Search

Background: Cytomegalovirus (CMV), a common post‐transplant infection, is associated with increased healthcare resource utilization. In the Phase 3 SOLSTICE trial, maribavir was superior to investigator‐assigned therapy (IAT; valganciclovir/ganciclovir, foscarnet, and cidofovir) for CMV viremia clearance at Week 8 in transplant recipients with confirmed refractory CMV infection with/without resistance. This exploratory analysis evaluated hospital admissions of patients during the SOLSTICE trial. Methods: Patients were randomized to maribavir (400 mg twice daily) or IAT for an 8‐week treatment phase with a 12‐week follow‐up. After ≥3 weeks of treatment, patients on IAT who met pre‐specified criteria could enter a maribavir rescue arm (8‐week maribavir treatment, 12‐week follow‐up). Adjusted hospitalization rates and length of hospital stay (LOS) were estimated using negative binomial models adjusting for the time in the relevant study phase. Subgroup analysis for the maribavir rescue arm was conducted. Results: Overall, 352 patients were randomized (maribavir: 235; IAT: 117); 22 entered the maribavir rescue arm. After adjusting for treatment exposure, patients on maribavir had a 34.8% reduction in hospitalization rate and 53.8% reduced LOS (days/person/year) versus IAT during the treatment phase. No significant differences between treatments were observed during the follow‐up phase, although in both arms, hospitalization rates were lower than in the treatment phase. In the maribavir rescue arm, hospitalizations were 60.6% lower on/after maribavir rescue versus pre‐rescue treatment (p = 0.008). Conclusion: In patients requiring post‐transplant CMV treatment, hospitalization rate and LOS were lower for maribavir than IAT, and hospitalization rates were lower on/after maribavir rescue than pre‐rescue. Reducing hospitalizations can alleviate the burden on patients and healthcare systems. [ABSTRACT FROM AUTHOR]

Background: We aimed to estimate minimally important difference (MID) for interpreting group‐level change over time for European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ‐C30) scores in head and neck cancer. Methods: Data were derived retrospectively from two published EORTC trials. Clinical anchors were selected using correlation strength and clinical plausibility of the given anchor/QLQ‐C30 scale pair. MIDs for within‐group and between‐group change were estimated via the mean change method and linear regression, respectively. Distribution‐based MIDs were also examined. MIDs for two of the scales, dyspnea and nausea/vomiting, are more uncertain considering their low correlations with the anchors. Results: Anchor‐based MIDs could be determined for deterioration in 7 of the 14 QLQ‐C30 scales assessed, and in 3 scales for improvement. MIDs varied by scale, direction of change, and anchor. Absolute MID values ranged from 5 to 15 points for within‐group change and 4 to 12 for between‐group change. Most MIDs were within 4 to 10 points. Conclusions: Our findings, if confirmed, will aid interpreting changes in selected QLQ‐C30 scale scores over time and inform sample size calculations in future clinical trials in head and neck cancer. [ABSTRACT FROM AUTHOR]

Objectives: Thresholds for the minimally important difference (MID) or responder definition (RD) in health‐related quality‐of‐life (HRQoL) scores are required to interpret the impact of an intervention or change in the trajectory of the condition which is meaningful to patients. This study aimed to establish MID and RD for the European Organisation for Research and Treatment of Cancer Quality of Life Multiple Myeloma questionnaire (EORTC QLQ‐MY20). Methods: A novel mixed‐methods approach was applied by utilizing both existing clinical trial data and prospective patient interviews. Anchor‐based, distribution‐based, and qualitative‐based estimates of meaningful change were triangulated to form recommended RDs for each scale of the EORTC QLQ‐MY20. Anchor‐based MIDs were summarized using weighted correlation. Results: Recommended MIDs were as follows: Disease Symptoms (DS 10 points), Side Effects of Treatment (SE 10 points), Body Image (BI 13 points), and Future Perspective (FP 9 points). Recommended RDs were as follows: DS (16 improvement; 11 worsening), SE (6 improvement; 9 worsening), BI (33 improvement; 33 worsening), and FP (11 improvement; 11 worsening). Conclusions: The study generated estimates of the MID and RD for each scale of the EORTC QLQ‐MY20. Published estimates will enable investigators and clinicians to adopt these as standard for interpretation and for hypothesis testing. Consequently, analyses from trials of different interventions can be more comparable. [ABSTRACT FROM AUTHOR]

Combination fludarabine (F), cyclophosphamide (C) and rituximab (R) is the standard front-line therapy in chronic lymphocytic leukaemia (CLL), but appropriate treatment of relapsed/refractory CLL is less clear. Combined FC and mitoxantrone (M) has been reported to be effective in a single arm study, and rituximab when added to chemotherapy in CLL is synergistic. A randomized, two-stage, Phase II trial of FCM and FCM-R was conducted in relapsed CLL. The primary endpoint was response rate 2 months after therapy, assessed according to the 2008 International Workshop CLL criteria. In addition, minimal residual disease (MRD) in the marrow was studied 2 months after therapy, with MRD negativity defined as <0·01% CLL cells. Fifty-two patients were entered, 26 in each arm. The overall response rates to FCM and FCM-R were 58% and 65% respectively. Combined complete response (CR) and CR with incomplete marrow recovery [CR(i)] was 15% (95% confidence interval [CI]:4-35%) for FCM and 42% (95%CI:23-63%) for FCM-R, with eight patients achieving MRD negativity (3 FCM; 5 FCM-R). The toxicity of both regimens was acceptable. In conclusion, the addition of rituximab to FCM improves the response rates in relapsed CLL, resulting in more complete remissions and without additional safety concerns. Efficacy and safety should be fully tested in a randomized Phase III trial. [ABSTRACT FROM AUTHOR]

We examined the effects of active untreated chronic lymphocytic leukaemia (CLL) on health-related quality of life (HRQoL), measured by the European Organization for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) at randomisation into the Leukaemia Research Fund CLL4 trial. Patients were scored 0–100 within each of 15 domains. A difference between groups of ≥10 points was deemed clinically significant (asterisked * below). 431 valid baseline questionnaires were returned. Compared with population norms, patients had impaired HRQoL in 13/15 domains. The greatest differences were in fatigue*, sleep disturbance*, role functioning and global HRQoL. Fatigue was reported by 81% of patients, compared with the next most common symptoms: sleep disturbance (56%) and dyspnoea (49%). There was no association between spleen, liver or lymph node enlargement, or lymphocytosis and any HRQoL domain. Older age (≥70 years) was associated with poorer physical functioning ( P < 0·001) but fewer financial difficulties ( P < 0·001*). Impairment of HRQoL at baseline was most apparent in stage A-progressive patients with B-symptoms and stage C patients with haemoglobin <120 g/l: compared with all others, these patients had poorer physical, role and social functioning, more fatigue and dyspnoea and poorer global HRQoL (all P ≤ 0·001*). These findings support the recommendation to begin treatment when patients experience symptomatic disease, to improve HRQoL. [ABSTRACT FROM AUTHOR]

Thalidomide maintenance has unresolved issues regarding dosage and toxicity. We evaluated this in five dose cohorts in 100 patients. At a median follow-up of 32·3 months, 23 patients had stopped thalidomide for disease progression, 54 for side effects. 3-year overall and progression-free survival was 76% and 41% respectively. Dosage did not influence disease outcome but greatly affected toxicity. Fifteen patients converted from partial remission to complete remission on thalidomide at a median of 13·5 months. Maintenance doses >200 mg were largely unachievable and peripheral neuropathy was the main toxicity. Lower doses enabled more patients to stay on the drug for a useful period of time. [ABSTRACT FROM AUTHOR]

This study aimed to explore the relationship between pain mechanism, pain intensity, and leg ulcer characteristics using a 6-month longitudinal cohort study in a community setting in the north of England. Patients with leg ulceration referred consecutively to district nurses were invited to participate ( n=96). The main outcome measures were pain intensity using daily visual analogue scores, leg ulcer characteristics (etiology, size, location, duration), and LANSS (Leeds Assessment of Neuropathic Symptoms and Signs). Results suggested that type, duration, position, and size of the leg ulcer had no effect on average daily pain scores. Using the LANSS questionnaire, 43.5% of respondents reported symptoms suggestive of a neuropathic mechanism to their pain. Patients with neuropathic symptoms had higher average daily pain scores ( p<0.001). Fewer people had healed ulcers at 6 months with neuropathic symptoms compared with those with no neuropathic symptoms (30.8 vs. 52.1%). It would seem that the severity of pain can not be predicted by the type, size, position, or duration of ulceration. Patients who scored positively for neuropathic symptoms had higher average daily pain scores and fewer had healed leg ulcers at 6 months compared with those who did not experience neuropathic signs and symptoms. [ABSTRACT FROM AUTHOR]

Selecting the most appropriate chronic lymphocytic leukaemia (CLL) treatment is challenging. Patient-reported health-related quality of life (HRQoL) is therefore a critical aspect to consider. This international study by the European Organization for Research and Treatment of Cancer (EORTC) tested the psychometric properties of a newly developed measure for CLL patients: the EORTC QLQ-CLL17 to supplement the core questionnaire (EORTC QLQ-C30). Patients with CLL (n = 341) from 12 countries completed the QLQ-C30, QLQ-CLL17 and a debriefing questionnaire. Sociodemographic and clinical data were recorded from medical records. A high percentage (30%-66%) reported symptoms and/or worries (e.g. aches/pains in muscles, lack of energy and worry/fears about health). Confirmatory factor analysis showed an acceptable to good fit of the 17 items on the three scales (i.e. symptom burden, physical condition/fatigue and worries/fears about health and functioning). Completion took on average 8 min. Test-retest and convergent validity was demonstrated. The QLQ-CLL17 differentiated between patients with an Eastern Cooperative Oncology group (ECOG) performance of 0 versus 1-3 (p's < 0.01 and clinically relevant). The newly developed EORTC QLQ-CLL17 will increase sensitivity of HRQoL assessment in patients with CLL. Implementation of this questionnaire both in clinical research and practice will help to generate unique clinically relevant data to better inform CLL treatment decision-making., (© 2022 British Society for Haematology and John Wiley & Sons Ltd.)