Non-cirrhotic thrombocytopenic patients with hepatitis C virus: characteristics and outcome of antiviral therapy.

Background and Aim: Thrombocytopenia is frequently observed in patients with chronic hepatitis C virus (HCV) infection and cirrhosis, although it can also be observed in patients without cirrhosis by a virus-mediated phenomenon. This study assessed the prevalence, characteristics, and outcomes of antiviral therapy in patients with chronic HCV infection and thrombocytopenia not associated with cirrhosis. Methods: The study included 1268 patients with HCV infection and thrombocytopenia enrolled in the phase 3 ENABLE studies that assessed the impact of eltrombopag on achieving a sustained virologic response to pegylated interferon and ribavirin. The study population was subdivided according to baseline FibroSURE test results into patients with non-cirrhosis (FibroSURE < 0.4) and cirrhosis-related (FibroSURE 65 0.75) thrombocytopenia. Results: Compared with patients with cirrhosis-related thrombocytopenia (n = 995; 78.5%), non-cirrhotic patients with thrombocytopenia (n = 59; 4.6%) were younger (mean age [95% confidence interval (CI)]: 43.9 [40.7\u201347.2] vs 52.7 [52.2\u201353.3] years; P < 0.0001), predominantly female (64% [51\u201376] vs 30% [27\u201333]; P < 0.0001), and less frequently had a Model for End-Stage Liver Disease score 65 10 (24% [14\u201337] vs 45% [42\u201349]; P = 0.0012), low albumin levels ( 64 35 g/L; 2% [0\u20139] vs 32% [29\u201335]; P < 0.0001), and prevalence of diabetes mellitus (3% [0\u201312] vs 21% [19\u201324]; P = 0.0005). The sustained virologic response rate was higher in non-cirrhotic patients with thrombocytopenia (46% [95% CI, 33\u201359] vs 16% [14\u201318]; P < 0.0001). Conclusions: Patients with thrombocytopenia associated with HCV who have lower FibroSURE test results may have better preserved liver function and higher sustained virologic response rates than patients with cirrhosis

Outcomes by Cardiac Stage in Patients With Newly Diagnosed AL Amyloidosis: Phase 3 ANDROMEDA Trial

BACKGROUND: Patients with amyloid light chain amyloidosis and severe cardiac dysfunction have a poor prognosis. Treatment options that induce rapid and deep hematologic and organ responses, irrespective of cardiac involvement, are needed. OBJECTIVES: The aim of this study was to evaluate the impact of baseline cardiac stage on efficacy and safety outcomes in the phase 3 ANDROMEDA trial. METHODS: Rates of overall complete hematologic response and cardiac and renal response at 6 months and median major organ deterioration–progression-free survival and major organ deterioration–event-free survival were compared across cardiac stages (I, II, or IIIA) and treatments (daratumumab, bortezomib, cyclophosphamide, and dexamethasone [D-VCd] or bortezomib, cyclophosphamide, and dexamethasone [VCd]). Rates of adverse events (AEs) were summarized for patients with and without baseline cardiac involvement and by cardiac stage. RESULTS: Median follow-up duration was 15.7 months. The proportions of stage I, II, and IIIA patients were 23.2%, 40.2%, and 36.6%. Across cardiac stages, hematologic and organ response rates were higher and major organ deterioration–progression-free survival and major organ deterioration–event-free survival were longer with D-VCd than VCd. AE rates were similar between treatments and by cardiac stage; serious AE rates were higher in patients with cardiac involvement and increased with increasing cardiac stage. The incidence of cardiac events was numerically greater with D-VCd vs VCd, but the rate of grade 3 or 4 events was similar. The exposure-adjusted incidence rate for cardiac events was lower with D-VCd than VCd (median exposure 13.4 and 5.3 months, respectively). CONCLUSIONS: These findings demonstrate the efficacy of D-VCd over VCd in patients with newly diagnosed amyloid light chain amyloidosis across cardiac stages, thus supporting its use in patients with cardiac involvement. (NCT03201965

Daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with newly diagnosed AL amyloidosis: subgroup analysis of ANDROMEDA

Subcutaneous daratumumab plus bortezomib/cyclophosphamide/dexamethasone (VCd; D-VCd) improved outcomes versus VCd for patients with newly diagnosed immunoglobulin light-chain (AL) amyloidosis in the phase 3 ANDROMEDA study. We report a subgroup analysis of Asian patients (Japan; Korea; China) from ANDROMEDA. Among 388 randomized patients, 60 were Asian (D-VCd, n = 29; VCd, n = 31). At a median follow-up of 11.4 months, the overall hematologic complete response rate was higher for D-VCd versus VCd (58.6% vs. 9.7%; odds ratio, 13.2; 95% confidence interval [CI], 3.3–53.7; P < 0.0001). Six-month cardiac and renal response rates were higher with D-VCd versus VCd (cardiac, 46.7% vs. 4.8%; P = 0.0036; renal, 57.1% vs. 37.5%; P = 0.4684). Major organ deterioration progression-free survival (MOD-PFS) and major organ deterioration event-free survival (MOD-EFS) were improved with D-VCd versus VCd (MOD-PFS: hazard ratio [HR], 0.21; 95% CI, 0.06–0.75; P = 0.0079; MOD-EFS: HR, 0.16; 95% CI, 0.05–0.54; P = 0.0007). Twelve deaths occurred (D-VCd, n = 3; VCd, n = 9). Twenty-two patients had baseline serologies indicating prior hepatitis B virus (HBV) exposure; no patient experienced HBV reactivation. Although grade 3/4 cytopenia rates were higher than in the global safety population, the safety profile of D-VCd in Asian patients was generally consistent with the global study population, regardless of body weight. These results support D-VCd use in Asian patients with newly diagnosed AL amyloidosis. ClinicalTrials.gov Identifier: NCT03201965