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Treatment options for multicentric Castleman disease (MCD) remain limited. The only FDA-approved drug is siltuximab for idiopathic MCD (iMCD), but the response rate with siltuximab is less than 50%. We performed a systematic review to examine the efficacy and safety of various regimens used for the treatment of MCD.A database search on PubMed, Embase, Cochrane, Web of Science, and Clinicaltrials.gov using the terms "Castleman disease," "treatment outcome," and "patient safety" was done.Results from a randomized controlled trial and an extension study highlighted the efficacy and long-term safety of siltuximab for iMCD; other trials showed tocilizumab to be a suitable alternative. A recent trial reported high response rates with thalidomide in iMCD patients. Promising results were reported for bortezomib in relapsed/ refractory MCD. For human herpesvirus-8 (HHV8)-associated MCD, rituximab along with doxorubicin therapy followed by maintenance with zidovudine and valganciclovir is the most effective therapy. A single-arm trial has highlighted the potential role of tocilizumab in HHV8-MCD. Data for these regimens are limited and mostly comprise nonrandomized trials. Further research on emerging agents could have a major impact on the treatment of this rare disease.

Adult T-cell leukemia/lymphoma (ATLL) remains challenging to treat and has dismal outcome. Allogeneic stem-cell transplantation (allo-SCT) has promising results, but data remain scarce. In this single-center retrospective analysis of 100 patients with ATLL from north America (67 acute, 22 lymphomatous), 17 underwent allo-SCT and 5 autologous SCT (ASCT), with a median follow-up of 65 months. Post-transplant 3-years relapse incidence (RI) and non-relapse mortality (NRM) were 51% and 37%, respectively, and 3-year progression-free survival (PFS) and overall survival (OS) were 31% and 35%, respectively. ASCT 1-year RI was 80% compared to 30% in allo-SCT (p = 0.03). After adjusting for immortal-time bias, allo-SCT had significantly improved OS (HR = 0.4, p = 0.01). In exploratory multivariate analysis, patients achieving first complete response and Karnofsky score ≥ 90 had significantly better outcomes, as did Black patients, compared to Hispanics, who had worse outcome. In transplanted patients, 14 died within 2 years, 4 of which ASCT recipients. Our data are the largest ATLL transplant cohort presented to date outside of Japan and Europe. We show that allo-SCT, but not ASCT, is a valid option in select ATLL patients, and can induce long term survival, with 40% of patients alive after more than 5 years.

VEXAS (vacuoles, E1 enzyme, X linked, autoinflammatory, somatic) syndrome is a novel inflammatory syndrome that was first described in December 2020. Patients with VEXAS syndrome have a somatic mutation in the UBA1 gene, inflammatory conditions and usually haematological conditions. Haematological conditions reported in patients with VEXAS syndrome include myelodysplastic syndrome (MDS), clonal cytopenia of undetermined significance, plasma cell neoplasm including multiple myeloma/monoclonal gammopathy of undetermined significance, haemophagocytic lymphohistiocytosis and monoclonal B-cell lymphocytosis. Here we describe a patient with VEXAS syndrome who had a progression of MDS to MDS/myeloproliferative neoplasm overlap syndrome. The ocular findings so far reported in these patients include episcleritis, uveitis, blepharitis and orbital cellulitis. Here we report retinal detachment as a clinical feature of VEXAS syndrome. This finding has a significant implication in patient management as it warrants higher vigilance for this sight-threatening complication.

Treatment options are limited for multiple myeloma patients who have developed four/five drug-refractory disease. Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of RRMM. The toxicity profile of these drugs is a concern since these agents are used in patients who have already undergone multiple lines of treatment. In this review, we discuss the toxicity profile and strategies for the management of toxicities of Sel and belamaf for the treatment of RRMM. We conducted a comprehensive literature search on PubMed, Embase, Cochrane, and Clinicaltrials.gov using the terms “selinexor”, “belantamab”, “belamaf”, and “multiple myeloma” without applying any limitations based on the date of the study, language, or country of origin. The most common hematological toxicity associated with these two drugs is thrombocytopenia. Cytopenias, constitutional symptoms, gastrointestinal effects, and hyponatremia are the major toxicities of Sel. Keratopathy and anemia are the major toxicities of belamaf. Treatment modifications and dose interruption are usually needed when side effects are more than grade II. As these are newer drugs with limited data, continuous surveillance and monitoring are warranted during the treatment course with early mitigation strategies.

Seasonal flu or influenza is an acute respiratory illness caused by Influenza virus A and B. The disease is usually self-limiting, but can occasionally lead to dire complications. To prevent the occurrence of these complications, many preventive, as well as therapeutic remedies, have been implicated. Vaccines have shown to reduce morbidity associated with influenza viral infection. In addition to this, if an infection does occur, it may lead to adversities, especially in patients with extremes of ages, i.e., less than 12 and more than 65. The advent of anti-viral medications has helped in a significant reduction in the symptoms associated with this disease. But, as resistance to these chemicals has emerged, this is now contributing to the widespread endemics and pandemics. With this understanding, newer and better drugs are being introduced in the market. One such medication is Baloxavir, a modified version of the novel anti-viral drugs. We conducted a thorough electronic data search on PubMed and Google Scholar. Articles were filtered using the exclusion criteria of, “co-morbid conditions,” immunodeficiency state,” “Chronic Obstructive Pulmonary Disease,” etc. The extracted articles were within a five-year time frame and were free full text. Further information was extracted using cross-references. Articles were screened for duplication. In this literature review, we describe in detail the advantages of Baloxavir to reduce the morbidity associated with Influenza infection.

Renal cell carcinoma can have lung metastasis even after a long interval of radical nephrectomy (16 years after nephrectomy in our case). If any pulmonary nodule is diagnosed with a history of RCC, pulmonary metastasis of RCC should be suspected and should be appropriately treated.

With recent advances in novel chemotherapeutic agents and increasing use of autologous hematopoietic stem cell transplant, there has been a significant improvement in outcomes for patients with AL Amyloidosis. Daratumumab, with its excellent safety and efficacy profile, appears to be an ideal treatment option for patients with newly diagnosed as well as relapsed refractory AL amyloidosis. In this systematic review, we analyzed the published literature on the role of Daratumumab in pretreated relapsed and refractory AL-amyloidosis patients using PubMed, Embase, Cochrane, and clinicaltrials.gov databases. A total of 16 studies evaluated the role of Daratumumab as monotherapy (DMT) or in combination with other chemotherapeutic agents (DCT). DMT and DCT were associated with promising efficacy with hematologic and organ responses (cardiac/renal) seen in 50-90% and 50-80% of the patients, respectively. Daratumumab appeared to be well tolerated with no significant treatment-related adverse events as DMT or DCT.

There is increasing evidence regarding the role of various maintenance therapy (MT) strategies after initial induction to treat newly diagnosed transplant-ineligible patients with MM. We reviewed the literature on available regimens for patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM). Lenalidomide (R)-based regimens are still the front-line therapy, but there is an increasing use of bortezomib-based regimens. The MT regimen is mainly based on the initial induction regimen. MT has shown survival benefits compared with patients without maintenance therapy. The most common adverse effects of MT include anemia, neutropenia, thrombocytopenia, infections, and peripheral neuropathy. In conclusion, induction followed by maintenance based on lenalidomide, bortezomib, ixazomib, or daratumumab-based regimens has shown promising results. Therefore, it is essential to conduct more clinical trials to better understand the role of MT in the treatment of NDMM patients who are not candidates for autologous stem cell transplantation.

Pneumocystis pneumonia (PCP) is an opportunistic infection caused by Pneumocystis jirovecii. PCP due to immunosuppressive drugs is rarely reported in the literature. Herein we present a case of PCP in a 49-year-old patient who presented with progressive shortness of breath, dry cough, and low-grade fever. History revealed that he was taking prednisolone daily for his hyperactive airway disease. His temperature was 99oF, and he had bilateral crackles in the lungs with resonant wheezing. High-resolution computed tomography showed diffuse ground-glass haze and cystic lesions in the middle and upper zones of both lungs. He was commenced on intravenous ceftriaxone and methylprednisolone based on provisional diagnosis of interstitial pneumonia. However, his condition worsened. His human immunodeficiency virus (HIV) test was reactive, and his CD4+ count was 275 cells/mm3. Bronchoalveolar lavage revealed PCP by direct immunofluorescent assay. Additional serum testing revealed marked elevation of beta-D-glucan, consistent with PCP diagnosis due to glucocorticoid use. Trimethoprim-sulfamethoxazole and voriconazole were initiated, and his respiratory symptoms started improving. His respiratory condition improved on day 9, and he was discharged with follow-up.

A 47-year-old female with a past medical history of morbid obesity and hypertension presented with acute onset dizziness that started while she was at work one evening. She did not have chest pain or dyspnea. She had vital signs within an acceptable range, oxygen saturation of 98%-99%, and was not in acute distress. Examination including the Dix-Hallpike maneuver was unremarkable. Computed tomography angiography (CTA) of the head and neck disclosed bilateral pulmonary embolism without any evidence of cerebral ischemia. CTA chest confirmed the diagnosis of bilateral pulmonary emboli. Importantly, besides the obesity, the patient did not have any other risk factors of pulmonary embolism including recent immobilization, surgery, hormonal therapy or contraceptive use, and personal or family history of thromboembolic disorders. However, she was diagnosed with COVID-19 infection six months back with symptoms not requiring hospitalization. Following further workup for her dizziness and neurology evaluation, in the absence of any other plausible etiology, her presenting symptom was attributed to the atypical presentation of pulmonary embolism. She was treated with heparin in the hospital and discharged on apixaban. Her symptoms had resolved at the time of discharge.

An intense itching localized to dermatomes is a rare symptom of multiple sclerosis (MS). Herein, we report a case of a 45-year-old female who presented with severe itching and tingling sensation, gait disturbance, and bilateral paresthesia for one week. She also had a history of multiple admission in the hospital due to recurrent walking abnormalities and numbness and tingling of both hands associated with intermittent psychiatric symptoms. The neurological examination revealed spastic quadriparesis with lower limb muscles affected more than the upper limbs, numbness, and sensory loss in the upper extremities in the glove and stocking pattern. Magnetic resonance imaging (MRI) revealed multiple small rounded periventricular plaques in both hemispheres and along the long axis of the corpus callosum (fluid-attenuated inversion recovery/FLAIR sequence), and cerebrospinal fluid analysis revealed the presence of oligoclonal bands, suggestive of MS. She was commenced on methylprednisolone and carbamazepine, leading to progressive resolution of her signs and symptoms. She was discharged with monthly natalizumab, and she was doing well on her follow-up.

A 10-year-old boy with no past medical history presented with complaints of nausea and vomiting associated with morning headache for the last month. Ophthalmic nerve and eye exam showed diplopia and strabismus with no other significant findings on physical and neurological examination. Magnetic resonance imaging (MRI) of the brain revealed a homogenous hyperdense and enhancing mass in the pineal region. The endoscopic biopsy of the pineal region demonstrated the cells with highly pleomorphic and hyperchromatic nuclei with an increase in mitotic activity. There were many vessels but no area of vascular proliferation and necrosis. Granular bodies with eosinophilia were identified. Immunohistochemistry was positive for class III b-tubulin with epidermal growth factor receptor (EGFR) staining and glial fibrillary acidic protein (GFAP). Immunostaining was positive for p53, Phosphatase and Tensin homolog (PTEN), and oligodendrocyte transcription factor (OLIG2), while staining for cluster of differentiation (CD)34, cytokeratin (CK), human melanoma black (HMB)45, and isocitrate dehydrogenase (IDH)-R132H mutation was negative, consistent with atypical pleomorphic neoplasm of the pineal region. The patient underwent tumor resection via a sub-occipital trans-tentorial approach, followed by one dose of chemotherapy. The patient experienced a resolution of the symptom and was doing well on his bi-monthly follow up.

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.

Introduction: Multicentric Castleman disease (MCD) is a rare lymphoproliferative disorder characterized by lymph node enlargement in multiple regions of the body. It includes two heterogeneous subtypes: human herpesvirus 8 (HHV-8) associated MCD and idiopathic MCD (iMCD). This study is focused on the efficacy and safety of treatment regimens for MCD in clinical trials. Methods: A systematic literature search was conducted using PubMed, Embase, Cochrane, Web of Science, Clinicaltrials.gov, ASH, and ASCO meeting websites from inception to May 9, 2021. The initial search revealed 1323 articles. After excluding reviews, duplicates, and non-relevant articles, we included data from 13 articles. Results: Data on 311 patients was included. Siltuximab based regimens: In the two clinical trials where siltuximab was used for iMCD, Cheson criteria (modified to include cutaneous lesions) was used to assess response. In a phase 2 trial by Van Rhee et al. (2014, n=79), the overall response rate (ORR) was 34% vs 0% and grade≥3 adverse events (AEs) were seen in 47% vs 54% of the siltuximab (n=53) and placebo (n=26) groups respectively. In a phase 1 trial by Kurzrock et al. (2013, n=37), 86% of patients improved in at least one clinical benefit response (CBR) component, 33% had confirmed radiological ORR, and 11% had grade≥3 AEs. Van Rhee et al. (2020, n=60) conducted an extension analysis of patients from these two trials. After a median follow-up of 6 years (IQR 5∙11-7∙76), serious AEs were reported in 42% of patients and stable disease (SD) or better of up to 6 years was recorded in 70% of patients. Tocilizumab based regimens: In a phase 2 trial by Ramaswami et al. (2020, n=8), ORR was 63% vs 100%, progression-free survival (PFS) at 4 months was 25% vs 33%, and grade≥3 AEs were reported in 25% vs 67% of HHV-8 associated MCD patients receiving tocilizumab alone vs tocilizumab alongside zidovudine (AZT) and valganciclovir (VGC), respectively. Nishimoto et al. (2005, n=28) reported a 30% reduction (p Rituximab based regimens: In a phase 2 trial by Bower et al. (2007, n=21), 67% of HIV-associated MCD patients had a partial response (PR) and 29% had SD on rituximab. The 2-year overall survival (OS) and relapse-free survival were 95% (95% CI, 86% to 100%) and 79% (95% CI, 52% to 100%) respectively. No grade≥3 toxicity was observed. In a phase 2 trial by Gerard et al. (2007, n=24) on rituximab in HIV-associated MCD, the sustained remission rate was 92% (95% CI, 80% to 103%) at day 60. Estimated 1-year OS was 92% (95%CI, 71% to 98%). In a phase 2 trial by Uldrick et al. (2014, n=17), rituximab and doxorubicin (R-dox) were administered to HHV-8 MCD patients. ORR was 82% and OS was 81% (95%CI, 57% to 93%) at 3 years. Ramaswami et al. (2021) reported survival outcomes from the same trial. The 5-year PFS with rituximab (n=8), R-dox followed by no maintenance (n=16), R-dox followed by AZT+VGC (n=10) and R-dox followed by interferon-alpha (n=10) were 71% (95%CI, 26% to 92%), 62% (95%CI, 23% to 85%), 87% (95%CI, 39% to 98%) and 70% (95%CI, 33% to 89%) respectively. Immunomodulatory drug-based regimens: In a phase 2 study by Zhang et al. (2019, n=25), ORR was 48% in iMCD patients on thalidomide, cyclophosphamide, and prednisone. Estimated 1-year OS and PFS were 88% and 60% respectively. Grade≥3 AEs were rash and pneumonitis in 1 (4%) patient each. Proteasome Inhibitor based regimens: Zhang et al. (2020, n=20) reported the efficacy of bortezomib, cyclophosphamide, and dexamethasone in relapsed and refractory (R/R) iMCD patients. Seventy-five percent had PR and 10% had SD. Estimated 1-year PFS and OS were 85% and 90% respectively. No grade≥3 AEs occurred. Antiviral Regimens: In a phase 2 trial by Uldrick et al. (2011, n=14), ORR was 28% in HHV-8 MCD patients on AZT and VGC. Clinical complete response (CR) occurred in 50% of patients. Ramaswami et al. (2021) reported the efficacy of AZT+VGC in 17 patients from the same trial. The 5-year PFS was 26% (95%CI, 8% to 49%). Conclusion: Siltuximab- and thalidomide-based regimens have acceptable efficacy and safety profiles for the treatment of iMCD. Bortezomib appears to be effective for R/R iMCD. Tocilizumab and rituximab showed promising outcomes for the treatment of HHV-8 associated MCD. However, more prospective clinical trials need to be conducted. Figure 1 Figure 1. Disclosures Anwer: Allogene Therapeutics: Research Funding; BMS / Celgene: Honoraria, Research Funding; GlaxoSmithKline: Research Funding; Janssen pharmaceutical: Honoraria, Research Funding.

Introduction: Myeloproliferative neoplasms (MPN) include essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). Pregnancy in the presence of MPN increases the risk of thrombosis, hemorrhagic events, pre-eclampsia, progression to myelofibrosis (MF) or acute myeloid leukemia (AML) leading to poor fetal outcome. Methods: We conducted a literature search on PubMed, Embase, Web of Science, and Clinicaltrials.gov using MeSH terms and key words for MPN, PV, and ET from date of inception to January 2021. We excluded studies reporting less than 10 patients and those not in English language. Results: ET studies: How et al. (121 pregnancy (P)/52 women (W)) reported Aspirin (ASA) was protective and was used in 51.2% P (n=62/107) with OR (odd's ratio) of 0.304 (p=0.048; 90% CI 0.102-0.795). Similar benefit of ASA was also reported by Gangat e t al.(2009) (63P/36W ; P loss 21% in 24 patients receiving ASA vs 75% in 12 patients not receiving ASA), Niittyvuopio et al. (40P/16W; live births (LB) in all 13 P treated with ASA or ASA with prior cytoreduction therapy vs 67% complications and 56% loss of P in patients not treated with ASA), Randi et al. (1999) (16P/13W; 7/13 LB occurred on ASA, and only one P was lost on ASA), Bangerter et al.( 17P/9W; 100% P treated with ASA resulted in LB vs 45% LB in P without any treatment, p=0.04), and Pagliaro et al. (15P/9W; ASA monotherapy (n=3/15P) or ASA+ subcutaneous heparin (n=7/15P) resulted in nine LB). Cincotta e t al. (30P/12W) reported 79% LB with ASA or IFN-α vs 38% LB without any treatment (p=0.06). Among the treatment cohort, 5/7 patients on ASA had a LB, and all 4/4 patients on IFN-α had a LB. However, Beressi et al. (31P/18W) reported 4/8 untreated and 10/19 ASA treated P were lost with no statistically significant benefit. Palandri et al. reported 24P/13W treated with IFN-α (n=1), IFN-α + ASA (n=2) and ASA alone (n=9). The LB rate was not influenced significantly with treatment at conception (treated vs. untreated: 8/12 vs. 7/12, P=0.99). Melillo e t al. (122P/92W) reported no benefit with ASA. IFN-α had positive outcomes with 95% LB than patients not receiving IFN-α with 71.6% LB (OR 0.10 (95%CI: 0.013-0.846, p=0.034)). JAK2 mutation was associated with poorer outcomes (OR 6.19; 95%CI: 1.17-32.61; p=0.038). Wright et al. (43P/20W) reported no statistically significant difference between no treatment (n=16/43), ASA alone (n=24/43), ASA+cytoreduction (n=2/43), and low molecular weight heparin (LMWH) (n=1/43) groups. Passamonti et al.( 96P/58W ) reported statistically significant worse outcomes in JAK2 negative patients, no statistically significant benefit in JAK2 positive patients (p=0.05) with ASA and higher complications with conception while on cytoreduction therapy (n=6/13 abortion, n=3/13 pre-eclampsia). ET + Other MPN studies: Gangat et al. (2020) reported (152W ET and 36W PV) that in 95P/55W with ET, 60% pregnancy loss occurred without ASA vs 27% with ASA (p=0.02). All 4/36W with PV who were treated with one or more of ASA, enoxaparin, and hydroxyurea delivered LB, and 50% developed venous thromboembolism. Sokolowska et al. reported 104P/60W with MPN (47 ET, 3 PV, and 10 PMF) treated with various combinations of cytoreduction therapy (IFN-α in 48P, apheresis in 1P and anticoagulation (LMWH+ASA in 10, LMWH alone in 19 and ASA alone in 24P) during the pregnancy with 72.1% LB. Lapoirie et al. stratified 27P/14W (ET 19P/9W, PV 8P/5W) with MPN into high risk (67%) and standard risk and found significant P loss in all high-risk P that did not receive ASA (n=2). Maternal complications occurred in 3 high-risk P that received ASA. 77% of P treated with ASA, LMWH, or both resulted in a LB. Alimam et al. (58W; ET 47, PV 5, PMF 5, MPN-unclassified 1) reported better than predicted outcomes in 88% of women receiving ASA during P, 38% receiving ASA + prophylactic LMWH and 3% receiving ASA + therapeutic LMWH resulting in 58 LB with a P loss rate of 1.7/100 (95% CI; 0.04-9.24). PV studies: Irene et al. (24P/15W) reported a 40% incidence of P loss without antithrombotic therapy vs 10.5 % P loss receiving ASA, LMWH, or both. Willie e t al. divided 32P/14W with PV into two groups (treatment group: 18 P, treated with ASA during P and LMWH for six weeks postpartum; non-treatment group: 14 P) with 72% vs 14% LB respectively. Conclusion: Use of ASA, LMWH and cytoreductive therapy is the existing practice for pregnancies with MPN. However, proper evidence via a RCT is an unmet need. Figure 1 Figure 1. Disclosures Anwer: Janssen pharmaceutical: Honoraria, Research Funding; BMS / Celgene: Honoraria, Research Funding; Allogene Therapeutics: 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: Daratumumab (Dara) is a human an IgG1k monoclonal antibody that targets the CD38 which is overexpressed in the malignant cells of multiple myeloma (MM). Its use has been approved for use as a single agent as well as in combination therapy for the treatment of both newly diagnosed MM (NDMM) and relapsed/refractory MM (RRMM). This review highlights the efficacy and safety of Dara in the four-drug regimen in NDMM patients (pts). Methods: We conducted a literature search using four databases (PubMed, Embase, Cochrane, and Clinicaltrials.gov). Our search strategy included Medical Subject Headings (MeSH terms) and keywords for multiple myeloma and daratumumab including trade names and generic names from the date of inception to June 2020. After excluding review articles, duplicates, and non-relevant articles, we included three phase III trials out of 588 articles reporting Dara addition to the standard of care four drug regimens for NDMM pts. Results: A total of 1998 patients were enrolled and evaluated in three-phase III randomized controlled trials. A total of 997 patients were evaluated in the Dara group and 1001 patients were evaluated in the control group. Total 1292 were transplant eligible and 706 patients were transplant ineligible. Transplant eligible Moreau et al. (2019) studied the efficacy of Dara + bortezomib (V) + thalidomide (T) + dexamethasone (d) vs VTd in newly diagnosed MM (NDMM) pts (n=1085) in CASSIOPEIA phase III trial. Addition of Dara to VTd group showed marked improvement in progression-free survival (PFS): 93% vs 85% at 18 months (hazard ratio (HR) 0.42 [0.34-0.51]; p Vorhees et al. (2020) reported addition of Dara to lenolidamide (R), and Vd in GRIFFIN study in NDMM patients (n= 207). Addition of Dara to VRd resulted in improved PFS: 95.8% ((95% CI, 89.2- 98.4) vs 89.8% ((95% CI, 77.1-95.7) at 24 months), and ORR of 99% (Odd's ratio (OR) 8.75 with 95% CI: 1.08-71.01; p=0.0160) in Dara + VRd group vs VRd group (91.8%). MRD status in bone marrow was also higher in Dara group as compared to control group (51% vs 20.4%) (p Mateos et al. (2018) reported the role of Dara + V + melphalan (M) + prednisone (P) vs VMP in NDMM pts (n=706) in a phase III trial (Alcyone). Addition of Dara to VMP group showed marked improvement in PFS: 63% vs 36 at 24 months (HR: 0.47, 95% CI 0.33-0.67, p Significant toxicities in phase III trials mainly included pancytopenias and opportunistic infections (Table 2). Conclusion: NDMM treatment with Dara in four-drug regimens (VTd, VMP, VRd) has shown promising outcomes with improved efficacy and higher negative MRD status, providing a benchmark for future studies. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Background: Hepatic veno-occlusive disease (VOD) also termed as sinusoidal obstruction syndrome (SOS) is a lethal complication seen after haematopoietic stem cell transplantation (HSCT). There are a limited number of options for prevention of this fatal complication. Recombinant thrombomodulin (rTM), an endothelial anticoagulant co-factor, has been shown to help prevent veno-occlusive complications after stem cell transplantation. Various trials have shown safety and efficacy of recombinant thrombomodulin in preventing SOS. Methods: A search was performed on PubMed, Cochrane, Embase, and Web of Science. We used the following keywords, "thrombomodulin" AND "stem cell transplantation" from the inception of literature till June 2020. Out of 239 articles, we screened and included nine trials (N=850) in the systematic review and meta-analysis. We extracted the data for VOD episodes, graft vs host disease (GVHD) episodes and survival after stem cell transplantation. We excluded case reports, preclinical trials, review articles, meta-analysis, and trials not providing any information about the above-mentioned. We used the R programming language (version 4.0.2) to conduct a meta-analysis. Results: Total number of patients tested was 356 in thrombomodulin group and 494 in control group. The age range was 16 to 74 years. Thrombomodulin group had 254 males and control group had 190 (Table 1.). For VOD, risk ratio (RR) was 0.53 (I2= 0%, 95% CI=0.32-0.89) in favor of rTM vs heparin or no therapy for prevention of VOD after stem cell transplantation (Fig 1.). rTM was effective in prevention of transplant-associated thrombotic microangiopathy (TA-TMA) after HSCT. RR was 0.48 (I2= 62%, 95% CI=0.20-1.17) with significant lower incidence of TMA in rTM group (Fig 2.). In a trial, seven of nine patients recovered from TA-TMA in the rTM group, but none recovered in the control group who received various therapies including fresh frozen plasma, therapeutic plasma exchange(TPE) or others (p=0.003) (Fujiwara et al). The risk of GVHD was also significantly lower in rTM group and RR was 0.48 (I2= 64%, 95% CI=0.32-0.72) which again favours rTM vs heparin or no therapy (Fig 3.). Ishii et al showed that stepwise multivariate logistic regression analyses revealed that anti-coagulation therapy without rTM was an independent risk factor for aGVHD (p=0.000, odds ratio=3.006) and VOD (p=0.015, odds ratio=2.65). Yakushijin et al compared rTM with Defibrotide and found similar complete remission (CR) rate and the overall survival (OS) at day 100 in both the groups. Therefore, rhTM could be one of the potential novel candidate for SOS treatment. Use of rTM improved the survival rate of patients with disseminated intravascular coagulation (DIC), diagnosed according to the criteria established by the Ministry of Health, Labor and Welfare of Japan, at day 100 (83% vs. 50%, P = 0.026) and significantly prolonged the OS of these patients (P = 0.044). The Kaplan-Meier curves clearly showed the improved non-relapse-related mortality of patients who received rTM after HSCT (Ikezoe et al). Mean DIC scores improved significantly with the use of rhTM (p = 0.003; DIC withdrawal rate 91.7%). FDP and CRP levels were also significantly decreased (p = 0.042 and p = 0.001). The recovery rate from DIC at 28 days was significantly better in rTM than in antithrombin or heparin group (p = 0.011) (Inoue et al). The mean peak plasminogen activator inhibitor type one (PAI- 1) level was significantly lower in the rTM group vs heparin and ursodiol group (P = 0.04), and the mean peak activated protein C (APC) level was significantly higher in the rTM group (P = 0.01) (Yamamoto et al). No serious grade 3 or 4 adverse events were reported by trials. Conclusion: This systematic review and meta-analysis shows that prophylactic rTM (380 units/kg) has a beneficial role in the prevention of post- HSCT SOS complication in patients that are at high risk of developing the condition. It appears to help improve treatment-related mortality and overcome the poor survival rates. Additional randomized clinical trials are needed to establish efficacy and safety of rTM to prevent VOD and to confirm these results. Disclosures Anwer: Celgene: Research Funding; Millennium Pharmaceuticals: Research Funding; Astellas Pharma: Research Funding; Acetylon Pharmaceuticals: Research Funding; Seattle Genetics: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau; AbbVie Pharmaceuticals: Research Funding; Incyte Pharmaceuticals: Consultancy, Honoraria, Other: Travel, Accommodations, Expenses, Speakers Bureau.

Introduction: Light chain amyloidosis (AL) is a plasma cell disorder associated with detrimental manifestations in multiple organ systems of the body. It is estimated that approximately 1275-3200 new cases occur in the United States annually. Proteasome inhibitors (PI), such as bortezomib, carfilzomib, and ixazomib used for multiple myeloma treatment are also used for the treatment of AL amyloidosis. Our aim in this review is to evaluate the efficacy and safety profile of PI-based regimens for the treatment of newly diagnosed AL Amyloidosis (ND-AL). Methods: We conducted a systematic review (following PRISMA guidelines) by completing a comprehensive literature search on PubMed, Cochrane, ClinicalTrials.gov, and Embase on June 23rd, 2020. We were able to identify 901 articles, 325 articles from PubMed, 50 from Cochrane, 23 from Clinical Trials.org, and 253 from Embase. After the screening, we selected 11 published studies (n=436) including 5 phase lll trials, 2 phase I/II trials. Results: Cyclophosphamide, Bortezomib, Dexamethasone (CyBorD) with or without Daratumumab (Dara): In a Phase lll trial (ANDEROMADA study), Palldini et al. (2020) studied the efficacy of Dara+ CyBorD vs CyBorD in ND-AL pts (n=28). The addition of Dara to CyBorD showed an improved overall hematological response (ORR) in 96% with complete response (CR) in 54% pts at a median follow up of 17.6 months (Table 1). In a retrospective study by Lim et al. (2017), CyBorD was given to ND-AL pts (n=39) which showed an ORR in 63% with very good partial response (VGPR) in 50% pts. In a retrospective study by Diaz-Pallares et al. (2020), CyBord was given to ND-AL pts (n=34) which showed an ORR in 91% with CR, VGPR, and partial response (PR) in 26%, 26%, and 38% pts, respectively. Progression-free survival (PFS) and overall survival (OS) were reported at 26.7 months and 22 months (P=0.06) respectively (Table 1). Bortezomib, Melphalan, Dexamethasone (BMD): In a phase III trial (EMN-03 study), Kastritis et al. (2020) studied the efficacy of BMD vs MD in ND-AL pts (n=109). Addition of B to MD showed an improved ORR: 81% vs 56% (p=0.001) with CR/VGPR in 53% vs 28% pts. No significant difference in survival outcome was observed. In a phase III trial, Kastritis et al. (2015) studied the efficacy of BMD vs MD in ND-AL pts (n=69). Addition of B to MD showed an improved ORR: 75% vs 53% (p=0.075) with CR/VGPR in 56% vs 42% pts (p=0.277). OS and PFS were also improved in BMD group as compared to control group: 83% vs 72% (p= 0.295) and 61% vs 49% (p=0.079) at 2 years, respectively (Table 1). Bortezomib, Melphalan, Prednisolone (BMP): In a retrospective study by Lee et al. (2014), BMP was given to ND-AL pts (n=19) which showed an ORR in 84% pts with CR, VGPR and PR in 37%, 21% and 26% pts, respectively (Table 1). Induction with B based regimens for ASCT: In a Phase lll trial (HOVON 104), Minnema et al. (2019), studied the efficacy of BD induction prior to HDM/ASCT in pts (n=35) with ND-AL. At 6 months, BD induction prior to HDM/ASCT vs No BD Induction prior to HDM/ASCT showed an ORR: 80% vs 80% with an improved CR: 43% vs 5% and VGPR: 54% vs 51%. In a Phase I/II trial by Sanchorawala et al. (2015), BD induction followed by B-HDM conditioning for ASCT was done in pts (n=27) with ND-AL. ORR at 6 months post ASCT was observed in 100% pts with CR and VGPR in 63% and 37% pts, respectively (Table 1). Induction with B based regimen prior to ASCT vs Upfront ASCT: In a retrospective analysis by Scharman et al. (2017), 53 pts who received ASCT were categorized into 3 groups i.e. Upfront ASCT, induction with B based regimen and induction with other regimens. ND-AL Patients (n=34/53) receiving B based induction vs no induction showed an improved ORR: 94% vs 69% (p=0.04). OS also improved in B based induction as compared to no induction group: 87% vs 77% (p=0.22) at 3 years. PFS at 3 years was 61% vs 69%, respectively (Table 1). Conclusions: PI-based regimens have shown favorable outcomes in the treatment of ND-AL and are effective therapeutic options. The most promising results are observed with CyBorD+Dara. The adverse events associated with PI-based therapy are peripheral neuropathy, anemia, thrombocytopenia, and infections. Further prospective clinical trials are warranted for a broader understanding of the safety and efficacy profile of PI-based regimens and correlation with individual pts characteristics. Table Caption: Table 1: Comparative efficacy and safety of proteasome-inhibitor based drug regimens in ND-AL Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Introduction: Primary CNS lymphoma (PCNSL) is a highly aggressive non-Hodgkin lymphoma (NHL) variant limited to the CNS with rare evidence of systemic spread. It constitutes 4% of all CNS malignancies. Owing to the impenetrable blood-brain barrier to routine chemo-immunotherapy, the efficacy of such treatment is less than optimal. The combination of chemoradiotherapy has substantial associated risk of late neurotoxicity and increased disease recurrence. High dose chemotherapy (HDT) with autologous stem cell transplantation (ASCT) as rescue has been shown to be effective. We performed a systematic review of literature to explore the efficacy of HDT and ASCT in patients with PCNSL. Methods: We performed a comprehensive literature search (following PRISMA guidelines) on May 28, 2020 on Pubmed, Cochrane Library and Clinicaltrials.Gov by using the MeSH terms related to high-dose chemotherapy, autologous transplantation and primary CNS lymphoma which yielded 561 relevant articles. Following subsequent screening by 2 reviewers, we selected 16 published trials (n=745) and included data from these studies in our systematic review. We manually extracted data summarized the results. Results: 405/745 patients eventually underwent sequential HDT+ASCT the results of which are illustrated in table 1 and 2 stratified on the basis of newly diagnosed (ND) (n=641) and relapsed, refractory (RR) PCNSL patients (n=104) respectively. ND PCNSL: Among ND PCNSL patients, carmustine and thiotepa based regimens were the most widely studied HDT regimens (n= 351). Illerhaus et al. (2016, n= 81) in a phase 2 trial used HDT of intravenous (IV) combinations of rituximab, thiotepa and carmustine followed by ASCT on 73 patients which yielded partial response (PR) 13.9 %, complete response (CR) 77.2% and overall survival (OS) 81% at 36 months. 4 patients suffered transplant related mortality (TRM), mucositis (8%) and arrhythmias (2%) were the most common nonhematologic >grade 4 adverse effects. Ferreri et al. (2017) [n=122] in a phase 2 trial (n=59) used ASCT following Carmustine + Thiotepa HDT and reported 2-year OS of 71% and CR of 93% with a modest toxicity profile (infections (8%), mucositis (5%) and 2 (3%) treatment related deaths). IV thiotepa, busulfan and cyclophosphamide (TBC) combination was used as HDT / ASCT in ND PCNSL patients (n=208). Omuro et al. (2015) (n=32) used HDT with TBC followed by ASCT in 26 patients. Whole brain radiation therapy (WBRT) was not given to any patient regardless of recurrence or relapse. At 5 years, the study reported PR=11%, CR=81%, and OS=81%. In a phase 2 trial, Houillier et al. (2019, n=140) used TBC combination as HDT followed by either WBRT or ASCT (2 separate arms), 44 patients of the latter arm exhibited a CR of 38% and OS of 66% at 5 years with 5 treatment related deaths. An IV combinations of carmustine, etoposide, cytarabine and melphalan (BEAM) have also been used as HDT with ASCT in 3 phase 2 trials (n=59). Abrey et al. (2003, n=28) in a phase 2 trial used high-dose BEAM therapy followed by ASCT which yielded PR of 14%, CR of 57% and OS of 55% at 28 months. Only 1 treatment related mortality occurred. RR PCNSL: TBC combination has been the most extensively used HDT regimen for RR PCNSL patients undergoing ASCT (n=65). Soussain et al. (2008, n=43) conducted a phase 2 trial in which high-dose TBC sequentially followed by ASCT was studied in 27 RR PCNSL patients. The results showed median PFS of 41.1 months with OS of 45% at 2 years however, 3 toxicity related deaths were observed. Kasenda et al. (2017, n=39) in a phase 2 trial used high-dose combination of rituximab, carmustine and thiotepa coupled with ASCT on RR PCNSL patients which yielded PR of 15.4%, CR of 56% and median PFS of 12.4 months with an OS of 56.4% at 2 years. However, there were 4 treatment related deaths and an extensive toxicity spectrum with widespread pancytopenia (thrombocytopenia =96.9%, leukopenia =100%, anemia =65.6%) and nonhematologic infections (65.6%) observed. Conclusion: HDT followed by ASCT rescue has exhibited favorable outcomes and can be used an alternative to WBRT especially in ND PCNSL patients. Evidence is limited by mainly phase II non randomized data. Although, hematologic adverse effects due to HDT were observed on a widespread basis, transplant related mortality was however minimal. There is need to carry out prospective randomized phase III trials to access the safety and efficacy profile of HDT / ASCT for ND and RR PCNSL. Table Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Background: Philadelphia negative myeloproliferative neoplasms (MPNs) include polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF). MPNs can progress to accelerated and blast phase (MPN-AP/BP), defined by blast percentage of 10-19% and ≥20%, respectively, based on IWG-MRT. The therapeutic options, aside from allogeneic hematopoietic stem cell transplantation (Allo-HSCT), are limited. Hypomethylating agents (HMAs), including azacitidine (5-aza) and decitabine, are an effective treatment option for myelodysplastic syndrome and acute myeloid leukemia (AML). They have been used for older adults who are ineligible for intensive chemotherapy. Herein, we did a systematic review to evaluate the efficacy and toxicity of HMAs in MPN-AP/BP. Methods We comprehensively searched multiple databases (PubMed, google scholar, EMBASE, and clinicaltrials.gov), from the inception of the database until April 2020. We used MeSH terms and keywords related to azacitidine, decitabine, and MPN-AP/BP. We included studies that used HMAs as monotherapy on in combination to treat Philadelphia negative MPNs AP/BP and were published in the English language. The initial search yielded 2439 articles. After screening by two reviewers and excluding irrelevant articles, 16 studies were explored in detail. Results Of those studies, nine articles looked at HMAs as monotherapy (five articles for 5-aza and four articles for decitabine). The remaining articles looked at different combinations, including decitabine and ruxolitinib in four studies, 5-aza and ruxolitinib in one study, and ruxolitinib with either decitabine or 5-aza in one study. The combined overall response rate of the 5-aza monotherapy trials was 52/91 (57%), complete response rate (CR) was 26/118 (22.0%), partial response (PR) was 15/118 (12.7%), and hematological improvement (HI) was 18/118 (15.2%). The median overall survival (OS) ranged from 8.4-13.5 months. The combination of 5-aza and ruxolitinib was reported by Drummond et al. with ORR, CR, and PR of 33%, 16.6%, and 16.6%, respectively. Hobbs et al. reported that 1/8 patients receiving HMA (unspecified) achieved CR or CR with incomplete platelet recovery. Four studies reported the use of decitabine alone for the treatment of MPN-AP/BP. Three out of the four studies reported the response rate, and the combined ORR based on these studies was 14/29 (48.3%), CR was 6/42 (14.3%), and PR was 6/41 (14.6%), while the median OS ranged from 6.9 to 9.7 months. The fourth study published by Mascarenhas et al. reported outcomes of decitabine in 6 patients with MF-BP. Three out of six patients treated with decitabine died at 5, 7, and 10 months. The combined ORR of the four studies of the combination decitabine and ruxolitinib was 22/46 (47.8%), CR was 8/67 (11.9%), and PR was 6/46 (13.0%), while median OS ranged from 6.9 months to 21 months. Lancman et al. reported a CR rate of 15% with the use of ruxolitinib with either decitabine (n=26) or 5-aza (n=1). The most common hematological adverse effects reported were thrombocytopenia, neutropenia, anemia, and lymphopenia. The significant non-hematological adverse events were gastrointestinal intolerance (nausea, vomiting, and diarrhea), hypokalemia, and injection site reaction, in addition to infections and bleeding. Conclusion All evidence available for the use of HMAs in Philadelphia negative MPNs-AP/BP is from small series and retrospective analysis. Although they are well tolerated as monotherapy and in combination with other agents like ruxolitinib, they have low CR rates (up to 22% only). The tolerability profile along with familiarity with the drug makes them an attractive option. More effective treatment options with reasonable toxicity profile remain an unmet need in the elderly or frail and unfit patients, who are ineligible for induction chemotherapy and Allo-HSCT. Prospective larger-scale studies are warranted to evaluate the efficacy of HMAs, preferably in combination with novel agents, to achieve higher remission rates with minimal toxicity. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau. Fazal:Celgene: Speakers Bureau; Karyopham: Speakers Bureau; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Agios: Consultancy, Speakers Bureau; Glaxosmith Kline: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Stemline: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau; Jansen: Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Introduction: With progressive aging of the worldwide population, the number of newly diagnosed multiple myeloma (NDMM) cases are anticipated to escalate. Disease management for elderly, frail, and transplant-ineligible patients still remains a challenge. With our systematic review, we plan to summarize the available therapeutic options for frail, elderly, and transplant-ineligible NDMM patients. Methods: A comprehensive literature search was performed on May 27, 2020 on PubMed, Cochrane Library, and ClinicalTrials.gov. The search was not limited to any geographical area, date, or language. The keywords used in the search were: newly diagnosed, multiple myeloma, frail, elderly, transplant-ineligible, and treatment outcome. After subsequent screening, following the PRISMA guidelines, 24 ongoing/completed studies (n= 10,095) were included in the review. Results: Two and three drug combination regimens: Among the two and three drug combinations (see tables 1 and 2), lenalidomide (R) and dexamethasone (d) (Rd) combination (n=1445) and bortezomib (V), melphalan (M) and prednisone (P) (VMP) combination (n=1059) have been the most extensively studied combinations thus far. In a phase 2 trial, Takezako et al. (2016) used 9 cycles of VMP followed by bortezomib maintenance exclusively in frail patients, which yielded an ORR of 87%, CR rate of 25%, and PFS of 36 months. The addition of bortezomib (V) to Rd (VRd) was also studied in a phase 3 (SWOG S0777) trial by Durie et al. (2017) (n=471) in transplant-ineligible patients, which showed superior therapeutic response rates (PFS 43 months, OS of 75 months, and ORR of 82%) in the VRd group compared to Rd (PFS of 30 months, OS of 64 months and ORR of 72%) alone. However, the three-drug combination of daratumumab (Dara)+Rd has overall shown the best treatment results (ORR 92.9%, CR 47.6% and VGPR 31.8%) as evidenced by Facon et. al (2019) (n=368). Although, when compared to Rd, Dara-Rd was associated with more neutropenia (50% versus 35.3%); however, Dara-Rd had an overall lower incidence of infections (32.1% versus 73.4%) and hence, lower discontinuation rate (32.4% versus 56.7%) when compared to Rd, respectively. Four or five drug combination regimens: Four and five drug combinations have been studied in two phase II/III trials (n=933) in transplant-ineligible patients. A phase two trial (Mateos, 2015) studying VMPRd in frail patients resulted in an ORR of 68%, CR 20%, and PFS of 25 months after 35 days of VMPRd induction, followed by dose de-escalation to twice monthly bortezomib-only maintenance until disease progression. Dara-VMP was compared with VMP alone in a phase 3 trial (Mateos, 2017) (n=700), in which 9 cycles of Dara-VMP (42 days each) were de-escalated to daratumumab-only maintenance. Thisshowed superior results in Dara-VMP (ORR 90.9% versus 73.9%, CR 42.6% versus 24.4%, and PFS was not reached in Dara-VMP group versus 18.1 months) compared to the VMP group. Moreover, this dose de-escalation also seemed to improve treatment tolerability, as the discontinuation rate due to adverse effects was also lower (4.9%). Currently, various trials are ongoing to explore the connection between frailty status and associated treatment outcomes (table 3). Conclusion: Combination regimens, including agents like daratumumab and bortezomib, have exhibited promising results both in terms of superior efficacy and reduced adverse effects profiles. In addition, dose de-escalated maintenance therapies following induction therapies based on multidrug combinations have exhibited noteworthy success, with comparable efficacy and reduced toxicity rates in frail and transplant-ineligible NDMM patients. However, there remains an opportunity to further tailor the dose and type of drug combinations on a 'frailty-adjusted' basis, with trials designed around this risk stratification providing the highest quality data. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Introduction: Despite multiple treatment options, multiple myeloma (MM) remains an incurable disease. Chimeric antigen receptor T-cell (CAR T) therapy, a form of adoptive immunotherapy, has shown favorable outcomes in the treatment of hematological malignancies. The B cell maturation antigen (BCMA) which is present on myeloma cells, serves as a valid target site for CAR T cells. Early studies have shown promising outcomes in patients (pts) with relapsed and refractory MM (RRMM). However, CAR T therapy is also associated with multiple adverse effects. The main objective of this review is to evaluate the all grades of CRS and other commonly occurring adverse events (AE) associated with CAR T therapy in pts with RRMM. Methods: A systematic search of databases (following PRISMA guidelines) PubMed, Cochrane, Embase and, clinicaltrials.gov was performed with no restrictions of language and time period. A total of 249 articles were identified initially and after a detailed screening, we finalized 16 studies including 12 phase I and 3 phase Ib/II clinical trials and 1 retrospective analysis for data extraction. Results: Total included trials were 15 and trial-level data collected from 392 pts is summarized in Table 1 and Table 2. Commonly used CAR T regimens for the treatment of MM were bb2121 BCMA, P BCMA 101 CAR, LCAR B38 M, and anti CD19 CAR. Single Target; Anti BCMA CAR T (Table 1) BCMA CAR T, LCAR-B38M: In a phase I trial, Cohen et al. (2019) reported G1&2 CRS in 56% pts (n=25) and G3 CRS in 32% pts when treated with BCMA specific CAR T. Leukopenia, neutropenia, and lymphopenia were seen in 44%, 44% and 36% of pts, respectively. In a phase I trial, Wang et al. (2019) reported G1 & G2 CRS in 47% and 35% pts (n=57), respectively and G3 CRS in 7% pts when treated with LCAR-B38M CAR T. Pyrexia, thrombocytopenia, and leukopenia were seen in 90%, 49% and 30% pts, respectively. In a phase I trial, Chen et al. (2019) reported G1/2 CRS in 58% pts (n=17) and G3 and G5 CRS in 35% and 5% pts respectively when treated with LCAR-B38M. Hepatotoxicity and cytopenia were seen in 100% and 82% pts, respectively. In a phase 1 trial, Brudno et al. (2018) reported G1/2 in 56% pts (n=16) and G3 in 37% pts when treated with BCMA CAR T. Anemia, leukopenia and thrombocytopenia were observed in 68%, 62% and 43% pts, respectively. JNJ-4528, bb2121 In a phase Ib/II trial, Berdeja et al. (2020) reported G1/2 CRS in 86% pts (n=29), G3 and G4 CRS in 3.5% pts each when treated with JNJ-4528 (an LCAR-B38M) CAR T. Neutropenia, thrombocytopenia and leukopenia were seen in 100%, 69% and 59% pts, respectively. In a phase I trial, Berdeja et al. (2019) reported G1, G2 and G3 CRS in 22%, 32% and 5% pts (n=22), respectively when treated with bb2121 CAR T. Neurotoxicity was observed in 22% pts. In a phase I trial, Raje et al. (2017) reported CRS of any grade in 76% pts (n=33) and G3 CRS in 6% pts when treated with bb2121 CAR T. Neurotoxicity, hypotension and hyponatremia were observed in 42%, 15% and 15% pts, respectively. Dual Target CAR T (Table 2) Anti-CD19/BCMA, PF-3135, Dual Target BM38: In a phase Ib trial, Shi et al. (2019) reported G1/2 CRS in 97% pts (n=32) while G3/4 CRS in 3% pts when treated with anti-CD19/BCMA CAR T. Other AE were slight and reversible. In a phase I/II trial, Yan et al. (2019) reported G1/G2 CRS in 86% pts (n=21) and G3/4 CRS in 5% pts when treated with humanized anti-CD19/BCMA CAR T. Neutropenia, Anemia and thrombocytopenia were observed in 86%, 62% and 62% pts, respectively. In a phase I trial, Raje et al. (2019) reported G1/2 CRS in 24% pts (n=17) and G3 CRS in 5% pts when treated with PF-3515 (anti-CD3-BCMA) CAR T. Hepatotoxicity, thrombocytopenia, Neutropenia and pyrexia were observed in 18%, 24%, 18% and 18% pts, respectively. In a phase I trial, Li et al. (2019) reported G1/2 CRS in 62% pts (n=16) and G3 CRS in 25% pts when treated with Dual-target BM38 CAR T. No dose-limiting (>/G3) toxicities were observed at a median follow up of 36 months. Conclusion: CAR T therapy is emerging as a treatment modality for RRMM. With promising initial results, there is evidence for multiple side effects, the most concerning and common one is CRS. The most frequently occurring CRS grade is G 1&2 (requiring symptomatic treatment), but G3 CRS is also reported which can be dose-limiting and life-threatening. Neurotoxicity, hematological abnormalities, hepatotoxicity and pyrexia are the other common side effects 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.

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.

Introduction: Multiple myeloma (MM) is a hematologic malignancy in which clonal plasma cell proliferation leads to complications and death. Daratumumab (Dara) is a humanized IgGk monoclonal antibody that targets CD38- a glycoprotein expressed on plasma cells and malignant cells. Dara has direct anti-tumor effects along with immunomodulatory activities, resulting in clonal expansion of cytotoxic T cells and diminution of immunosuppressive cells. This review highlights the efficacy and safety of Dara addition to the standard of care regimen, tested in Phase III trials, in patients with relapsed refractory MM (RRMM). Methods: We conducted a systematic literature search in four databases (PubMed, Embase, Cochrane, and Clinicaltrials.gov) using MeSH terms and keywords for multiple myeloma and Dara including trade names and generic names from date of inception to April 2020. Initial search revealed 587 articles. After excluding review articles, duplicates, and non-relevant articles, we included three phase III trials reporting daratumumab addition to the standard of care regimens for RRMM patients. Results: A total of 1521 patients out of 1533 enrolled patients were evaluated in three phase III randomized controlled trials. A total of 849 patients were evaluated in the Dara group and 684 patients were evaluated in the control group. Catja. C et al. (2019) studied the role of Dara + bortezomib (V) + dexamethasone (d) in RRMM pts (n=498) in phase III trial (CASTOR). Saad Z.U et al. (2019) underlined the efficacy of Dara + carfilzomib (K) and (d) in RRMM pts (n=466) in phase III trial (CANDOR), and Nizar J. Bahlis et al. (2020) studied Dara + lenolidamide (R) + d in RRMM pts (n=569) in phase III trial (POLLUX). The addition of Dara to Vd, Rd, and Kd group was significant in term of overall response rate (ORR): 85% vs 63% (P Addition of Dara to standard care regimen (Vd and Rd) achieved superior outcomes in terms of ORR, PFS and OS, except Kd group, in which only ORR was improved as compared to control group. Combination of Dara plus standard care regimen improved MRD negative status in RRMM patients as compared to standard regimen. Conclusion: Treatment of RRMM with Dara plus standard care therapy (Vd, Rd, and Kd) has shown promising outcomes with improved efficacy and higher negative MRD status, providing a new benchmark for future studies. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celgene, Millennium Pharmaceuticals,: Honoraria, Research Funding, Speakers Bureau.

e19021 Background: Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HCT) characterized by severe multilineage cytopenia in the absence of mixed donor chimerism, relapse, or severe graft-vs-host disease (GVHD). We present a systemic review and meta-analysis aimed to assess the outcomes with stem cell boost (SCB) for PGF in adult allo-HCT patients. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, 752 articles were screened from 4 databases (PubMed, Embase, Cochrane, and Clinical trials.gov) using MeSH terms and keywords for “hematological malignancies”, “hematopoietic stem cell transplantation”, “CD34 antigen(s)” and “treatment outcome(s)” from the date of inception to Jan 2021. After excluding review, duplicate and non-relevant articles, we included 8 studies (1 prospective, 7 retrospective) reporting hematologic complete/overall response rate (CR/ORR), GVHD and overall survival (OS) after SCB for PGF after Allo-HSCT. Quality evaluation was done using the NIH quality assessment tool. Pooled analysis was done using the ‘meta’ package (Schwarzer et al, R programming language) and proportions with 95% confidence intervals (CI) were computed. Inter-study variance was calculated using Der Simonian-Laird Estimator. Results: We identified 217 patients who received SCB for PGF after allo-HCT. Median age, time since transplant and SCB dose were 48 (37-54) years, 133 (113-450) days and 3.43 (1.7-4.9) million CD34 cells/kg respectively. CR and ORR were 71% (95%CI 0.63-0.77, I216%) and 80% (95%CI 0.74-0.85, I20%) respectively. After median follow up of 41.5 (5-77) months, actuarial survival rate (ASR) was 54% (95%CI 0.48-0.61, I20%). OS was reported from 80% (1y) to 40% (9y) Acute and chronic GVHD incidence after SCB was 17% (95% CI 0.12-0.23, I2=0%) and 17% (95% CI 0.08-0.32, I2=72%, n=197) respectively, and 25% (95% CI 0.14-0.39, I2=63%, n=163) deaths were due to relapse (Table). Conclusions: CD34 SCB improves outcomes after PGF after allo-HSCT with acceptable toxicity profile. However, current literature lacks high-quality randomized evidence and there remains an unmet need for prospective studies to address optimal dosing and manipulation of SCB. Outcomes with SCB for PGF after allo-HCT (n=217).[Table: see text]

e19045 Background: Post-transplant lymphoproliferative disorder (PTLD) is a complication after liver transplantation. This study aims to explore the association of PTLD with the immunosuppression, types of PTLD, clinical presentation, and outcomes. Methods: Following the PRISMA guideline, we searched the literature on PubMed, Cochrane, Embase, and clinicaltrials.gov. 1741 articles were screened and 22 studies were included. Results: Data includes 22,235 total patients who underwent a liver transplant, and 449 (2.0%) patients who developed PTLD were studied. Of the 394 patients where gender was reported, 226 were male and 168 were female. Post-transplant EBV status was positive for 63/115 (56%). 11 studies showed that the median time from transplant to the development of PTLD was 33.4 months. Among the histological types of PTLD, the monomorphic B-cell was the most common type with 127/235 (54%) cases, followed by early lesions 25/235, polymorphic 24/235, Hodgkin lymphoma 8/235, and monomorphic T-cell type 7/235. Treatment of PTLD involved reduction or cessation of the immunosuppressive drugs along with chemotherapy surgery and radiotherapy. Mortality data from 13 studies showed 68/259 (31.3%) patients died either due to PTLD or its complication. Conclusions: PTLD is rare but associated with high mortality after liver transplantation. EBV seropositivity is associated with PTLD in the majority of cases. Monomorphic PTLD is the most common type of PTLD after liver transplantation with DLBCL being the most common subtype. Abdominal symptoms and fever are among the most common symptoms. PTLD after Liver transplant a review of studies. [Table: see text]

e20042 Background: Light-chain deposition disease (LCDD) is part of a wide spectrum of plasma cell proliferation disorders. LCDD predominantly affects kidneys by systemic deposition of congo red negative non-fibrillar light chains. Due to the rarity of disease, no prospective data is available, and clear guidelines don’t exist for the treatment. We reviewed data to summarize effective treatment strategies. Methods: A literature search was conducted on PubMed, Cochrane, and ClinicalTrials.gov with final update in November 2020 using terms ‘light chain deposition disease’, ‘therapy,’ and ‘disease management’. Library was manually screened to remove articles on LCDD in transplant kidneys. We identified 63 case reports/series and 11 retrospective studies n=365. Results: Retrospective Studies: 9 studies (n=283) identified various combinations of LCDD and plasma cell dyscrasias given the rarity of idiopathic LCDD. Lorenz et al. reported 6 patients (pts) that received ASCT with MEL preconditioning with 92% improved proteinuria and 95% improved eGFR. Pozzi et al. reported 63 pts (32% idiopathic LCDD, 65% concurrent MM and 3% concurrent CLL) where all pts received a combination of vincristine, doxorubicin, dexamethasone/methylprednisolone. 5/63 patients received ASCT. The median survival was 4.1 years. Bortezomib (V) based regimens: Most experts favor V based regimens to treat LCDD, but no dedicated trials exist. 26 case reports/case series (37 pts) included; 23 pts with idiopathic LCDD and rest with a concurrent disorder. Daratumumab: Milani et al. treated 8 pts with LCDD and concurrent MM with single agent daratumumab who failed at least one regimen. Autologous stem cell transplant (ASCT): 13 case reports/case series (20 pts) identified who received ASCT with melphalan (MEL) conditioning with/without various combinations of chemotherapies before and after ASCT. 14 pts had LCDD, and 6 pts had concurrent clonal cell dyscrasia. Miscellaneous regimens: Various other regimens showed promising results with improved renal functions but not well studied e.g., thalidomide and dexamethasone (Haruyuki et al.). Conclusions: Dedicated clinical trials are difficult given rarity of LCDD but needed. Bortezomib based regimens seem to be good options, ASCT with MEL conditioning is a suitable choice for younger and fit pts.[Table: see text]

e19046 Background: Post-transplant lymphoproliferative disorder (PTLD) is a serious complication after solid organ transplantation. This study aims to explore the association of PTLD diagnosed after lung transplant with infectious agents and immunosuppression regimen, explore types of PTLD, and their outcome. Methods: Following the PRISMA guideline, we searched the literature on PubMed, Cochrane, Embase, and clinicaltrials.gov. 1741 articles were screened and included five studies. Results: We analyzed data from five studies, n=13,643 transplant recipients with n=287 (2.10%) developed PTLD. Four studies showed that 32/63 (51%) PTLD patients were male and 31 (49%) were female. Three studies reported 53/55 (96.4%) patients were EBV positive at PTLD diagnosis. Courtwright. et al, reported that 217/224 (97%) PTLD was associated with either EBV positive donor or recipient. Four studies showed that the monomorphic B cell type 48/63 (76%) was the most common histological type of PTLD diagnosed with DLBCL the most common subtype 31/48 (64.6%). Data from 3 studies showed that the onset of PTLD following lung transplant varies with a median duration of 18.3 months (45 days to 20.2 years). Three studies showed that 26/55 (47.3%) patients had early-onset (≤ 1 yr of Tx) and 29/55 (52.7%) patients had late-onset PTLD (> 1 yr of Tx). Management of PTLD included a reduction in immunosuppression including corticosteroids, CNI, purine synthesis inhibitors, Rituximab, and chemotherapeutic agents. Three studies showed a mortality rate of 30/45 (66.7%) and 13/30 (43.3%) deaths were PTLD related. Conclusions: Our review concludes that PTLD is a serious complication, only 2% of lung transplant recipients developed PTLD. EBV seropositivity is the most factor associated with PTLD diagnosis. Monomorphic PTLD was reported as the most common type in the adult population and no association between gender and PTLD was found. The analysis shows that there is a slightly lower incidence of early (≤ 1 yr of Tx) than late-onset (> 1 yr of Tx) PTLD. Table 1 PTLD after a Lung transplant in adults - a review. [Table: see text]

e20014 Background: Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of relapsed/refractory multiple myeloma on July 2019 and August 2020 respectively. The toxicity profile of these drugs is a concern since these are approved for use in patients who have already undergone multiple lines of treatment. Methods: Six studies for Sel and two for belamaf were included after a systematic search of PubMed, Embase, Cochrane, and Clinicaltrials.gov. Results: The most common hematological toxicity associated with these two drugs is thrombocytopenia. The common G-3/4 hematological AEs of Sel were thrombocytopenia (39%-71%), anemia (16%-33%), leukopenia (8%-33%) and neutropenia (9%-33%) whereas common G-3/4 non-hematological AEs were hyponatremia (5%-26%), fatigue (13%-15%), diarrhea (5%-10%), eye disorders (9%-10%), musculoskeletal disorders (4%-10%), elevated liver enzymes (10%), peripheral neuropathy (5%) and vomiting (2-4%). Keratopathy and anemia were the major toxicities of belamaf. Most of these toxicities are manageable. Treatment modifications and dose interruption are usually needed when AEs are more than grade II. REMS program guidelines is recommended for close monitoring and evaluation of Sel and belamaf toxicities and early ophthalmological intervention. Conclusions: As these are newer drugs with limited data, continuous surveillance and monitoring is warranted during the treatment course with early mitigation strategies. The physician should be aware of thrombocytopenia and its management as well as belamaf ocular toxicity which is manageable but if missed could have serious complications.[Table: see text]

Introduction: Daratumumab (Dara) is a human anti-CD38 monoclonal antibody approved for multiple myeloma (MM) treatment. Dara has shown promising efficacy and a favorable safety profile in newly diagnosed (ND) and relapsed refractory MM patients. This study is focused on the efficacy and safety of Dara when added to the standard care regimen in transplant eligible newly diagnosed MM (NDMM) in phase III clinical trials. Methods: We performed a comprehensive literature search on four databases (PubMed, Embase, Cochrane, and Clinicaltrials.gov). Our search strategy included MeSH (Medical Subject Headings) terms and keywords for multiple myeloma and Dara including trade names and generic names from date of inception to May 2020. Initial search revealed 588 articles. After a detailed screening, two phase III randomized clinical trials were included, which reported overall response rate (ORR) and negative minimal residual disease (MRD) in transplant eligible MM patients with Dara addition to standard care regimen. Odds ratios (OR) of ORR and MRD were computed along with 95% confidence intervals (CI) for pooled analysis using a fixed-effect model in RevMan v.5.4. Results: A total of 1292 transplant eligible NDMM patients were enrolled and evaluated in two phase III randomized controlled trials. Six hundred and forty-seven patients were in the Dara group and 645 patients were in the control group. Moreau et al. (2019) studied the efficacy of Dara + bortezomib (V) + thalidomide (T) + dexamethasone (d) vs VTd in NDMM pts (n=1085) in CASSIOPEIA phase III trial. Vorhees et al. reported efficacy of Dara addition to lenalidomide (R), and Vd vs RVd in GRIFFIN study in transplant eligible NDMM patients (n= 207). Dara dose was 16 mg/kg in both studies and the median follow-up was 18.8 months and 22.1 months in CASSIOPEIA and GRIFFIN trial, respectively. A pooled analysis of these trials showed ORR (OR: 1.73, 95% CI 1.16-2.59; p < 0.008, I2 = 80%). Achievement of MRD negative status was significant in Dara based regimen as compared to control group (OR: 2.47, 95% CI 1.97-3.10; p < 0.00001, I2 = 66%). Dara addition to standard care regimen (Rd and VMP) also decreased the risk of progressive disease (OR: 0.74, 95% CI 0.43-1.28; p < 0.28, I2 = 0%). However, Dara based regimens increased the risk of neutropenia (OR: 3.41, 95% CI 2.68-4.33; p < 0.00001, I2 = 91%), and lymphopenia (OR: 3.43, 95% CI 2.71-4.34; p < 0.0001, I2 = 94%), and pyrexia (OR: 1.42 95% CI 1.11-1.82: p < 0.005, I2=50%) (Figure 1). Conclusion: Addition of Dara to the standard care regimen (VRd, VTd) for transplant eligible NDMM achieved the surrogate endpoints with improved efficacy and MRD negative status with manageable toxicity. However, data from more randomized controlled trials are needed. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

Introduction: In multiple myeloma (MM), plasma cells including malignant cells show expression of CD38, which is the target for daratumumab (Dara), an IgG1k monoclonal antibody, approved for MM treatment. This review highlights the efficacy and safety of Dara addition to the standard of care therapy in newly diagnosed MM (NDMM) patients (pts). Methods: We conducted a literature search using four databases (PubMed, Embase, Web of Science, and Clinicaltrials.gov). Our search strategy included MeSH terms and key words for multiple myeloma and Dara including trade names and generic names from date of inception to April 2020. A total of 587 articles were screened, and after excluding review articles, duplicates, and non-relevant articles, we included three phase III trials reporting daratumumab addition to the standard of care regimens for NDMM patients. Results: A total of 2528 patients were enrolled and evaluated in three phase III randomized controlled trials. A total of 1261 patients were in the daratumumab group and 1267 patients were in the control group. Total 1085 were transplant eligible and 1443 patients were transplant ineligible. Transplant eligible: Moreau et al. (2019) underlined the efficacy of Dara + bortezomib (V) + thalidomide (T) + dexamethasone (d) in NDMM pts (n=1085) in CASSIOPEIA phase III trial. Addition of Dara to VTd group showed marked improvent in progression free survival (PFS): 93% vs 85% at 18 months (hazard ratio (HR) 0.42 [0.34-0.51]; p Bahlis N et al. (2019) studied Dara + lenolidamide (R) and dexamethasone (d) in NDMM pts (n=737) in MAIA phase III trial. Mateos et al. (2018) reported the role of Dara + V + melphalan (M) + prednisone (P) vs VMP in NDMM pts (n=706) in a phase III trial (Alcyone). Addition of Dara to Rd, and VMP group showed marked improvent in PFS: 68% vs 46% at 36 months [confidence interval [CI], 0.44-0.71; P Significant toxicities mainly included pancytopenias and opportunistic infections (table 2). Standard care regimen (VTd, VMP, Rd) with Dara addition achieved superior outcomes in terms of ORR and PFS. Addition of Dara improved MRD negative status. Conclusion: NDMM treatment with Dara plus standard care therapy (VTd, VMP, Rd) has shown promising outcomes and has set a benchmark for future studies. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

2562 Background: High dose chemotherapy (HDCT) followed by autologous stem cell transplant (ASCT) has shown to overcome intrinsic chemo-resistance and improve disease control in Primary Central Nervous System Lymphoma (PCNSL). Our study reviews the treatment outcome in PCNSL with sequential HDCT and ASCT. Methods: 8/34 studies were finalized after systematic search of PubMed, Cochrane, and Clinicaltrials.gov for treatment of PCNSL with HDCT followed by ASCT. Results: 251/288 patients were evaluated. Mean age was 55.5 years. 227 underwent HDCT-ASCT. 174 were newly diagnosed (ND) and 77 had relapsed refractory (R/R) PCNSL. ND patients showed superior outcomes in terms of progression free survival and overall survival. Combinations of High dose Rituximab, Busulfan and Cyclophosphamide significantly improved survival outcomes in RR patients. Significant toxicities mainly included pancytopenias and opportunistic. Conclusions: Primary CNS lymphoma treated with HDCT followed by ASCT has shown promising outcomes and has set a benchmark for future studies. [Table: see text]