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Light chain multiple myeloma (LCMM) constitutes approximately 15% of patients with multiple myeloma (MM). It has a poorer prognosis when compared to immunoglobulin (Ig) G or IgA variant. We performed a comprehensive literature search on LCMM and identified a total of 390 articles. After a detailed screening, six studies involving a total of 1054 LCMM patients were included. A literature review revealed bone pain and renal failure as the most common initial sign and symptoms while extramedullary disease (EMD) was acquired later during the progression of the disease. Bortezomib has shown superior efficacy in LCMM patients over nonbortezomib regimens as demonstrated by better overall response rate (95.5% vs. 60%), progression-free survival (PFS) (25% vs. 9% at two years), and overall survival (OS) (24% vs. 9% at five years). Moreover, better PFS was seen, when bortezomib was used in combination with bendamustine compared to dexamethasone (95% vs. 25% at two years). Similarly, better OS (90% at two years) was observed with bortezomib in combination with bendamustine. Monitoring of disease should include serum free light chain levels, as literature review revealed that serum assays were more sensitive in indicating the disease and predicting PFS and OS as compared to urine assays. We provide presentation patterns, clinical rarities, management strategies including their efficacy, and disease monitoring in patients with LCMM in our review paper.

Immunoglobulin (Ig) D multiple myeloma (MM) is a rare subtype of MM comprising 2% of all the cases. Malignant plasma cell invasion leads to signs and symptoms similar to other subtypes of MM. The synthesis rate of IgD is lower in IgD MM patients, making it very difficult to diagnose compared to other subtypes. As there is no available diagnostic test with 100% accuracy, the diagnosis of IgD MM is based on multiple factors. Recent advances in the treatment have resulted in a better overall survival for IgD MM patients. The aim of this systematic review was to summarize the data on presentation patterns, diagnosis modalities, management strategies, and outcomes in patients with IgD MM.

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.

Enteric fever is a common infectious disease, especially in countries with poor sanitation and in the tropics. It is caused mainly by Salmonella typhi and accounts for nearly 27 million cases worldwide and 200,000 deaths annually. Enteric fever involves the reticuloendothelial system such as bone marrow, spleen, and liver. As it mostly involves the Peyer’s patches of the terminal ileum, enteric perforation occurs commonly. However, gallbladder perforation can also occur, though not very often. Ultrasound as well as computerized tomography (CT) abdomen and pelvis lack specificity for detecting gallbladder perforations in enteric fever. Diagnosis is usually confirmed intraoperatively when the gallbladder is visualized and perforation is seen. Gallbladder perforation is usually seen in acute cholecystitis when the gallbladder becomes necrotic and gangrenous. In acalculous cholecystitis, perforation is rare. Enteric fever is one of the rarest causes of acalculous cholecystitis, leading to perforation. Here, we present the case of a 20-year-old man who presented with fever for 10 days along with loose stools, vomiting, and acute abdomen. Labs showed leukopenia, positive Typhidot test but X-ray erect abdomen and ultrasound abdomen and pelvis were nonspecific. Only after resuscitation and exploration of the abdomen was it found that the gallbladder had multiple perforations. The patient was improved after eight days of postoperative intravenous antibiotics. This is a unique and rare presentation of such a common infectious disease.