Selinexor for the treatment of patients with relapsed or refractory multiple myeloma.

OBJECTIVE: Multiple myeloma cells resist standard therapies due to overexpression of the transport protein, exportin 1. Selinexor is a novel drug that targets the Exportin 1 protein in these cells. DATA SOURCE: A comprehensive search was done, and data showing the efficacy and safety of selinexor in relapsed/refractory multiple myeloma was collected using PubMed, Google Scholar, and clincialtrials.gov. DATA SUMMARY: Results from the clinical trials STORM, BOSTON, and STOMP were included. Parts I and II of the STORM trial revealed a progression-free survival (PFS) of 4.7 and 3.7 months, a median duration of response of 6.2 and 4.4 months, and an overall survival of 7.3 and 8.4 months, respectively. BOSTON trial's SVd arm (selinexor, bortezomib, and dexamethasone) had a median follow-up period of 13.2 months and an mPFS of 13.93 months. The Vd arm (bortezomib and dexamethasone) had a median follow-up duration of 16.5 months and an mPFS of 9.46 months. The STOMP trial is still active and has limited data available. The SKd arm (selinexor, carfilzomib, and dexamethasone) reported an overall response rate of 66.7% in patients with triple refractory multiple myeloma, and 82% in patients with high-risk cytogenetics. The SPd arm (selinexor, pomalidomide, and dexamethasone) shows an overall response rate of 54.30% in pomalidomide naïve-nonrefractory, 35.70% in pomalidomide refractory and 60% in those dosed at RP2D. SRd arm (selinexor, lenalidomide, and dexamethasone) shows an overall response rate of 91.7% in lenalidomide naïve and 12.5% in lenalidomide refractory patients. SVd (selinexor, bortezomib, and dexamethasone) arm reported an overall response rate of 63% in all patients while the SDd arm (selinexor, daratumumab, and dexamethasone) showed an overall response rate of 73%. CONCLUSION: To improve the outcome of patients with relapsed/refractory multiple myeloma, it is critical to develop new therapies, assess potential therapeutic synergies, and overcome drug resistance by determining the efficacy of multiple myeloma therapies across multiple disease subgroups.

Spectrum of Papillary Breast Lesions According to World Health Organization Classification of Papillary Neoplasms of Breast.

Introduction Papillary breast lesions are segregated into benign and malignant based on the presence or absence of myoepithelial cells in the papillary cores. Papillary breast lesions are further classified into: intraductal papilloma, papilloma with atypical ductal hyperplasia (ADH)/ductal carcinoma in situ (DCIS), papillary DCIS, solid papillary carcinoma in situ, solid papillary carcinoma with invasion, invasive solid papillary carcinoma, encapsulated papillary carcinoma and encapsulated papillary carcinoma with invasion. In this study, we evaluated the spectrum of papillary breast lesions in resection specimens of the breast according to the latest World Health Organization (WHO) classification of breast tumors. Methods This was a retrospective cross-sectional study, and was conducted at Liaquat National Hospital for a period of six years, from January 2012 till December 2017. Data of patients that underwent surgeries for breast tumors were included in the study. All specimens were grossed, according to defined protocols, and representative sections were taken after inking resection margins. Hematoxylin and eosin-stained sections were examined by experienced histopathologists, and myoepithelial stains (p63 and myosin) were done in selected sections of all tumors. Histopathological classification of papillary tumors was performed according to WHO classification of breast tumors. Results The study involved 190 excision specimens of papillary breast lesions. Mean age of the patients was 45.6±17.1 years. Most of the lesions were between two and five centimetres (69.1%). For invasive carcinomas (n = 76), the most frequent grade was II (52.6%). For in situ and invasive carcinomas (n = 129), lymphovascular invasion and axillary metastasis were noted in 5.4% and 9.3% cases, respectively. Among papillary breast lesions, 36.8% were benign (intraductal papilloma, solitary or multiple) while 63.2% harbored ADH, DCIS, or invasive carcinoma. Invasive papillary carcinoma was the most frequent malignant papillary lesion (20%), followed by solid papillary carcinoma with invasion (12.6%). We found significant associations between patient's age and tumor size with histological type of papillary lesion as benign papillary lesions had smaller size and younger age compared to malignant papillary lesions. Conclusion We noted a high frequency of malignancy in papillary breast lesions. Moreover, malignant papillary lesions were significantly associated with higher age and larger tumor size.

Prognostic Implications of Deep Muscle Invasion and High Grade for Bladder Urothelial Carcinoma.

Introduction Urothelial carcinoma (UC) is the most common bladder cancer. The most censorious pathological aspect of UC is deep muscle invasion and tumor grade. In this study, we assessed the prognostic implications of tumor grade and deep muscle invasion in UC. Methods It was a retrospective cross-sectional study conducted at the Department of Histopathology, Liaquat National Hospital, from July to December 2019. The data were collected over five years from January 2014 till December 2018. Records from archives of the anatomic pathology were searched, clinical characteristics were recorded, and histopathological slides were reviewed. Histological parameters, including tumor grade and muscle invasion, were evaluated. Records of patient follow-up were assessed by reviewing clinical records. Recurrence of UC and overall survival was also recorded. Multivariate binary logistic regression was applied for variables that were significant on univariate logistic regression. Survival analysis was performed using the Kaplan-Meier method. Results The mean age of the patients was 63.39 ± 14.1 years. More than half (53%) cases were of low-grade papillary UC. Disease recurrence was observed in 53 (39.1%) patients, whereas the mortality rate was 16.6%. In our study, 49 (32.5%) patients were found to have deep muscle invasion. By multivariate analysis, we found that the deep muscle invasion was significantly associated with male gender and grade. In addition, a significant association of high-tumor grade with survival status of the patients was noted. Conclusions A high proportion of UC cases in our study were found to have deep muscle invasion and high-tumor grade. Moreover, a significant association of deep muscle invasion with tumor grade and an association of tumor grade with survival signify the prognostic value of these factors in UC.