CAR T-cell therapy: is it prime time in myeloma?

Chimeric antigen receptor (CAR) T cells have shown promising activity in hematological malignancies and are being studied for the treatment of multiple myeloma, as well. B-cell maturation antigen, which is widely and almost exclusively expressed on plasma cells and B cells, is a promising target. Other targets being evaluated include CD19, CD38, CD138, signaling lymphocyte activation molecule or CS1, light chain, GPRC5D, and NKG2D. Early clinical studies have shown promising response rates in heavily pretreated patients, but relapses have occurred. Cytokine release syndrome and neurotoxicity have been observed in the majority of patients but are mostly grades 1 and 2. Relapse may be mediated by antigen escape and the limited persistence of CAR T cells. CAR T-cell constructs that target multiple antigens/epitopes or constructs with longer persistence due to a higher proportion of memory phenotype T cells may decrease the rates of relapse. Allogeneic CAR T cells that offer "off-the-shelf" options are also being developed. The challenges in integrating CAR T cells in myeloma therapy include disease relapse, adverse effects, cost, and identifying the right patient population. Longer-term data on efficacy and toxicity are needed before CAR T cells are ready for prime time in myeloma

CAR T-cell therapy: is it prime time in myeloma?

Chimeric antigen receptor (CAR) T cells have shown promising activity in hematological malignancies and are being studied for the treatment of multiple myeloma, as well. B-cell maturation antigen, which is widely and almost exclusively expressed on plasma cells and B cells, is a promising target. Other targets being evaluated include CD19, CD38, CD138, signaling lymphocyte activation molecule or CS1, light chain, GPRC5D, and NKG2D. Early clinical studies have shown promising response rates in heavily pretreated patients, but relapses have occurred. Cytokine release syndrome and neurotoxicity have been observed in the majority of patients but are mostly grades 1 and 2. Relapse may be mediated by antigen escape and the limited persistence of CAR T cells. CAR T-cell constructs that target multiple antigens/epitopes or constructs with longer persistence due to a higher proportion of memory phenotype T cells may decrease the rates of relapse. Allogeneic CAR T cells that offer "off-the-shelf" options are also being developed. The challenges in integrating CAR T cells in myeloma therapy include disease relapse, adverse effects, cost, and identifying the right patient population. Longer-term data on efficacy and toxicity are needed before CAR T cells are ready for prime time in myeloma

Depression and Medical Students in New Delhi

Background Medical education is associated with various pressures and stresses which can lead to depression. This study was undertaken to discover the prevalence of depression in medical students and various factors contributing to depression. Method This is a cross-sectional, questionnaire-based study. Using stratified random sampling, 237 students were selected according to year of study. Patient Health Questionnaire (PHQ-9), based on PRIME-MD Today, was used to make a provisional diagnosis of depression. Results and conclusions The overall prevalence of provisionally diagnosed depressive and major depressive disorder using PHQ-9 was 21.5% and 7.6%, respectively. Year of study and academic performance of students had a statistically significant association with depression. Other factors, including gender, self-reported past history of depression, family history of psychiatric disorders, type of social support, family structure, number of siblings and education of parents were not found to have any significant association with prevalence of depression in the study. It was also observed that students were reluctant to seek help for depressive symptom

Symptomatic and incidental venous thromboembolic disease are both associated with mortality in patients with prostate cancer.

The association between malignancy and venous thromboembolic disease (VTE) is well established. The independent impact of VTE, both symptomatic and incidental, on survival in patients with prostate cancer is not known. We conducted a retrospective cohort study to evaluate the effect of VTE of survival in prostate cancer.Data regarding clinical characteristics, treatment and outcomes of 453 consecutive prostate cancer patients were collected. Fisher exact (categorical variables) and t-test (continuous variables) were utilized to test associations with VTE and mortality. Survival was estimated using the Kaplan Meier method. A Cox regression model was used to model the mortality hazard ratio (HR).At diagnosis, 358 (83%) patients had early stage disease, 43 (10%) had locally advanced disease and 32 (7%) had metastatic disease. During the follow up period, 122 (27%) patients died and 41 (9%) developed VTE (33 deep vein thrombosis, 5 pulmonary embolism, and 3 patients with both DVT and PE). Twenty-five VTE events were symptomatic and 16 were incidentally diagnosed on CT scans obtained for other reasons. VTE was associated with increased mortality [HR 6.89 (4.29-11.08), p<0.001] in a multivariable analysis adjusted for cancer stage, performance status, treatments and co-morbidities. There was no difference in survival between patients who had symptomatic and incidental VTE.Venous thromboembolic disease, both symptomatic and incidental, is a predictor of poor survival in patients with prostate cancer, especially those with advanced disease. Further studies are needed to evaluate the benefit of prophylactic and therapeutic anticoagulation in this population

Kaplan Meier curve showing survival of patients who developed VTE with date of VTE as time origin.

<p>Thirty-five of 41 (85.3%) patients with VTE died, 20 (57.1%) within 1 year.</p

Characteristics of patients with VTE.

<p>* Five (20%) of 25 symptomatic patients were diagnosed with pulmonary emboli (PE) and 20 (80%) were diagnosed with deep vein thrombosis (DVT) alone while 3 (18.7%) of patients with incidental VTE were diagnosed with PE and 13 (81.3%) with DVT.</p