International validation of two EORTC questionnaires for assessment of health-related quality of life for patients with high-grade non-Hodgkin lymphoma (QLQ-NHL-HG29) and low-grade non-Hodgkin lymphoma (QLQ-NHL-LG20).

BACKGROUND: Health-related quality of life (HRQOL) is a critical aspect to consider when making treatment decisions for patients with non-Hodgkin-lymphoma (NHL). This international study by the European Organisation for Research and Treatment of Cancer (EORTC) tested the psychometric properties of two newly developed measures for patients with high-grade (HG)- and low-grade (LG)-NHL: the EORTC QLQ-NHL-HG29 and the EORTC QLQ-NHL-LG20 to supplement the core questionnaire (EORTC QLQ-C30). METHODS: Overall, 768 patients with HG-NHL (N = 423) and LG-NHL (N = 345) from 12 countries completed the QLQ-C30, QLQ-NHL-HG29/QLQ-NHL-LG20 and a debriefing questionnaire at baseline, and a subset at follow-up for either retest (N = 125/124) or responsiveness to change (RCA; N = 98/49). RESULTS: Confirmatory factor analysis showed an acceptable to good fit of the 29 items of the QLQ-NHL-HG29 on its five scales (symptom burden [SB], neuropathy, physical condition/fatigue [PF], emotional impact [EI], and worries about health/functioning [WH]), and of the 20 items of the QLQ-NHL-LG20 on its four scales (SB, PF, EI, and WH). Completion took on average 10 minutes. Test-retest reliability, convergent validity, known-group comparisons, and RCA find satisfactory results of both measures. A total of 31%-78% of patients with HG-NHL and 22%-73% of patients with LG-NHL reported symptoms and/or worries (e.g., tingling in hands/feet, lack of energy, and worries about recurrence). Patients reporting symptoms/worries had substantially lower HRQOL compared to those without. DISCUSSION: The use of the EORTC QLQ-NHL-HG29 and QLQ-NHL-LG20 questionnaires in clinical research and practice will provide clinically relevant data to better inform treatment decision-making. PLAIN LANGUAGE SUMMARY: The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Group developed two questionnaires. These questionnaires measure health-related quality of life. The questionnaires are for patients with high-grade or low-grade non-Hodgkin lymphoma. They are called the EORTC QLQ-NHL-HG29 and QLQ-NHL-LG20. The questionnaires are now internationally validated. This study demonstrates that the questionnaires are reliably and valid, which are important aspects of a questionnaire. The questionnaires can now be used in clinical trials and practice. With the information gathered from the questionnaires, patients and clinicians can better evaluate treatments and discuss the best choice for a patient.

International validation of the EORTC QLQ-CLL17 questionnaire for assessment of health-related quality of life for patients with chronic lymphocytic leukaemia.

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.

Obinutuzumab Plus Chemotherapy Compared with Rituximab Plus Chemotherapy in Previously Untreated Italian Patients with Advanced Follicular Lymphoma at Intermediate-High Risk: A Cost-Effectiveness Analysis.

OBJECTIVE: To assess the cost-effectiveness of obinutuzumab (O-chemo) in comparison to rituximab (R-chemo) in patients with untreated advanced follicular lymphoma (FL) at intermediate or high risk from an Italian National Health Service (NHS) perspective. METHODS: A previously developed four-state Markov model was adapted to estimate lifetime clinical outcomes and costs of Italian patients with advanced FL and an FL international predictive index score ≥2 in treatment with O-chemo and R-chemo. Life expectancy was derived from the GALLIUM and PRIMA clinical trials. Progression-free survival (PFS), early progressive disease (PD), and treatment duration were extrapolated by fitting parametric distributions to empirical data in GALLIUM and late PD to data in PRIMA. Expected survival was weighed by published utilities. Costs updated to 2020 Euros and health gains occurring after the first year were discounted at an annual 3% rate. Probabilistic sensitivity analysis (PSA) was carried out. RESULTS: O-chemo was associated with an incremental survival increase (0.97 life-years [LYs]), even when weighted for quality (0.88 quality-adjusted LYs [QALYs]), and incremental costs (around €15,000), driven by longer treatment during PFS state relative to R-chemo. The incremental cost-effectiveness ratio and incremental cost-utility ratio are both widely accepted by the Italian NHS (around €15,500/LY and €17,000/QALY gained, respectively). PSA simulations confirmed the robustness of results given sensible variations in assumptions. CONCLUSION: O-chemo has superior clinical efficacy compared to rituximab, and should be considered a cost-effective option in first-line treatment of patients with advanced FL at intermediate or high risk in Italy. Incremental cost-effectiveness ratios are below the threshold considered affordable by developed countries.

Venetoclax: a real game changer in treatment of chronic lymphocytic leukemia.

Venetoclax - a novel, orally bioavailable inhibitor of B-cell lymphoma-2 - has demonstrated substantial clinical activity in the treatment of chronic lymphocytic leukemia. Alone or in combination with other targeted agents, venetoclax results in high rate of durable responses and undetectable measurable residual disease. The peculiarity of venetoclax is that it allows for fixed durations of therapy of 12 months in the frontline and 24 months in the relapsed/refractory setting, with a favorable impact on compliance and pharmacoeconomics. This approach implies a change of therapeutic paradigm in chronic lymphocytic leukemia from continuous to time-fixed therapy. Nowadays, it remains challenging to identify patients suitable for the optimal approach. Clinical trials addressing the issue of continuous versus time-limited therapy are ongoing.

Rituximab in the management of acute lymphoblastic leukemia.

INTRODUCTION: The anti-CD20 chimeric monoclonal antibody rituximab has revolutionized the treatment of B-cell malignancies, significantly improving patient clinical outcome. Recently, some single-group studies have suggested that adding rituximab to chemotherapy can improve the outcome of CD20-positive B-cell acute lymphoblastic leukemia (ALL) patients. Areas covered: An overview of the current insights of rituximab in adult ALL patients is presented here. In particular, we focused on results of multicenter randomized phase III trial (GRAALL-2005 - Group for Research on Adult Acute Lymphoblastic Leukemia) that evaluated the benefit of associating rituximab to chemotherapy in Ph-negative, B-lineage ALL expressing the CD20 antigen. Expert opinion: Data from clinical trials confirm that rituximab enhances the efficacy of chemotherapy without additive toxicity in ALL. However, results of GRAAL 2005 study represent only a modest incremental improvement in the treatment of ALL. Other promising compounds as single agent or in combination with chemotherapy are currently in different stages of clinical development. The GRAALL 2005 study sets the stage for other prospective studies which will further elucidate the role of monoclonal antibodies in the management of ALL.

Treatment of elderly patients with chronic lymphocytic leukemia: an unmet cinical need.

In chronic lymphocytic leukemia (CLL), the most prevalent lymphoid malignancy in western countries, patients have a median age at diagnosis of 72 years. In the last few years, there has been remarkable progress in understanding the biology of CLL, the detection of molecular prognostic factors and the development of more effective therapies. However, many of the milestone studies were conducted in populations that were considerably younger than the average age of the CLL population. Today, the challenge is to improve management of elderly patients. In this population, outcome of treatment with newer highly effective therapies is often compromised by comorbidities and poor performance status. Decision on how elderly patients should be treated is thus a complex issue. The management of these patients should rely on the development of risk-stratified treatment strategies based on the assessment of individual functional status and the biologic characteristics of CLL. New single agents with reduced toxic effects (i.e., inhibitors of BCR signalling) that have achieved promising results in Phase I/II studies when available should modify the paradigm of the treatment of elderly patients with CLL.

Health-related quality of life assessment and reported outcomes in leukaemia randomised controlled trials - a systematic review to evaluate the added value in supporting clinical decision making.

Health-related quality of life (HRQOL) is increasingly reported as an important outcome in cancer clinical trials. However, very little evidence exists on the impact of such evaluation in randomised controlled trials (RCTs) of leukaemia patients. A systematic search of the literature from 1980 to 2007 was undertaken and studies were identified and evaluated independently, according to a pre-defined coding scheme, by three reviewers. Both HRQOL outcomes and traditional clinical reported outcomes were systematically analysed to evaluate their consistency and their relevance for supporting clinical decision making. Nine RCTs were identified, involving 3838 patients overall. There were four RCTs involving acute myeloid leukaemia patients (AML), three with chronic myeloid leukaemia (CML) and two with chronic lymphocytic leukaemia (CLL). Six studies were published after 2000 and provided fairly robust methodological quality. Imatinib greatly improved HRQOL compared to interferon based treatments in CML patients and fludarabine plus cyclophosphamide does not seem to have a deleterious impact on patient's HRQOL when compared to fludarabine alone or chlorambucil in CLL patients. This study revealed the paucity of HRQOL research in leukaemia patients. Nonetheless, HRQOL assessment is feasible in RCTs and has the great potential of providing valuable outcomes to further support clinical decision making.