support clinical decision making. [Table: see text]

e13119 Background: Tyrosine kinase inhibitors (TKIs) are routinely used in the treatment of metastatic RCC and Sunitinib is approved for the use in adjuvant setting. Arterial thromboembolic events (ATEs) have been described with these agents, although the overall risk remains unclear. We did a systematic review and meta-analysis to determine the incidence associated with the use of FDA approved TKIs used in treatment of RCC. Methods: PubMed, EMBASE, Cochrane Central and Scopus databases were searched to identify phase 2 and 3 RCTs of TKI therapy in RCC. Trials were included if they reported ATEs defined as arterial thrombosis, cerebral ischemia or infarction, myocardial ischemia and myocardial infarction. The DerSimonian-Laird random effects meta-analysis was performed using CMAv3 software to derive pooled estimates of incidence rates of ATEs with its 95% confidence interval (CI). I2 statistic was computed to express the percentage of the total observed variability due to study heterogeneity. Risk for bias was assessed using the Cochrane Collaboration’s tool. Results: 1755 studies retrieved in the initial search, and 13 phase 2 and 3 clinical trials (n = 4983) were included in the quantitative analysis. The trials had open label design which can potentially result in bias. Risk of bias was low in all other domains. TKIs used for the treatment of RCC included sunitinib (n = 2632), sorafenib (n = 981), cabozantinib (n = 78), pazopanib (n = 844), axitinib (n = 189) and tivozanib (n = 259). The incidence of ATEs with the use of TKIs was 2.9% (95% CI: 2-3%). Cabozantinib was associated with the highest rate of ATEs (11.5%, 95% CI: 6-21%), followed by sunitinib (2.6%, 95% CI:2-3%) pazopanib (2.6%, 95% CI:2-4%) and axitinib (2.1%, 95% CI: 1-6%). The TKI with lowest event rate of ATE was tivozanib (0.8%, 95% CI:0.2-3%). Conclusions: The use of TKIs is associated with increased risk of developing ATEs. Clinicians should be aware of the possibility of increased ATEs and counsel the patients about this increased risk to enhance the process of informed decision making.

263 Background: In non-metastatic CRPC with short PSA doubling time, APA or ENZA with ADT have shown to slow development of metastasis. We performed an indirect comparison of APA and ENZA clinical effectiveness (efficacy and side effects) using network meta-analysis. Methods: A search of Medline, Embase, Cochrane Library, and Cochrane Central Register of Controlled Trials was performed to identify relevant RCTs. Collected data included hazard ratio (HR) and confidence interval (CI) for primary outcome of median time to metastasis free survival (MFS) and secondary outcomes of median time to overall survival (OS), PSA progression, initiation of cytotoxic therapy and number of adverse events (AE) in each study arm. Risk for bias was assessed using the Cochrane Collaboration’s tool. We used a fixed effects model using Bayesian approach to generate pooled estimates. Results: Two randomized trials (n=2608) were analyzed. SPARTAN trial compared APA plus ADT to ADT alone and PROSPER compared ENZA plus ADT to ADT alone. Risk of bias was low. There were no statistically significant differences between APA and ENZA in MFS, OS, median time to PSA progression and initiation of cytotoxic therapy. The MFS endpoint hazard ratio (HR) was 0.97 (95% CI 0.73-1.28) for comparing the two drugs. APA had fewer reports of hypertension (HR 0.54, 95% CI 0.31–0.91) compared to enzalutamide. However, no significant differences were observed in other AEs including grade 3 or higher AE, serious AE, AE leading to death or trial discontinuation. Common AEs (nausea, diarrhea, fall, dizziness, arthralgia, weight loss) and AEs of special interests (mental impairment disorders, seizures) were also comparable between APA and ENZA. Conclusions: In non-metastatic CRPC with short PSA doubling time, APA and ENZA showed similar time to metastasis free survival. APA was associated with lower incidence of hypertension than ENZA; otherwise, side effect profile was similar. Given similar efficacy and risk profile demonstrated in this study, clinical decision making should depend on other factors such as cost and availability.

Introduction: Targeted immunotherapy includes monoclonal antibodies, antibody-drug conjugates and chimeric antigen receptor T-cells (CAR-T cells). With recent advancements, the study of novel agents that target various cellular receptors involved on myeloma cells, have been actively pursued. The main aim of our study is to review and summarize published literature on the efficacy and safety of these targeted immunotherapies in patients (pts) with multiple myeloma (MM). Methods: We performed a comprehensive literature search on articles published after 2012 using the following databases (Pubmed, Embase, Cochrane, Web of Science and Clinicaltrials.gov). We included 6 completed and 16 ongoing phase II, III trials involving both newly diagnosed MM (NDMM) as well as relapsed/refractory MM (RRMM) pts. Results: Siltuximab: We included 3 phase II trials of Siltuximab (S) involving 243 pts. One hundred ninety-one pts had RRMM while 52 pts had NDMM. The overall response rate (ORR) was 45.50 % and 88% in RRMM and NDMM pts respectively. In a phase II trial involving 52 transplant ineligible NDMM pts, S (11mg/kg) in combination with bortezomib (V), melphalan (M) and prednisolone was given. In 49 evaluable pts, the ORR was 88% with complete response (CR) in 27% pts, very good partial response (VGPR) in 71% pts, and partial response (PR) in 61% pts. The median progression-free survival (mPFS) was 17 months (mo) while the overall survival (OS) at 1 year (y) was 88%. The most common grade 3 and 4 adverse effects (AEs) were neutropenia (62%), thrombocytopenia (44%), pneumonia (17%), and anemia (13%). In a phase II trial involving 142 pts with RRMM, S (6mg/kg) in combination with V was given. The number (no.) of prior therapies were 1-3. In 131 evaluable pts, ORR was 55% with CR in 11% pts and PR in 44% pts. The mPFS was 8 mo (p=0.345) while the OS at 1 y was 81%. The most common grade 3 and 4 AEs were neutropenia (49%), and thrombocytopenia (48%). In another phase II trial involving 49 pts with RRMM, S (6mg/kg) in combination with dexamethasone (D) was given. The median no. of prior therapies was 4. In 47 evaluable pts, the ORR was 19% while the mPFS and OS were 3.7 mo (95% CI= 2.8-4.9) and 20.4 mo (95% CI= 11.4-32.3) respectively. The most common grade 3 and 4 AEs were neutropenia (36.7%), thrombocytopenia (53%), anemia (32.6%), leukopenia (8%), and fatigue (16.3%). Only one ongoing phase II study was found (Table 2). No phase III studies were found. Isatuximab (SAR650984): In a phase II trial involving 97 pts with RRMM, escalating doses of isatuximab (3-20 mg/kg) were given. The median age of pts was 62.5 y. The median no. of prior therapies was 5. At dose ≥10 mg/kg, maximum ORR of 24% was observed. The most common AEs were nausea (33%), fatigue (30%), dyspnea (26%), and cough (24%). Two ongoing phase II studies and 3 ongoing phase III studies were found (Table 2). Pembrolizumab and nivolumab: In a phase II study involving 48 pts with RRMM, pembrolizumab (200mg) in combination with pomalidomide and D was given. The median no. of prior therapies was 3. The ORR was 60% with CR in 8.33% pts, VGPR in 19% pts, and PR in 33% pts. The mPFS was 17.4 mo. The most common grade 3 and 4 AEs were neutropenia (42%), thrombocytopenia (13%), anemia (21%), and lymphopenia (15%). Two ongoing phase II/III studies each was found for Pembrolizumab. One ongoing phase II and III study each was found for nivolumab (Table 2). Tabalumab: In a phase II trial involving 148 pts with RRMM, tabalumab (100-300mg) in combination with D and V was given. The ORR was 58.1-59.5%. The mPFS was 6.6-7.5 mo. The most common grade 3 and 4 AEs were thrombocytopenia (15.6%), anemia (10.9%), and fatigue (7.5%). No phase III studies were found. Conclusion: Our study demonstrated that siltuximab combination regimens have shown excellent efficacy in NDMM pts compared to RRMM pts with an ORR of 88% vs. 46%. Similarly, better OS (88% vs. 81%) and mPFS (17 months vs. 8 months) were found in NDMM pts compared to RRMM pts. Neutropenia and thrombocytopenia were the major side effects reported with siltuximab. Pembrolizumab and tabalumab have shown moderate efficacy in RRMM pts with an ORR of 60%. However, isatuximab has shown mild efficacy in RRMM pts with an ORR of 24%. These drugs are well tolerated compared to siltuximab. Significant data in the literature are lacking and data from larger study population are needed. Disclosures No relevant conflicts of interest to declare.

Introduction: After establishing the diagnosis of acute myeloid leukemia (AML), remission induction chemotherapy is started with curative intent. Due to paucity of direct therapeutic comparison of induction regimens, relative efficacy of two drug standard regimens and three drug induction regimens among newly diagnosed young ( Methods: The literature search was performed on PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science and Clinicaltrials.gov from each database's earliest inception through July 28th, 2018 without language restrictions. Included trials assessed CR after one cycle of induction chemotherapy in adults (17-60 years) diagnosed with AML. We excluded studies with patients ≥60 years, who received double induction chemotherapy or two drug regimens other than standard chemotherapy. Data extraction and quality assessment of trials using GRADE approach was done by two independent reviewers. Any discrepancy was resolved by consensus or consulting the primary investigators. A conventional NMA assuming random effects was fitted to evaluate the pooled effect of induction therapy on CR with standard chemotherapy as reference treatment. The model estimated relative efficacy for each direct and indirect comparison, measured as odds ratio (OR), with uncertainty captured as 95% confidence interval (CI). Chemotherapy regimens were ranked based on the surface under the cumulative ranking curve analysis (SUCRA) with higher values reflecting greater CR. All statistical analyses were conducted using STATA, version 15 (Stata Corp LP, College Station, TX). Results: Our analysis included 8 RCTs (n= 6830) including nine treatment regimens (7+3 or 7+3+X): cytarabine + daunorubicin (DA), cytarabine + idarubicin (IA), DA+ gemtuzumab ozogamicin (DAGo), DA+ 6-thioguanine (DAT), IA+ granulocyte colony stimulating factor (IAG), DA + midostaurin (DAM), DA + cladribine (DAC), DA + fludarabine (DAF), IA + cladribine (IAC). Average median age of included patients was 38.1 years (range = 45-60) and all patients had newly diagnosed primary AML. 10% had favorable cytogenetics, 62% intermediate and 27% had high risk cytogenetics. Through the network meta-analysis IA achieved highest CR rates [OR of 1.85 (95% C.I: 1.02-3.35)] compared to other included regimens (Figure 1). There was no statistically significant difference in achieving CR between anthracycline based standard chemotherapy versus three drug regimens [IAC = 0.85 (0.25-2.87), DAGo = 1.09 (0.75-1.59), DAF = 1.10 (0.73-1.63), DAT = 1.19 (0.78-1.82), DAM = 1.24 (0.88-1.77), DAC = 1.38 (1.00-1.90), AIG = 1.83 (0.90-3.75)] (Figure 2). A dose specific subgroup analysis of daunorubicin (60 mg/m2) containing regimens showed no statistical difference between different therapies [DAG = 1.09 (95% CI: 0.75-1.59), DAF = 1.10 (95% CI:0.73-1.63), DAM = 1.24 (0.88-1.77), DAC =1.38 (1.00-1.90)] (Figure 1). Conclusion: Our results demonstrate that combination of cytarabine with idarubicin achieved highest rates of CR after one cycle of induction therapy in newly diagnosed young AML patients. There was no statistical difference between the efficacy of other standard regimens and three drug regimens. Head-to-head trials are required to reliably demonstrate the relative efficacy of these regimens. Disclosures No relevant conflicts of interest to declare.

Background: Lenalidomide (Len) and low-dose dexamethasone (dex) in combination with proteasome inhibitor (PI) or cytotoxic agent is an integral part of front-line therapy in multiple myeloma (MM). Use of Lenalidomide (Len) in MM had demonstrated an increased risk of venous thromboembolism (VTE) in initial studies which led to the incorporation of routine thromboprophylaxis with Len-based regimens. Existing estimate of VTE incidence from a prior analysis on Len-based regimens in newly diagnosed MM is 0.8 per 100 patient-cycles [Carrier et al. 2011]. However, there is a gap in literature on the incidence of VTE in patients receiving contemporary Len-based combination regimens along with adequate thromboprophylaxis. Hence, we conducted a systematic review and meta-analysis of clinical trials to assess the incidence of VTE with Len-based regimens in newly diagnosed MM patients. Method: We queried Ovid Medline, Ovid Embase and Cochrane Library databases to obtain relevant studies until March 2018. We included all phase I-III clinical trials testing a Len-based combination regimen for induction +/- consolidation therapy along with protocol-mandated thromboprophylaxis. VTE was defined as deep vein thrombosis or pulmonary embolism (CTCAE Grade 2 or above). Our primary outcome was pooled incidence of VTE events per patient-cycle, which was subsequently converted to VTE events per 100 patient-cycle for ease of comparison with existing literature in MM. We performed meta-analyses with random-effects model using a comprehensive meta-analysis software. Heterogeneity was calculated using I2 statistic and a value Results: Initial search generated 1069 citations. After screening, 15 clinical trials with 3381 patients were included. Among 15 trials, 4 were phase I/II, 6 were phase II and 5 were phase III. All but one trial used low-dose dex. The pooled incidence of VTE events was 0.4 per 100 patient-cycles [95% CI. 0.3-0.5; I2: 70%]. Incidence rate of VTE in individual studies are summarized in Table I. The Forest Plot is shown in Figure I. Subsequently, we performed pre-specified subgroup analyses on trials with Len-dex, Len-dex + PI, Len-dex + doxorubicin and Len with Melphalan-Prednisone (MPR). The pooled incidence of VTE per 100-patient cycle with Len-dex was 0.3 [95% CI. 0.1-0.4; I2:92%], Len-dex with PI was 0.9 [95% CI. 0.3-1.6; I2: 69%], Len-dex with doxorubicin was1.5 [95% CI. 0.7-2.2; I2: 0%] and MPR was 0.3 [95% CI. 0.2-0.4; I2: 0%]. Notably, the incidence of VTE was higher with Carfilzomib-Len-dex when compared to Bortezomib-Len-dex regimens. Two trials with Len-dex + Doxorubicin had a higher rate of VTE irrespective of the dex dose. The most common modes of thromboprophylaxis used were ASA (range, 70-325 mg) and low molecular weight heparin. Conclusion: Patients with newly diagnosed MM receiving contemporary Len-based regimens have a significant incidence of VTE despite adequate thromboprophylaxis. However, the incidence rate compares favorably with prior estimate. The rate of VTE was highest with the use of Len-dex + Doxorubicin triplet regimen. In the Len-dex+PI subgroup, the incidence of VTE was higher in trials using Carfilzomib-Len-dex compared to Bortezomib-Len-dex regimen. These findings can be clinically applied at an individual level to choose a Len-based combination regimen based on the risk of thrombosis. New prophylactic agents like direct oral anticoagulants should be tested to further decrease the rate of VTE with Len-based combination regimens. Disclosures Khorana: Janssen: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; Bayer: Consultancy. Majhail:Anthem, Inc.: Consultancy; Incyte: Honoraria; Atara: Honoraria.