Citations 82
Survival trends among non‐small‐cell lung cancer patients over a decade: impact of initial therapy at academic centers
Lou, Yanyan , Dholaria, Bhagirathbhai , Soyano, Aixa , Hodge, David O. , Cochuyt, Jordan J., Thomas, Mathew , Johnson, Margaret M. , Patel, Neal M. , Miller, Robert C. , Adjei, Alex A. , Hodge, David, Cochuyt, Jordan, Manochakian, Rami , Ko, Stephen J. , Ailawadhi, Sikander , Thomas, Mathew , Dholaria, Bhagirathbhai R , Soyano, Aixa , Ailawadhi, Sikander
Cancer Medicine | September 2, 2018 | Volume: 7 | Issue: 10 | Pages: 4932-4942
Abstract Background Treatment of non‐small‐cell lung cancer (NSCLC) has been rapidly advancing over the last decade. Academic centers are considered equipped with better expertise. NSCLC outcome trends in novel therapeutic era and impact of initial treatment at academic centers have not been reported. Methods The National Cancer Database (NCDB) was used to identify NSCLC incident cases from 2004 to 2013. Overall survival (OS) was plotted by year of diagnosis and type of initial treatment center, accounting for several factors available in NCDB. Results A total of 1 150 722 NSCLC patients were included and separated by initial treatment center type (academic: 31.5%; nonacademic: 68.5%). Median follow‐up and OS for all patients were 11.8 months (range: 0‐133.6 months) and 13.1 months (95% CI: 13.08‐13.17), respectively. Median OS improved significantly for those diagnosed in 2010‐2013 (14.8 months [95% CI: 14.7‐14.9]) as compared to 2004‐2009 (12.4 months [95% CI: 12.3‐12.5]) ( P < 0.001). Treatment at academic centers was associated with improved OS (multivariate HR for OS = 0.929 [95% CI: 0.92‐0.94], P < 0.0010). Four‐year OS for academic and nonacademic cohorts was 28.5%% and 22.1%, respectively ( P < 0.001), and the difference was more pronounced in stage I to III NSCLC. Conclusion In this largest analysis, thus far, NSCLC survival has improved over time, and type of initial treatment center significantly influences survival. Identifying and removing barriers to obtaining initial treatment of NSCLC at academic medical centers could improve OS.
Targeting CD38 with daratumumab is lethal to Waldenström macroglobulinaemia cells
Paulus, Aneel , Manna, Alak , Akhtar, Sharoon , Paulus, Shumail M., Sharma, Mayank , Coignet, Marie V. , Jiang, Liuyan , Ansell, Stephen M. , Allan, John N. , Furman, Richard R. , Aulakh, Sonikpreet , Chanan‐Khan, Asher , Sher, Taimur , Manochakian, Rami , Ailawadhi, Sikander , Chanan-Khan, Asher A., Paulus, Aneel , Roy, Vivek , Witzig, Thomas E. , Ailawadhi, Sikander
British Journal of Haematology | August 7, 2018 | Volume: 183 | Issue: 2 | Pages: 196-211
SummaryCD38 is expressed on Waldenström macroglobulinaemia (WM) cells, but its role as a therapeutic target remains undefined. With recent approval of the anti‐CD38 monoclonal antibody, daratumumab (Dara), we hypothesized that blocking CD38 would be lethal to WM cells.In vitroDara treatment of WM cells (including ibrutinib‐resistant lines) elicited antibody‐dependent cellular cytotoxicity (ADCC), complement‐dependent cytotoxicity (CDC), antibody‐dependent cell phagocytosis (ADCP) and direct apoptosis.In vivo, Dara treatment was well tolerated and delayed tumour growth in RPCI‐WM1‐xenografted mice. CD38 is reported to augment B‐cell receptor (BCR) signalling; we noted that Dara significantly attenuated phosphorylated SYK, LYN, BTK, PLCγ2, ERK1/2, AKT, mTOR, and S6 levels, and this effect was augmented by cotreatment with ibrutinib. Indeed, WM cells, including ibrutinib‐resistant WM cell lines treated with the ibrutinib + Dara combination, showed significantly more cell death through ADCC, CDC, ADCP and apoptosis relative to single‐agent Dara or ibrutinib. In summary, we are the first to report thein vitroandin vivoanti‐WM activity of Dara. Furthermore, we show a close connection between BCR and CD38 signalling, which can be co‐targeted with ibrutinib + Dara to induce marked WM cell death, irrespective of acquired resistance to ibrutinib.