L'Italia come modello per l'Europa e per il mondo nelle politiche sanitarie per il trattamento dell'epatite cronica da HCV

The World Health Organization foresees the elimination of HCV infection by 2030. In light of this and the curre nt, nearly worldwide, restriction in direct-acting agents (DAA) accessibility due to their high price, we aimed to evaluate the cost-effectiveness of two alternative DAA treatment policies: Policy 1 (universal): treat all patients, regardless of the fibrosis stage; Policy 2 (prioritized): treat only priori tized patients and delay treatment of the remaining patients until reaching stage F3. T he model was based on patient’s data from the PITER cohort. We demonstrated that extending HC V treatment of patients in any fibrosis stage improves health outcomes and is cost-effective

Economic consequences of investing in anti-HCV antiviral treatment from the Italian NHS perspective : a real-world-based analysis of PITER data

OBJECTIVE: We estimated the cost consequence of Italian National Health System (NHS) investment in direct-acting antiviral (DAA) therapy according to hepatitis C virus (HCV) treatment access policies in Italy. METHODS: A multistate, 20-year time horizon Markov model of HCV liver disease progression was developed. Fibrosis stage, age and genotype distributions were derived from the Italian Platform for the Study of Viral Hepatitis Therapies (PITER) cohort. The treatment efficacy, disease progression probabilities and direct costs in each health state were obtained from the literature. The break-even point in time (BPT) was defined as the period of time required for the cumulative costs saved to recover the Italian NHS investment in DAA treatment. Three different PITER enrolment periods, which covered the full DAA access evolution in Italy, were considered. RESULTS: The disease stages of 2657 patients who consecutively underwent DAA therapy from January 2015 to December 2017 at 30 PITER clinical centres were standardized for 1000 patients. The investment in DAAs was considered to equal €25 million, €15 million, and €9 million in 2015, 2016, and 2017, respectively. For patients treated in 2015, the BPT was not achieved, because of the disease severity of the treated patients and high DAA prices. For 2016 and 2017, the estimated BPTs were 6.6 and 6.2 years, respectively. The total cost savings after 20 years were €50.13 and €55.50 million for 1000 patients treated in 2016 and 2017, respectively. CONCLUSIONS: This study may be a useful tool for public decision makers to understand how HCV clinical and epidemiological profiles influence the economic burden of HCV

Rituximab plus liposomal pegylated doxorubicin in the treatment of primary cutaneous B-cell lymphomas

Background: In primary cutaneous B-cell lymphomas (PCBCL), radiotherapy - or surgery in a minority of cases - is the first-line treatment in follicle center lymphoma (PCFCL) and marginal zone B-cell lymphoma (PCMZL). Conversely, patients with multifocal skin involvement or relapsed/refractory disease deserve a systemic chemotherapy. In diffuse large B-cell lymphoma, leg type (PCLBCL-LT), due its poorer outcome, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-like regimens are the most commonly used frontline, although hard to propose in elderly patients. In this regard, the association of rituximab (R) and pegylated liposomal doxorubicin (PLD) can be considered a promising, alternative approach. Aims: Based on the favorable results reported with R and PLD in several recent trials, we decided to test efficacy and safety of this combination. Methods: Twelve patients with PCBCL were treated with R plus PLD, and 7 had relapsed disease. Treatment plan consisted of 2 monthly cycles of R 375 mg/m2 and PLD 20 mg/m2 day 1;15, followed (in responders) by two cycles given only at day 1. All patients received prophylactic pyridoxine to prevent palmar-plantar erythrodysesthesia (PPE). Results: Ten of 12 patients had a response (eight complete; two partial), remarkably 2/3 with PCLBCL-LT. Two patients did not respond (one progressive disease, PD, and one stable disease). Three patients died after a median follow-up of 56 months, two patients due to PD, and 1 due to a second neoplasm. Two out of 10 responders relapsed after 31 and 32 months, respectively. Hematological toxicity was negligible (one case of grade 2 neutropenia), as well as extra-hematological toxicity (two cases of grade 2 PPE). Conclusions: These preliminary data suggest that R-PLD is effective and well tolerated in all subsets of PCBCL and may be offered frontline in indolent cases unsuitable for radiotherapy or surgery as well as in more aggressive cases with contraindications to CHOP-like regimens

RITUXIMAB-CHOP14 SEEMS TO OVERCOME THE NEGATIVE PROGNOSTIC SIGNIFICANCE OF B CELL ORIGIN IN DLBCL LYMPHOMA PATIENTS

Diffuse large B cell lymphoma (DLBCL) is the most common types of non-Hodgkin’s lympoma. Approximately half of all patients (pts) will be cured of their disease by primary therapy. Two major subgroups were identified by gene expression profiling: germinal centre B (GC) cell or non-germinal centre (non-GC). The GC group showes a significantly better survival than the non-GC group. Immunohistochemistry has been evaluated as a surrogate for this molecular classification. The aim of this study was to define retrospectively the B-cell origin of 40 pts treated with R-CHOP14 and to evaluate if the dose-dense therapy could improve clinical outcome. We performed a centralized immunohistochemical stains on formalin-fixed paraffin-embedded tissues from diagnostic biopsies with the following antibodies: CD10, bcl-6, bcl-2, MUM1 and Mib1. Based on the published algorithm we subdivided the pts in GCB and non-GCB origin. We evaluated also the prognostic value of single protein expression. Twenty-seven pts were male, 22 stage III-IV, 17 presented symptoms at diagnosis 22 showed abnormal LDH value, the IPI was intermediate-high risk or high risk in 13 pts. According to immunohistochemistry analysis 16 pts derived from GC and 24 from non-GC, 12 pts presented a positive CD10, 30 a positivity for bcl6, 19 a positive bcl2 and 27 a positive MUM1. Twenty-nine pts (73%) obtained a complete remission (CR), 8 a partial response (PR) and 3 were non responders (NR). Four out 29 CR pts experienced relapse, three (75%) derived from nonGC. Eight pts died, 4 derived from GC and 4 from non-GC. After a median period of observation of 18 months (range 3-72) the overall survival (OS) was 75% and the failure free survival (FFS) was 57%. The statistical analysis was performed comparing the B cell origin and clinical characteristics, moreover was also evaluated the expression of bcl2 either in GC or in non-GC lymphomas. In univariate analysis normal Beta2 microglobulin and low-intermediate risk IPI were significantly associated with longer overall survival. In univariate and multivariate analysis FFS was significantly higher in low and low-intermediate IPI risk pts. No differences were reported in OS and FFS evaluating the B cell origin. In conclusion we can point out that the intensification could enhance the efficacy of R-CHOP regimen improving the overall survival and FFS in pts with non-GC lymphoma. In this analysis the only significance was the IPI index that affected either OS or FFS