Chronic graft versus host disease (cGVHD) is a debilitating and costly complication following haemopoietic stem cell transplantation (HSCT). This study describes the economic burden associated with cGVHD. Direct costs associated with specialised healthcare utilisation (inpatient admissions and outpatient visits), as well as indirect costs associated with sickness absence-associated productivity loss were estimated in patients who underwent allogeneic HSCT in Sweden between 2006 and 2015, linking population-based health and economic registers. To capture the period of chronic GVHD, patients were included who survived > 182 days post-HSCT (start of follow-up), and cGVHD was classified based on patient treatment records to correct for any diagnosis underreporting. Patients were classified as ‘non-cGVHD’ if they received no immunosuppressive treatment, ‘mild cGVHD’ if they received only systemic corticosteroid treatment or immunosuppressive treatment, or ‘moderate–severe cGVHD’ if they received extracorporeal photopheresis (ECP) only, corticosteroid treatment and immunosuppressive treatment, or systemic corticosteroid treatment and ECP treatments. Patients with moderate–severe cGVHD spent more time in healthcare, had higher healthcare resource costs and higher sickness absence-related productivity loss compared to patients with non- or mild cGVHD. The cumulative total costs during the first 3 years of follow-up were EUR 14,887,599, EUR 20,544,056, and EUR 47,811,835 for non-, mild, and moderate–severe groups, respectively. The long-term costs incurred with cGVHD following HSCT continue to be very high and significantly impacted by cGVHD severity. This study adds real-world health resource and economic insight relevant for policy-makers and healthcare providers when considering the clinical challenge of balancing immunosuppression to reduce cGVHD.

Aim:A systematic literature review and network meta-analysis were conducted to determine the relative efficacy and safety of interventions for treatment-naive chronic lymphocytic leukemia patients, as comparative evidence is scarce. Materials & methods: Relative treatment effects of progression-free survival, overall survival and safety outcomes were estimated via network meta-analysis based on data identified via systematic literature review. Results: Ibrutinib was superior in all pairwise comparisons for progressionfree survival (probability to be better [P] range: overall population: 69-100%; fludarabine-ineligible population: 69-100%) and overall survival (P range: overall: 89-100%; fludarabine-ineligible: 91-100%) and had the highest probability of being best for all outcomes. Conclusion: Ibrutinib provides superior benefit in survival and safety compared with other front-line treatments of chronic lymphocytic leukemia. Chronic lymphocytic leukemia (CLL) is the most common hematologic malignancy in western countries and occurs mainly in older people. Overall, 4.2 per 100,000 population per year develop the condition, a figure that rises to over 30 per 100,000 per year among those aged over 80 years [1]. The overall 5-year survival rate for people with CLL is 83%, although survival varies widely according to disease stage [2]. Treatment for CLL has evolved rapidly over the past two decades, with the addition of CD20-targeted antibodies, B-cell lymphoma-2 (BCL-2)-targeted treatment and B-cell receptor-targeted treatment resulting in improved outcomes [3][4].As indicated by both the European Society for Medical Oncology (ESMO) and the National Comprehensive Cancer Network [1,5], there are various management options for CLL, and treatment choices must account for key patient and disease characteristics known to affect therapeutic outcomes. These include patient age [6], fitness/comorbidities [7] and molecular cytogenetics [6,8]. Generally, for fit patients with advanced, symptomatic disease, the so-called 'full-dose fludarabine-based' regimen of fludarabine + cyclophosphamide + rituximab (FCR) is recommended [1]. However, for elderly patients and/or those with significant comorbidities, FCR is associated with significant risk of myelosuppression and severe infection [9]. Options are further limited if these individuals also have cytogenetic characteristics associated with poor outcomes from current treatments (such as 17p or 11q deletion, or absence of IgVH mutation). For these patients, ESMO and National Comprehensive Cancer Network guidelines recommend ibrutinib monotherapy [1,5,9].Given the range of CLL treatment options for people with differing levels of fitness, and the dearth of head-tohead clinical trials comparing front-line treatments, there remains considerable uncertainty regarding the optimal regimen for each patient group. The objectives of the presented systematic literature review (SLR) and network meta-analyses (NMAs) were therefore to determine the relative efficacy and safety of intervention...

IntroductionIbrutinib (ibr) monotherapy and the combination of obinutuzumab plus chlorambucil (obi) are approved for previously untreated chronic lymphocytic leukemia (CLL). No trials directly comparing their efficacy are available. Therefore a matching-adjusted indirect comparison (MAIC) was performed to provide insight into their relative efficacy in terms of progression-free survival (PFS) and overall survival (OS). MAIC attempts to adjust for between-trial differences in factors known or suspected to influence treatment effects, to minimize bias.MethodsA MAIC within a Bayesian framework was conducted using individual patient data from the RESONATE-2 study of ibr versus chlorambucil and published data from the CLL11 study of obi versus chlorambucil. Both studies were conducted in patients ineligible for full-dose fludarabine-based therapy. After matching, the reweighted adjusted relative efficacy measure of ibr versus chlorambucil from RESONATE-2 [hazard ratio (HR), 95% credible interval (CrI)] was compared with that of obi versus chlorambucil from CLL11 for each endpoint, using a Bayesian indirect comparison.ResultsOur results suggest that in a population with similar average baseline characteristics to CLL11, ibr would improve PFS and OS outcomes compared to obi. Before matching, the HRs for ibr versus obi were 0.48 [CrI = 0.22–1.02, p(HR <1) = 97%], 0.85 [CrI = 0.44–1.63, p(HR <1) = 69%], and 0.40 [CrI = 0.10–1.54, p(HR <1) = 91%] for PFS by investigator assessment, PFS by independent review committee, and OS, respectively. After matching on all available characteristics the HRs decreased to 0.12 [CrI = 0.02–0.97, p(HR <1) = 98%], 0.24 [CrI = 0.04–1.35, p(HR <1) = 95%], and 0.21 [CrI = <0.01–8.89, p(HR <1) = 79%], respectively. There was a large variance around the treatment effect for OS due to the low number of deaths.ConclusionOur analysis suggests that ibrutinib is highly likely to provide greater PFS benefit than obinutuzumab plus chlorambucil in older or less fit patients with previously untreated CLL. There is also an indication of improvement in OS, albeit with a higher uncertainty due to the low number of events.FundingJanssen-Cilag Ltd.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-017-0564-1) contains supplementary material, which is available to authorized users.

The use of novel agents is predicted to yield substantive gains in predicted lifetime OS and QALY improvements compared to traditional therapies in CLL patients who are ineligible for fludarabine-based chemoimmunotherapy.

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