A hallmark feature of tumorigenesis is uncontrolled cell division. Autophagy is regulated by more than 30 genes and it is one of several mechanisms by which cells maintain homeostasis. Autophagy promotes cancer progression and drug resistance. Several genes play important roles in autophagy‐induced tumorigenesis and drug resistance including Beclin‐1, MIF, HMGB1, p53, PTEN, p62, RAC3, SRC3, NF‐2, MEG3, LAPTM4B, mTOR, BRAF and c‐MYC. These genes alter cell growth, cellular microenvironment and cell division. Mechanisms involved in tumorigenesis and drug resistance include microdeletions, genetic mutations, loss of heterozygosity, hypermethylation, microsatellite instability and translational modifications at a molecular level. Disrupted or altered autophagy has been reported in hematological malignancies like lymphoma, leukemia and myeloma as well as multiple solid organ tumors like colorectal, hepatocellular, gall bladder, pancreatic, gastric and cholangiocarcinoma among many other malignancies. In addition, defects in autophagy also play a role in drug resistance in cancers like osteosarcoma, ovarian and lung carcinomas following treatment with drugs such as doxorubicin, paclitaxel, cisplatin, gemcitabine and etoposide. Therapeutic approaches that modulate autophagy are a novel future direction for cancer drug development that may help to prevent issues with disease progression and overcome drug resistance.

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.

Vaccination is an effective strategy to prevent infections in immunocompromised hematopoietic stem cell transplant recipients. Pretransplant vaccination of influenza, pneumococcus, Haemophilus influenza type b, diphtheria, tetanus, and hepatitis B, both in donors and transplant recipients, produces high antibody titers in patients compared with recipient vaccination only. Because transplant recipients are immunocompromised, live vaccines should be avoided with few exceptions. Transplant recipients should get inactive vaccinations when possible to prevent infection. This includes vaccination against influenza, pneumococcus, H. influenza type b, diphtheria, tetanus, pertussis, meningococcus, measles, mumps, rubella, polio, hepatitis A, human papillomavirus, and hepatitis B. Close contacts of transplant recipients can safely get vaccinations (inactive and few live vaccines) as per their need and schedule. Transplant recipients who wish to travel may need to get vaccinated against endemic diseases that are prevalent in such areas. There is paucity of data on the role of vaccinations for patients receiving novel immunotherapy such as bispecific antibodies and chimeric antigen receptor T cells despite data on prolonged B cell depletion and higher risk of opportunistic infections.

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Introduction: Major depressive disorder (MDD) often goes unrecognized in cancer patients. Some symptoms of major depression mimic signs and symptoms of malignancy due to which it often remains under-diagnosed. Depression has a contributing role in increasing the morbidity of cancer patients which if diagnosed and managed early in the treatment course can have a positive impact on cancer patients. This study focuses on determining the prevalence of major depression among cancer patients admitted in a tertiary care hospital in Lahore, Pakistan. Place & Duration: Mayo Hospital, Lahore. (March 01-30, 2019). Methods: After project approval and consent, a total of 187 patients were recruited in the study. Selection was made based on predefined criteria. Patients ranging between age group of 14-80 years in Mayo Hospital Lahore, Pakistan were included. Interviews were conducted through a pretested questionnaire based on DSM-5 (Diagnostic and Statistical Manual of Mental Disorders) criteria. Data was analyzed with Stata version 13. Patients were considered to be having major depressive disorder if they fulfill DSM-5 criteria for MDD; they must have 5 or more out of following 9 symptoms for ≥2 weeks: low mood, sleep disturbance (insomnia/hypersomnia), loss of interest in daily activities (anhedonia), feelings of guilt, low energy, loss of concentration, appetite changes (increased or decreased), psychomotor agitation/retardation and suicidal ideation. Symptoms should cause significant distress or impairment in social, occupational or other important areas of normal functioning and should not be attributable to the physiological effects of a substance (e.g., a drug of abuse, a medication) or another medical condition. The disturbance is not better explained by persistent psychiatric or psychotic disorders like schizophrenia, schizoaffective disorder, delusional disorder or other specified or unspecified schizophrenia spectrum and other psychotic disorders. Patients should not be currently on anti-depressants for any reason. Objectives: To determine the prevalence of major depression among cancer patients. Design: Cross-sectional study. Results: Out of 187 patients (171 in-patient, 16 outpatient), 116 (62%) were males and 71 (38%) were females with mean age of 44 years (SD±17.2). Descriptive analysis shows that 61 (33%) had hematological and 126 (67%) patients had non-hematological malignancies. 110 (59%) patients had low mood, 108 (57.7%) had insomnia, 77 (41%) lost interest in daily activities, 39 (21%) had feelings of guilt, 60 (32%) reported low energy, 13 (07%) were irritable, 120 (64%) noted decrease in appetite, 2 (1.0%) patients had suicidal ideation (not active). Seventy (37.4%) patients fulfilled the criteria to be clinically declared as suffering from major depression. Only 13 (7%) patients had prior knowledge of major depression. All variables showed positive correlation with MDD (ranging between +0.021 to +0.66) except hematological malignancies which were negatively correlated (-0.426). Regression analysis shows that patients having non-hematological malignancies were more likely to have MDD than hematological malignancies (Odds ratio [OR]: 25.07; 95% CI: 7.4-84.7; p<0.001). Stage 3 cancer patients had more odds to have MDD as compared to stage ≤2 (OR: 10.06; 95% CI: 1.17-85.7; p<0.01) and stage 4 cancer patients had even higher odds to be suffering from MDD in comparison to stage ≤2 (OR: 24.6; 95% CI: 2.8-214; p<0.01). Using PASS version 11; 95% CI, with 187 cancer patients, effect size of 0.502 with 1 df (degree of freedom), calculated power of this study is approximately 100%. The effect cells were calculated using cross table made between cancer classification and MDD (Table 2). Conclusion: Major depression is fairly prevalent but under recognized among cancer patients in Pakistani population. Patients having advanced non-hematological malignancies are more likely to have major depression as compared to other malignancy groups. Higher the cancer stage; higher the odds to have MDD. High clinical suspicion, appropriate questioning and psychiatry consultation should be routinely asked if there is high suspicion. Only few patients had the prior knowledge about depression so patients need to be screened and counseled regarding their symptoms and treatment should be tailored accordingly. Disclosures Anwer: In-Cyte: Speakers Bureau; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees.