Background Although complement component 5 inhibitors (C5is) eculizumab and ravulizumab improve paroxysmal nocturnal hemoglobinuria (PNH) outcomes, patients may experience persistent anemia. This ...post hoc analysis investigated whether the complement component 3-targeted therapy pegcetacoplan also improved hematologic outcomes and reduced fatigue in patients with PNH and mild/moderate anemia. Methods Patients with PNH and hemoglobin ≥10.0 g/dL at baseline of PADDOCK (N = 6), PRINCE (N = 8), and PEGASUS (N = 11) were included. Before receiving pegcetacoplan, PADDOCK and PRINCE patients were C5i-naive; PEGASUS patients had hemoglobin <10.5 g/dL despite stably dosed eculizumab. Hemoglobin concentrations, percentages of patients with concentrations ≥12 g/dL, and sex-specific normalization were assessed at baseline and after 16 weeks of pegcetacoplan, as were absolute reticulocyte counts (ARCs) and normalization and fatigue scores and normalization. Results From baseline to week 16, mean (SD) hemoglobin concentrations increased in C5i-naive patients (PADDOCK: 10.5 0.4 to 12.7 1.1 g/dL; PRINCE: 11.3 1.0 to 14.0 1.3 g/dL) and those with suboptimal eculizumab responses (PEGASUS: 10.2 0.2 to 12.8 2.6 g/dL). Percentage of patients with hemoglobin ≥12 g/dL increased (PADDOCK: 0 to 60.0% 3 of 5 patients; PRINCE: 25.0% 2 of 8 to 87.5% 7 of 8; PEGASUS: 0 to 72.7% 8 of 11). Sex-specific hemoglobin normalization at week 16 occurred in 40.0% (2 of 5) (PADDOCK), 62.5% (5 of 8) (PRINCE), and 63.6% (7 of 11) (PEGASUS). In all studies, mean ARCs decreased from above normal to normal and ARC normalization increased. Mean Functional Assessment of Chronic Illness Therapy–Fatigue scores improved from below to above or near normal. Two patients had serious adverse events (PEGASUS: post-surgery sepsis, breakthrough hemolysis); breakthrough hemolysis resolved without study discontinuation. Conclusion Patients with PNH and mild/moderate anemia who were C5i-naive or who had suboptimal hemoglobin concentrations despite eculizumab treatment had improved hematologic outcomes and reduced fatigue after initiating or switching to pegcetacoplan. Trial registration Trial registration numbers: PADDOCK ( NCT02588833 ), PRINCE ( NCT04085601 ; EudraCT, 2018-004220-11), PEGASUS ( NCT03500549 ).
Abstract Objective To develop a feasibility study of a theory-driven telephone counseling program to enhance psychosocial and physical well-being for cancer survivors after treatment. Methods ...Participants ( n = 66) were recruited from two Colorado hospitals with self-administered questionnaires at baseline and two weeks post-intervention. The one group, intervention only design included up to six thematic telephone counseling sessions over three months. Topics included nutrition, physical activity, stress management, and medical follow-up. Primary outcomes were cancer-specific distress, self-reported fruit and vegetable consumption and physical activity. Results Of 66 subjects, 46 completed at least one counseling module and the follow-up assessment (70% retention rate). Mean satisfaction was 9 out of 10, and all participants would recommend C-STEPS to other survivors. Cancer-specific distress (Impact of Event Scale – Intrusion subscale) decreased for entire study population ( p < 0.001) and stress management session participants ( p < 0.001). Fruit and vegetable consumption increased for nutrition and exercise session participants ( p = 0.02) and the entire sample ( p = NS). Physical activity increased in the entire group ( p = 0.006) and for nutrition and exercise session participants ( p = 0.01). Conclusion and practice implications C-STEPS is a feasible telephone counseling program that transcends geographic barriers, demonstrating the potential to decrease distress and promote coping and healthy lifestyles among cancer survivors.
Ensuring equitable access to health care is a widely agreed-upon goal in medicine, yet access to care is a multidimensional concept that is difficult to measure. Although frameworks exist to evaluate ...access to care generally, the concept of "access to genomic medicine" is largely unexplored and a clear framework for studying and addressing major dimensions is lacking.
Comprised of seven clinical genomic research projects, the Clinical Sequencing Evidence-Generating Research consortium (CSER) presented opportunities to examine access to genomic medicine across diverse contexts. CSER emphasized engaging historically underrepresented and/or underserved populations. We used descriptive analysis of CSER participant survey data and qualitative case studies to explore anticipated and encountered access barriers and interventions to address them.
CSER's enrolled population was largely lower income and racially and ethnically diverse, with many Spanish-preferring individuals. In surveys, less than a fifth (18.7%) of participants reported experiencing barriers to care. However, CSER project case studies revealed a more nuanced picture that highlighted the blurred boundary between access to genomic research and clinical care. Drawing on insights from CSER, we build on an existing framework to characterize the concept and dimensions of access to genomic medicine along with associated measures and improvement strategies.
Our findings support adopting a broad conceptualization of access to care encompassing multiple dimensions, using mixed methods to study access issues, and investing in innovative improvement strategies. This conceptualization may inform clinical translation of other cutting-edge technologies and contribute to the promotion of equitable, effective, and efficient access to genomic medicine.
Eculizumab is a novel monoclonal antibody that inhibits complement-mediated hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH). Complement deficiency is a well-known risk factor for ...meningococcal infection. We describe a case of a young patient with PNH treated with eculizumab who presented with a life-threatening case of nongroupable meningococcemia. As this new biologic agent becomes more widely prescribed, providers should be aware of the increased risk of meningococcemia. In addition to vaccination, providers may consider the use of oral penicillin for antibiotic prophylaxis against Neisseria meningitidis in these cases of functional complement deficiency.
Although complement component 5 inhibitors (C5is) eculizumab and ravulizumab improve paroxysmal nocturnal hemoglobinuria (PNH) outcomes, patients may experience persistent anemia. This post hoc ...analysis investigated whether the complement component 3-targeted therapy pegcetacoplan also improved hematologic outcomes and reduced fatigue in patients with PNH and mild/moderate anemia. From baseline to week 16, mean (SD) hemoglobin concentrations increased in C5i-naive patients (PADDOCK: 10.5 0.4 to 12.7 1.1 g/dL; PRINCE: 11.3 1.0 to 14.0 1.3 g/dL) and those with suboptimal eculizumab responses (PEGASUS: 10.2 0.2 to 12.8 2.6 g/dL). Percentage of patients with hemoglobin greater than or equal to12 g/dL increased (PADDOCK: 0 to 60.0% 3 of 5 patients; PRINCE: 25.0% 2 of 8 to 87.5% 7 of 8; PEGASUS: 0 to 72.7% 8 of 11). Sex-specific hemoglobin normalization at week 16 occurred in 40.0% (2 of 5) (PADDOCK), 62.5% (5 of 8) (PRINCE), and 63.6% (7 of 11) (PEGASUS). In all studies, mean ARCs decreased from above normal to normal and ARC normalization increased. Mean Functional Assessment of Chronic Illness Therapy-Fatigue scores improved from below to above or near normal. Two patients had serious adverse events (PEGASUS: post-surgery sepsis, breakthrough hemolysis); breakthrough hemolysis resolved without study discontinuation. Trial registration
Stage III melanoma, also referred to as regional metastatic melanoma, has five-year survival rates ranging between 40% and 78%. In order to reduce the likelihood of recurrence in this high-risk ...population, patients undergo resection of primary tumors and all involved nodal basins. Systemic therapy is being pursued in an effort to improve outcome data, but the best strategy has yet to be defined. Interferon alpha-2b remains to date the most promising approach available. Toxicities and intensive intravenous administration, unfortunately, are major concerns. An alternative is the use of interferon in its pegylated subcutaneous form. The aim of this research was to review the evidence for the use of pegylated interferon alpha-2b in Stage III malignant melanoma.
ECOG 1684 was the pivotal trial that first demonstrated a statistically significant benefit in relapse-free and overall survival for adjuvant interferon alpha-2b in high-risk melanoma. Other larger studies, such as ECOG 1690, confirmed a relapse-free survival benefit but did not achieve statistical significance for overall survival. The first study of the pegylated form of interferon alpha-2b in Stage III melanoma, EORTC 18991, is reviewed here. This trial showed a statistically significant improvement in relapse-free survival but not overall survival. Encouraging data of potential equivalent efficacy, easier administration, and fewer Grade 3 and 4 adverse reactions compared with high-dose intravenous interferon raises the question of its potential role in Stage III melanoma in the adjuvant setting.
We present and describe tailored strategies to address known barriers to minority participation in clinical trial research. The strategies used allowed our team to engage communities and successfully ...recruit, enroll, and retain a diverse underserved population of Latinos with advanced cancer for this clinical trial.
Participants were recruited from 3 urban and 7 rural sites. We identified 4 critical barriers to recruitment for this underserved population: (1) mistrust; (2) language and communication barriers; (3) lack of access to academic cancer center; and (4) inability to participate due to transportation, childcare, or work responsibilities. We developed tailored strategies to engage referring sites and patients to participate in the clinical trial.
We identified 318 potentially eligible participants; 34 were found to be ineligible, and 223 consented to participate in the study, representing a 79.0% enrollment rate. All patients (100%) self-identified as Latino, and 47.5% spoke Spanish as their primary language. Patients were socioeconomically disadvantaged: 53.6% had an annual income <$15,000 USD, and 50.2% had less than a high school education. A total of 177 participants completed the 3-month follow-up; 26 died before the 3-month follow interview, and 20 did not complete the follow-up evaluation (9% withdrawal rate).
Our community-informed strategies were highly effective for recruiting, enrolling, and retaining an underserved diverse population of Latinos. The barriers we identified and the strategies we used have the potential to inform research to increase minority participation in cancer clinical trials. ClinicalTrials.gov identifier: NCT01695382.
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