Introduction Bispecific T-cell engager (BiTE) antibodies represent a novel therapeutic option for patients with multiple myeloma (MM). BiTE antibodies lack Fc region, and have variable domain only, they can simultaneously bind to two different epitopes i.e. cluster of differentiation 3 (CD3) molecules on tumor-specific T cells, and a specific antigen on myeloma cells, which leads to T-cell dependent destruction of myeloma cells. Currently, blinatumomab, specific for CD3 and CD19 is the only Food and Drug Administration FDA approved BiTE antibody for clinical use in patients with relapsed/refractory (RR) B-cell acute lymphoblastic leukemia, several similar BiTE antibodies are under development. Methods Following PRISMA guidelines, we performed comprehensive literature on 4/15/19 cross-referencing the terms "bispecific antibodies" and "multiple myeloma" using PubMed, Embase, Web of Science, Cochrane Library, Clinicaltrials.gov and review of international medical meeting abstracts. Initially, 256 articles were identified and after detailed scrutiny, one phase 1 clinical trial with prelim results, 4 preclinical and 4 ongoing clinical trials were included. Results Preclinical trials: Anti-BCMA x Anti-CD3 Bispecific Antibody: BiTE antibodies are still in early development in MM, and most of the published data is about the pre-clinical phase. In preclinical trials, Hipp et al. 2017 and Cho et al. 2018 reported that AMG 420 (BI 836909) and AMG 701, which are anti CD3 and B-cell maturation antigen (BCMA), are highly efficacious in vitro in the killing of myeloma cells and potently induces autologous tumor cell lysis in patients with both newly diagnosed and RRMM regardless of their disease status. In mouse xenograft models reconstituted with human T cells, in vivo efficacy of AMG 420 was reported with an overall response in 6 of 10 animals, with all 6 responders became tumor-free at the end of the study. In an orthotopic L-363 xenograft model, treatment with AMG 420 resulted in prolonged median survival of 43-43.5 days. Dilillo et al. 2018 and Ji Li et al. 2017 reported similar in vivo results for REGN5458 and BFCR4350A respectively. Clinical trials: Currently, there are 5 phase 1 ongoing clinical trials (Table 1). Updated results of only first in human phase I AMG 420 are available. Forty-two MM patients with a high tumor burden and four prior lines of therapy were given 2.5 treatment cycles with AMG 420. Overall thirteen (31%) patients responded to AMG 420 therapy, with complete response (CR) in 6 (14.2%) patients, very good partial response (VGPR) in 2 (5%) patients and partial response (PR) in 2(5%) patients. Eleven of these patients responded in the first treatment cycle, with a median response time of 1 month. Twenty-five (57.1%) patients discontinued treatment due to progressive disease. Four deaths were reported; 2 from disease progression and 2 due to adverse events; neither of them was treatment-related. Serious adverse events were reported in twenty-one (50%) patients, the infection was reported in twelve (29%) and polyneuropathy in three (7%), eighteen (43%) required hospitalization. Treatment-related serious adverse events included three (7%) patients with grade 2-3 cytokine release syndrome, three (7%) with polyneuropathy and one (2.3%) with edema. Conclusion After the success of naked antibodies like daratumumab and elotuzumab for MM, there is a need to develop immunotherapy using conjugated antibodies and BiTE antibodies to overcome the challenge of MM resistance and relapse to prior therapies. Preclinical data with BiTE antibodies are promising; AMG 420 anti-CD3/BCMA BiTE has already been granted fast track status by the FDA. We anticipate that drug will enter phase 2 clinical trials for drug development against RRMM Other BiTE antibodies with strong preclinical efficacy are under development and data from larger prospective clinical trials is needed to explore their efficacy in the treatment of multiple myeloma. Table 1 Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.

Introduction: Chimeric antigen receptor t cells (CAR T) therapy is an innovative adoptive immunotherapy being used for the treatment of CD19+ive B cell hematological malignancies, especially B cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin's lymphomas (NHL) and chronic lymphocytic Leukemia (CLL). This treatment holds the potential to be highly effective and potentially less toxic alternative to cytotoxic chemotherapy for patients with relapsed and refractory (R/R) disease.This therapeutic modality is associated with a variety of side effects which includes cytokine release syndrome (CRS), neurotoxicity, B cell aplasia, hypogammaglobulinemia and resultant high risk infections. There is paucity of data about infection related complications with CAR-T therapy. In this review, we focus on the infections associated with B cell targeting CART cell therapy for the treatment of hematological malignancies. Methods: We conducted a systematic review (following PRISMA guidelines) by completing a comprehensive PubMed, Cochrane Library and ClinicalTrials.gov search on May 15th2019. Our search strategy included using search and MeSH terms related to CAR T therapy, hematological malignancies, Infections, safety and mortality. We were able to identify 279 articles from PubMed, 26 from Cochrane, 5 from Clinical Trials.org and 7 from Web of Science. After screening we selected 13 prospective published trials (n=555) for data extraction. We manually extracted data and summarized our results. RESULTS: Total included trials were 13, and trial level data from 555 patient was summarized in Table 1. Commonly used targets were CD19 ( B cell malignancies), and BCMA (Multiple Myeloma). CAR T were used for the treatment of diseases B-cell acute lymphoblastic leukemia ( ALL), B cell NHL, CLL, and Multiple myeloma (MM). Out of the available data, the two most frequent infections were upper respiratory tract infections (RTI) and blood stream infections. Other infections observed were the lower RTI, urinary tract infections (UTI), clostridium difficile (C. Diff), meningitis, mucocutaneous herpes infections, cellulitis, mucormycosis, and aspergillosis. A Phase 1/2 trial (NCT00924326 / B-NHL / CD19 Target) demonstrated 43 cases of septicemia (23.2%), 4 cases of UTI (9.3%) and 1 case each of cellulitis (2.3%), opportunistic infections (2.3%), upper RTI and lower RTI (2.3%). Phase 1 trial (NCT01029366 / B lymphoma, leukemia / CD19 target / n=20) showed 3 cases (15%) of pneumonia, 1 case each of C Diff, Pseudomonas and salmonella (5%) infections. A Phase 2 trial (NCT02030834, B NHL, CD19 target, n=63) treated patients showed 34% patients experienced infection which included sepsis, UTI, upper and lower RTI, skin, small intestine and mucosal infections. A phase 1 trial ( NCT01840566, n=17, NHL, CD19 target) demonstrated cases of mucormycosis ( n=unknown) and 7 case of pneumonia (41.1%). In phase 2 trial (NCT02030847, B ALL, CD19, n=30) treated patients experienced cases of sepsis (10%), Pneumonia (6.7%) and 1 case each of oral Candidiasis, C Diff, influenza and meningitis (10%). A phase 1 trial (NCT01044069, n=53, RR ALL, CD19 target) showed incidence of 11 cases of blood stream infections (20.1%), 9 cases of upper RTI (16.9), 2 cases of UTI (3.8%), 2 cases of pneumonia (3.8%), 3 cases of pulmonary aspergillosis (5.7%) and a case of herpes infection (1.9). Phase 2 trial (NCT01747486, CLL, CD19, n=42) demonstrated 2 cases of sepsis (4.7%), 2 cases of influenza (4.7), 3 cases of upper respiratory tract infections (7.1%) and 2 cases of pneumonia (4.7%). NCT02215967, Phase 1 trial ( Multiple Myeloma, BCMA target, n=12) was associated with 3 cases of upper RTI (25%) and 1 case of UTI (8.3%). Table 2 summarizes additional ongoing CAR T cell trials. Conclusion: CAR T cell therapy is gaining popularity and its indications are expanding. Its complications need to be closely studied for potential infections amongst other side effects. Clinical trial results have likely under-reported infections associated with CAR-T therapy because of overlapping presentation with cytokine release syndrome (CRS), neurotoxicity and limited follow-up reported in the published trials. Additional studies with longer follow up duration are required to identify the true risk of infectious complications of CAR T therapy in patients with hematological malignancies. Real word data on CAr T patients can also reveal long term infectious complications. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: CAR-T therapy. We are summarizing infectious complications of CAR-T therapy and their projects under development.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare conditions triggered due to a medication that involves the necrosis and desquamation of the skin and mucous membranes. Only one out of 1,000,000 people are affected by the condition. The exact pathophysiology of the disease is still unknown. However, many complications of the disease can occur; pancytopenia and pleural effusion are an even rarer find. Here we present a case of a 17-year-old male who presented with fever and rash for 15 days associated with bleeding per rectum, hemoptysis, and conjunctival hemorrhages. Laboratory investigations showed severe pancytopenia, deranged liver function tests (LFTs), and hypocellular bone marrow. The patient started showing improvement after 10 days post-admission with supportive care and multiple transfusions.

Introduction: Waldenström's macroglobulinemia is a rare low-grade lymphoplasmacytic lymphoma characterized by CD20 expression on malignant cells and produces a monoclonal immunoglobulin M (IgM). Rituximab is a chimeric monoclonal antibody against CD20 antigen and the most widely used therapeutic agents in WM. Rituximab works by adhering to CD20, causes B-cell lysis mainly through antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. Cyclophosphamide is an alkylating agent binds to DNA. Its cytotoxic effect is mainly due to cross-linking of strands of DNA and RNA, and to inhibition of protein synthesis. Our objective is to analyze and summarize the published literature for the efficacy of regimens containing both rituximab and cyclophosphamide for the treatment of Waldenström's macroglobulinemia (WM). Methods:We performed a comprehensive literature search on articles following PRISMA guidelines. Beginning with articles published after January 2005, we used databases like PubMed, Embase, Clinicaltrials.gov, Cochrane Library, and Web of Science. A total of 585 articles were identified initially, and after a detailed screening, we finalized 10 studies involving 425 WM patients. Results:The total number of patients were 425. The dose was 375 mg/m2. The complete response (CR) ranged from 3-19%, very good partial response (VGPR) ranged from 4-22%, and the partial response (PR) ranged from 8-82%. The overall response rate (ORR) ranged from 79-95%. Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP): In a retrospective study by Ioakimidis et al., included 23 WM patients were given R-CHOP. The ORR was 95%, with 69% achieving a major response, 43%, PR, and VGPR OF 9%. In a randomized control trial by Buske et al., N=23, the major response rate was 91%, and PR was 82%. Treon et al. (N=13) observed a major response rate of 27%. (Table 1). Fludarabine, Cyclophosphamide and Rituximab (FCR): In a retrospective study by Peinert et al., involving 29 patients receiving the FCR regimen, the ORR was 90%, with 79%, 3%, and 10% of patients achieving PR, CR, and NR, respectively. In a study by Tedeschi et al., involving 40 patients, ORR was 80%, and the major response rate was 80%. Souchet et al., N=82 reported an ORR of 84% and a PR of 46%. Progression-free survival (PFS) was 51.2 months for Tedeschi et al. Dexamethasone, Rituximab and Cyclophosphamide (DRC) In study Paludo et al., (N=50), receiving the DRC regimen, the highest ORR was 87%, PR 64%, and major response was 68%. In a phase II study by Dimopoulos et al., (N=72), the ORR of 82% and PR of 67% was observed. PFS was 24 months in this study. (Table 1) 4.Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) In study Ioakimidis et al, N=16, the ORR was 87%, the major response rate was 62%, and the PR was 43%. Rituximab, Cyclophosphamide, and Prednisone (RCP) Ioakimidis et al., reported 19 patients who were given RCP. The ORR, PR, and the major response rate was 94%, 73%, and 73%, respectively.Lenalidomide, Rituximab, Cyclophosphamide, and Dexamethasone (LR-CD) A study by Rosenthal et al., 15 patients were given LR-CD. ORR was 80%, with a major response rate in 80% and PR in 73% of patients. PFS was 38 months. Conclusion: Rituximab and cyclophosphamide, in combination regimens for the treatment of WM showed the overall response rate of 95%. Neutropenia was the dominant side effect reported in these regimens. There is a paucity of phase 3 randomized trials demonstrating a clinical benefit of anyone regimen over another. We recommend future randomized prospective trials better to understand the efficacy and safety profile of regimens containing both rituximab and cyclophosphamide base combinations. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.:Honoraria, Research Funding, Speakers Bureau.

Introduction: Melphalan causes cross linkage between DNA, causes cytotoxicity in both dividing and non-dividing tumor cells. Our objective is to analyze and summarize the published literature for the efficacy of melphalan based regimen used for the treatment of newly diagnosed Amyloidosis (ND-AL). Methods: We performed a comprehensive literature search on articles following PRISMA guidelines. Beginning with articles published after June 2006, we used databases like PubMed, Embase, Clinicaltrials.gov, Cochrane Library and Web of Science. Total 649 articles were identified initially and after detailed screening, we finalized 10 studies involving 616 ND-AL patients. Results: Melphalan (M), Bortezomib (V) and dexamethasone (d)/prednisone (p): A retrospective study by Zhao et al., included 123 ND-AL patients (pts) were given M, V, and d. Overall hematological response (OHR) was 100% with complete response (CR) in 44% and partial response (PR) in 38.9% pts. Median overall survival (mOS) was 38 months (mo) and 3-yr survival ranged from 41-72%. Organ response (OR) was 25%. In a study by Lee et al., with 19 pts who received M, V, and p demonstrated OHR of 84% (Table 1). Melphalan (M) and dexamethasone (d): Sanchorawala et al. (n=70) reported patients treated with M and d showed OHR of 69%, with CR in 13% and PR in 25%. Similarly, a study by Lebovic et al. reported 40 pts who were given M, d. OHR was 58% and 13% pts showed CR (Table 1). High dose Melphalan/Stem Cell Transplant (HDM/SCT) with and without induction: In study by Cowan et al., (n=45) pts in group A (n=21) were given novel induction using agents like protease inhibitor (PI), cyclophosphamide, bortezomib and dexamethasone (CyBorD), Lenalidomide (L), dexamethasone (d) prior to high-dose melphalan (HDM). CR was observed in 50%, VGPR in 7% and PR in 7% pts. Group B (n=24) pts were given frontline HDM/SCT upfront. CR was observed in 28%, VGPR in 14% and PR in 14% pts. In a study by Scott et. al., 31 pts were categorized in 3 groups who received HDCT either with no induction, induction with V-based regimen and induction with other regimens including lenalidomide/dexamethasone (len/dex), melphalan/dexamethasone (mel/dex) and thalidomide/dexamethasone (Thal/dex). OHR in mel/dex cohort (n=3) was 67% (Table 1). In a study by Huang, X. et al., 56 pts were divided in two groups of 28 pts each. Pts in group A received Vd+HDM/SCT demonstrated CR in 67.9%, VGPR in 7.1%, PR in 10 .7 % and no response (NR) in 7.1 % pts. In group B, pts received with HDM/SCT upfront demonstrated CR in 35.7%, VGPR in 10.7%, PR in 2.1 % and no response NR in 21.4 % pts (Table 1). Randomized Standard dose Melphalan (SDM) versus HDM: In a study by Jaccard et al., there were two groups. The OHR was 68% in group A pts who were given SDM and high-dose dexamethasone (HD-dex) with CR in 31% and PR in 36% pts. The OHR was 67% in group B pts who were given HDM+ASCT with CR in 40% and PR in 25% pts (Table 1). Melphalan with Total body irradiaton (TBI): Vesole et al., reported 107 pts who were given M and TBI. OHR was 32% with CR in 16% and PR in 16% pts. mOS was 47.2 mo (Table 1). Melphalan (M), dexamethasone (d), Lenalidomide (L): In a clinical trial (NCT00890552) involving 25 pts M, d, and lenalidomide were give. CR, VGPR and PR were observed in 8%, 16% and 33%. 37.5% pts showed no-response (Table 1). Conclusion: Despite heterogeneity in the AL patient population and various regimens used in published literature, melphalan based regimens are very effective for treatment. Induction regimens and supportive care have evolved over the years. Novel combination regimens used for induction followed by HD-Melphalan consolidation along with careful selection of patients for high dose chemotherapy consolidation and stem cell transplantation in routine clinical practice is the best approach for personalized therapy selection for AL amyloidosis. Cytopenias of three cell lines are the major side effects reported with Mel therapy. Just like melphalan use for treatment of multiple myeloma in novel combination regimens, future randomized prospective trials are needed to better understand the efficacy and safety profile of melphalan based newer combination regimens for AL amyloidosis treatment. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.