Patient-reported experiences during and following treatment with belantamab mafodotin for relapsed/refractory multiple myeloma in the DREAMM-2 study.

Introduction: Patients with relapsed or refractory multiple myeloma (RRMM) are likely to be living with persistent symptoms, especially bone pain and fatigue, and experiencing restrictions in their physical and social functioning, which reduce health-related quality of life. Methods: This qualitative interview study evaluated patients' perspectives about living with RRMM and their treatment with belantamab mafodotin, using interviews embedded in the Phase II DREAMM-2 trial (NCT03525678) with belantamab mafodotin. Patients consented to participate in up to 2 recorded telephone interviews (at treatment cycle 4 [C4] and at end of treatment [EOT]) comprising open-ended questions. Results: A total of 142 interviews were conducted with 111 unique patients. At C4, common symptoms included neuropathy, fatigue, and bone or joint pain. Improvements in symptom severity were reported by patients who responded to belantamab mafodotin. Symptoms associated with visual impairment, eye irritation, and eye pain reported during the trial were reported to be at- or near-resolution by the EOT interview. Regarding impacts of underlying MM, patients most commonly expressed concerns about changes in daily performance and lifestyle for both responders (67.5% of all impact expressions) and non-responders (63.2%). Overall, interview participants reported being satisfied with belantamab mafodotin treatment. Discussion: This qualitative patient interview study provides valuable insight into patients' symptomatic experience with belantamab mafodotin for their RRMM treatment and may help healthcare providers better anticipate their patients' real-world experience and needs when prescribing this novel agent in the clinic.

Perspectives of patients with advanced or metastatic non-small cell lung cancer on symptoms, impacts on daily activities, and thresholds for meaningful change: a qualitative research study.

Introduction: Advanced or metastatic non-small cell lung cancer (NSCLC) is associated with significant symptom burden. It is important to understand the impact of these disease-and treatment-related symptoms on patients' daily lives and explore from a patient perspective what constitutes a meaningful change in NSCLC symptoms. Methods: Patient experience of advanced or metastatic NSCLC was explored in this prospective, non-interventional qualitative research study recruiting patients from the United States (US). Interviews were conducted to explore the most important symptoms, daily life impacts, and patients' perspectives of what constitutes meaningful change when considering their current symptoms versus 6-12 months prior, based on the Patient Global Impression of Severity (PGI-S) and Patient Global Impression of Change (PGI-C) items. Results: Between February and April 2022, 19 US-based patients with Stage IV NSCLC were recruited; 95% were female, 63% were White, 79% had been diagnosed >1 year prior, and 63% were receiving targeted therapy. Over half the patients indicated their most important symptoms were fatigue, shortness of breath, and cough. Patient differentiation between whether symptoms were disease- or treatment-related lacked concordance, and often patients were unable to distinguish the two. The most frequently mentioned impacts of these symptoms on patients' daily lives were difficulty walking, sleep disturbance, anxiety/depression, impact on relationships, and difficulty doing daily tasks. Most patients considered a one-point change on the PGI-S or PGI-C to be meaningful based on rating their symptom severity at the time of the interview compared with 6-12 months before the interview. Conclusion: Based on their own symptom experience, patients with advanced or metastatic NSCLC indicated a one-point threshold for meaningful change, whether improvement or worsening. This suggests a one-point change on the PGI-S or PGI-C may be a potential anchor for patient-reported outcome (PRO) endpoints used in clinical trials. It is important to use PRO instruments that capture the symptoms and impacts identified as most important to patients. These findings highlight the importance of using qualitative methods to assess disease-related symptoms, treatment-related side effects, and the impacts on daily life for patients with advanced or metastatic NSCLC, underscoring how qualitative assessments can complement quantitative PRO instruments for evaluating clinical trials.

A toolbox of different approaches to analyze and present PRO-CTCAE data in oncology studies.

BACKGROUND: The patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is used to assess symptomatic adverse events in oncology trials. Currently, no standard for PRO-CTCAE analysis exists. METHODS: Key methods of descriptive analysis and longitudinal modeling using PRO-CTCAE data from an oncology clinical trial, DRiving Excellence in Approaches to Multiple Myeloma-2 (DREAMM-2), a phase II trial of belantamab mafodotin in multiple myeloma (NCT03525678), were explored. Descriptive methods included maximum postbaseline ratings, mean change over time, ratings above a predefined cutoff, line graphs, and stacked bar charts to illustrate patient-reported adverse events at one timepoint or dynamics over time. Analysis methods involving modeling over time included toxicity over time (ToxT) (repeated measurement model, time-to-event, area under the curve analyses), generalized estimating equations (GEE), and ordinal log-linear models (OLLMs). RESULTS: Visualizations of PRO-CTCAE data highlighted different aspects of the data. Selection of the appropriate visualization will depend on the audience and message to be conveyed. Consistent results were obtained by all modeling approaches; no difference was found between dose groups of the DREAMM-2 study in any PRO-CTCAE item by the ToxT approach or the more sophisticated GEE and OLLM methods. Interpretation of GEE results was the most challenging. OLLM supported the interval nature of the PRO-CTCAE response scale in the DREAMM-2 study. All modeling approaches account for multiple testing (driven by the number of items). CONCLUSIONS: Descriptive analyses and longitudinal modeling approaches are complementary approaches to presenting PRO-CTCAE data. In modeling, the ToxT approach may be a good compromise compared with more sophisticated analyses.

Qualitative study to characterize patient experience and relevance of patient-reported outcome measures for patients with metastatic synovial sarcoma.

BACKGROUND: The outlook for patients with metastatic synovial sarcoma (mSS) is poor. Better understanding of patient experience in this setting, beyond clinical measures, may guide improvements in management. Validated patient-reported outcome (PRO) instruments specific to many types of cancer exist, but for rare cancers this is often not the case. METHODS: This study aimed to characterize patient experiences of symptoms and impacts of mSS and evaluate the content validity and relevance of the novel European Organization for Research and Treatment of Cancer Item Library 31 (EORTC IL31) Disease Symptoms PRO tool assessing synovial sarcoma symptoms. This tool comprises items from preexisting, validated cancer-specific PRO instruments from the EORTC Item Library. It was developed as an mSS-specific add-on to the EORTC Quality of Life Questionnaire Core 30 (QLQ-C30), which evaluates general cancer and treatment-related symptoms and functioning. This was a non-interventional, qualitative interview study involving semi-structured, concept elicitation (CE) and cognitive debriefing (CD) telephone interviews in adults with mSS. CE explored symptoms and their impact on functioning and quality of life; CD assessed participant understanding and relevance of the PRO tools. RESULTS: Among the 8 participants, the most common disease-related symptoms reported during CE were fatigue and pain, while shortness of breath was one of the most bothersome. The greatest negative impacts of mSS occurred in domains of physical functioning and sleep. Key treatment priorities for patients were to improve disrupted sleep and ability to undertake strenuous activities. CONCLUSIONS: The interviews showed that, when used together, the EORTC IL31 and EORTC QLQ-C30 covered symptoms and impacts of most relevance and importance to patients with mSS, with no notable gaps and good conceptual coverage. This study therefore supports the content validity of 2 tools in mSS, advocating their use in clinical trials to assess treatment impact on PRO measures of importance to these patients.

Hospital-based surveillance and analysis of genotype variation in Nicaragua after the introduction of the pentavalent rotavirus vaccine.

BACKGROUND: A live, attenuated, pentavalent rotavirus vaccine (RV5) was introduced in Nicaragua in 2006 through a 3-year partnership between Merck & Co, Inc., and the Nicaraguan Ministry of Health. Nicaragua was the first developing nation to include rotavirus vaccine in its national childhood vaccine program. To monitor the possibility of changing circulating rotavirus strains after the introduction of RV5, we determined the genotypes responsible for rotavirus gastroenteritis-related hospitalization during the first 3 postvaccine years. METHODS: Stool samples were collected from children with acute gastroenteritis who presented to any of 6 participating hospitals within 7-14 days of symptom onset. Samples positive for rotavirus antigen were analyzed for P and G genotypes using a reverse transcription polymerase chain reaction method. RESULTS: Overall, the predominant strains were G2P[4] (41.5%), G1P[8] (40.6%), G4P[8] (5.1%) and G3P[8] (4.7%). Strain predominance varied by season. During the 2007 season, G4P[8] (53.2%) and G2P[4] (40.5%) predominated. In the 2008 season, G2P[4] (77.9%) and G1P[8] (12.6%) were predominant, while in the 2009 season, G1P[8] (79.3%) and G3P[8] (7.8%) were predominant. CONCLUSION: No new or unexpected strains were predominant in the years immediately following the introduction of RV5 into Nicaragua. RV5 does not appear to have substantially altered the historical pattern of seasonal fluctuation in rotavirus genotypes.

Effectiveness of vaccination with the pentavalent rotavirus vaccine in Nicaragua as determined using the screening method.

The screening method is a surveillance tool to evaluate vaccine effectiveness (VE) using coverage data on cases and available administrative estimates of vaccine coverage in the population. The aim of this analysis was to evaluate the utility and limitations of using the screening methodology to estimate VE, particularly in a developing world country with a high coverage rate, and to compare it with the VE estimates from 2 case-control studies. Using data from 2008, the screening method employed in this study estimated that VE for 3 doses of RV5 among children<12 mo of age to prevent wild-type severe disease, resulting in hospitalization or emergency department visits, was 92% (95% confidence interval [CI]: 78-100%). Additional sensitivity analysis demonstrated that the point estimates of VE against severe disease ranged from 72% (95% CI: 62-83%) to 92% (95% CI: 78-100%); this range of VE estimates, although wide, is relatively consistent with results reported from 2 case-control studies in Nicaragua for the same time period. When the infrastructure is in place to collect reasonably robust case data, the use of the screening method to estimate VE is possible in the developing world setting. Cases of severe wild-type rotavirus gastroenteritis were obtained through an observational, hospital-based, prospective, surveillance program to assess rotavirus acute gastroenteritis. The proportion of cases vaccinated was estimated using the child's vaccination card or health record. The proportion of the population vaccinated was estimated using administrative population-based vaccination coverage estimates provided by the Nicaraguan Ministry of Health.

Evaluating the health impact of a public-private partnership: to reduce rotavirus disease in Nicaragua.

The purpose of this article is to describe the RotaTeq(®) Nicaragua Partnership and the evaluation of the public health impact of the vaccine conducted by the partners, including the creation of a rotavirus surveillance program and a vaccine effectiveness assessment. The three main objectives of the partnership were to demonstrate that a new rotavirus vaccine could (1) be introduced rapidly in a developing country, (2) be successfully integrated into the existing vaccine delivery infrastructure, and (3) have a significant and measurable public health impact at the end of the 3-y program. The vaccine impact assessment required collaboration among partners with different areas of expertise, including the Nicaraguan Ministry of Health, Merck, local hospitals, government health clinics, laboratories, and a Technical Advisory Group. Through the partnership, RotaTeq(®) became available in a GAVI-eligible developing country, Nicaragua, in the same year it was approved in the United States. Vaccine coverage rapidly reached over > 90% of eligible Nicaraguan children. The impact assessment evaluated over 10,000 subjects and leveraged and enhanced the existing diarrheal surveillance infrastructure, ultimately providing the scientific community with some of the first real-world rotavirus vaccine effectiveness data from a developing country. The successful public-private partnership (PPP) was internationally recognized as a model for the rapid adoption of a new vaccine in a developing world setting. The model could be adapted to benefit other PPPs interested in demonstrating the impact of their own programs.

Case-control study of the effectiveness of vaccination with pentavalent rotavirus vaccine in Nicaragua.

BACKGROUND: In 2006, Merck & Co., Inc., partnered with the Nicaraguan Ministry of Health to demonstrate the public health impact of routine universal vaccination by delivering more than 1.3 million doses of the oral, pentavalent rotavirus vaccine (RV5) in a 3-year period. METHODS: A matched case-control study evaluated the effectiveness of RV5 in reducing the risk for severe wild-type rotavirus gastroenteritis (RGE) resulting in hospitalizations and emergency department visits among children who completed the recommended 3-dose regimen as part of the routine national vaccine program. Cases were identified from 6 hospitals from February 2007 to October 2009 and were age-matched with hospital controls and community controls. Vaccine effectiveness was calculated using conditional logistic regression. RESULTS: Three hundred RGE cases eligible for analysis were matched to 792 hospital and 851 community controls. Vaccine coverage of RV5 in the community reached 92%. Vaccine effectiveness during 2 years of follow-up against severe disease in children receiving 3 doses of RV5 was 87% (95% confidence interval [CI], 74-93) for community controls, 64% (95% CI, 44-78) for hospital controls, and 76% (95% CI, 63-84) when the groups were combined. For the combined groups, vaccine effectiveness was 85% (95% CI, 66-93) among children <12 months old at the time of RGE onset. CONCLUSIONS: The Merck-Nicaragua Rotavirus Vaccine Partnership promoted rapid and widespread uptake of a novel vaccine in a developing country. Vaccine effectiveness was greatest for children younger than 12 months of age who were at the highest risk for severe rotavirus disease.