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• XmAb5574 is an Fc-engineered CD19 monoclonal antibody that is well tolerated as a single agent in patients with relapsed or refractory CLL.• XmAb5574 has preliminary efficacy as a single agent in CLL and is of interest for further study in this disease.CD19 is ubiquitously expressed on chronic lymphocytic leukemia (CLL) cells and is therefore an attractive candidate for antibody targeting. XmAb5574 (aka MOR00208) is a novel humanized CD19 monoclonal antibody with an engineered Fc region to enhance Fcg receptor binding affinity. Here we report results of a first in human phase 1 trial of XmAb5574 in patients with relapsed or refractory CLL. Twenty-seven patients were enrolled to 6 escalating dose levels, with expansion at the highest dose level of 12 mg/kg. Nine doses of XmAb5574 were infused over 8 weeks. No maximal tolerated dose was reached, and the drug was generally well tolerated, with infusion reactions of grades 1 and 2 being the most common toxicities. Grade 3 and 4 toxicities occurred in 5 patients and included neutropenia, thrombocytopenia, increased aspartate aminotransferase, febrile neutropenia, and tumor lysis syndrome. XmAb5574 showed preliminary efficacy, with 18 patients (66.7%) responding by physical examination criteria and laboratory studies, and 8 patients (29.6%) responding by computed tomography criteria. Pharmacokinetics showed a half-life of 14 days with clearance that was not dose-dependent. In conclusion, this phase 1 trial demonstrates safety and preliminary efficacy of a novel Fc-engineered CD19 monoclonal antibody XmAb5574 and justifies movement into the phase 2 setting. This trial was registered at www.clinicaltrials.gov as #NCT01161511. (Blood. 2014;124(24):3553-3560)

ContextOver one year after passage of the Patient Protection and Affordable Care Act (PPACA), legislators, healthcare experts, physicians, and the general public continue to debate the implications of the law and its repeal. The PPACA will have a significant impact on future physicians, yet medical student perspectives on the legislation have not been well documented.ObjectiveTo evaluate medical students' understanding of and attitudes toward healthcare reform and the PPACA including issues of quality, access and cost.Design, Setting, and ParticipantsAn anonymous electronic survey was sent to medical students at 10 medical schools (total of 6982 students) between October–December 2010, with 1232 students responding and a response rate of 18%.Main Outcome MeasuresMedical students' views and attitudes regarding the PPACA and related topics, measured with Likert scale and open response items.ResultsOf medical students surveyed, 94.8% agreed that the existing United States healthcare system needs to be reformed, 31.4% believed the PPACA will improve healthcare quality, while 20.9% disagreed and almost half (47.7%) were unsure if quality will be improved. Two thirds (67.6%) believed that the PPACA will increase access, 6.5% disagreed and the remaining 25.9% were unsure. With regard to containing healthcare costs, 45.4% of participants indicated that they are unsure if the provisions of the PPACA will do so. Overall, 80.1% of respondents indicated that they support the PPACA, and 78.3% also indicated that they did not feel that reform efforts had gone far enough. A majority of respondents (58.8%) opposed repeal of the PPACA, while 15.0% supported repeal, and 26.1% were undecided.ConclusionThe overwhelming majority of medical students recognized healthcare reform is needed and expressed support for the PPACA but echoed concerns about whether it will address issues of quality or cost containment.

BackgroundAdvocacy is increasingly being recognized as a core element of medical professionalism and efforts are underway to incorporate advocacy training into graduate and undergraduate medical school curricula. While limited data exist to quantify physician attitudes toward advocacy, even less has been done to assess the knowledge, skills, and attitudes of future physicians. The purpose of this study was to assess students’ experiences and attitudes toward legislative advocacy, cutting out using a convience sample.MethodsA paper survey based on previously validated surveys was administered to a convenience sample of premedical and medical student participants attending a National Advocacy Day in Washington, DC, in March 2011, both before and after their advocacy experiences. Responses were anonymous and either categorical ( or ordinal, using a 5-point Likert scale. Data were analyzed statistically to evaluate demographics and compare changes in pre- and post-experience attitude and skills.ResultsData from 108 pre-advocacy and 50 post-advocacy surveys were analyzed yielding a response rate of 46.3%. Following a single advocacy experience, subjects felt they were more likely to contact their legislators about healthcare issues (p = 0.03), to meet in person with their legislators (p < 0.01), and to advocate for populations' health needs (p = 0.04). Participants endorsed an increased perception of the role of a physician advocate extending beyond individual patients (p = 0.03). Participants disagreed with the statement that their formal curricula adequately covered legislative healthcare advocacy. Additionally, respondents indicated that they plan to engage in legislative advocacy activities in the future (p < 0.01).ConclusionsA one-time practical advocacy experience has a positive influence on students’ knowledge, skills and attitudes towards legislative advocacy. Practical experience is an important method of furthering medical education in advocacy and further research is necessary to assess its impact in a broader population.