A Novel X-Linked Inhibitor of Apoptosis Deficient Variant Showing Attenuated Epstein-Barr Virus Response.

We report on 2 Asian siblings with X-linked inhibitor of apoptosis deficiency that arose from a novel deletion that presented with Epstein-Barr virus disease and hemophagocytic lymphohistiocytosis. This disease is ascribed to dysfunction in the nucleotide binding and oligomerization domain receptor pathway, tested using a modified muramyl dipeptide-mediated assay.

The Effectiveness of Tyrosine Kinase Inhibitors and Molecular Monitoring Patterns in Newly Diagnosed Patients With Chronic Myeloid Leukemia in the Community Setting.

BACKGROUND: Clinical outcomes of patients with chronic myeloid leukemia (CML) treated in clinical trials, including response to therapy, may not be representative of those treated in a community setting. Thus, we sought to determine the real-world effectiveness of first-line tyrosine kinase inhibitors in CML by evaluating response rates, all-cause discontinuation, and adherence. Response monitoring patterns were also analyzed. PATIENTS AND METHODS: This retrospective observational study, using the McKesson Specialty Health/US Oncology Network (MSH/USON) iKnowMed electronic health record database and medical charts, identified newly diagnosed CML patients who received first-line imatinib, dasatinib, or nilotinib from July 2007 to March 2011, and were then followed for ≥ 18 months. RESULTS: Three hundred patients met study criteria (222 imatinib-treated, 34 dasatinib-treated, and 44 nilotinib-treated in the first-line). Molecular and cytogenetic response assessments were conducted less frequently than recommended (40% never had cytogenetic or molecular monitoring at any time). Patients treated with either dasatinib or nilotinib experienced higher response rates by 6, 12, and 18 months, faster time to major molecular response, and a significantly lower rate of all-cause treatment discontinuation within 18 months relative to imatinib-treated patients. Approximately 56% of all patients were adherent to tyrosine kinase inhibitor therapy. CONCLUSION: Dasatinib and nilotinib were more effective than imatinib as first-line therapy for CML in a community setting, as observed in descriptive and univariate analyses. The frequency of cytogenetic and molecular monitoring was lower than that recommended by current guidelines, including patients with no molecular or cytogenetic assessments during the 18-month follow-up. Therefore, MSH/USON is working toward improving compliance with response monitoring guidelines.

Economic impact of disease progression following front-line therapy in classical Hodgkin lymphoma.

The current study aimed to assess the economic burden of progressive disease among patients with Hodgkin lymphoma (HL) receiving second- or third-line therapy in a large US network of community-based practices. This retrospective, observational cohort analysis used electronic health records to examine adult patients with classical HL who received chemotherapy between 2007 and 2011. Of 291 observations, 112 had non-progressive disease (received only one line of therapy; LOT1), 114 received second-line therapy (LOT2), and 65 received third-line therapy (LOT3). In LOT2, 49 patients (43%) underwent transplant. In LOT3, 13 patients (20%) underwent transplant. The mean total cost per line of therapy was $21 956 in LOT1, $77 219 in LOT2, and $59 442 in LOT3. When transplant was required, the mean total cost per line of therapy increased 7- to 8-fold when compared with the cost of LOT1 (approximately $154 000 for LOT2 and $193 000 for LOT3). Future therapies that intervene as early as possible in the treatment algorithm to prevent or significantly delay relapse will likely result in significant cost savings.

Sequencing of Cabazitaxel and Abiraterone Acetate After Docetaxel in Metastatic Castration-Resistant Prostate Cancer: Treatment Patterns and Clinical Outcomes in Multicenter Community-Based US Oncology Practices.

BACKGROUND: Optimal sequencing of cabazitaxel (C) and abiraterone acetate (A) after docetaxel (D) for metastatic castration-resistant prostate cancer (mCRPC) is unclear. We assessed treatment patterns and outcomes in patients with mCRPC receiving different sequences of A or C, or both, after administration of D. METHODS: Retrospective analysis was conducted of US Oncology Network iKnowMed (iKM) electronic health record (EHR) data to assess patients with mCRPC who received treatment with D and were subsequently treated with C or A, or both, between April 2011 and May 2012. Patients received 2 or 3 drugs: DA, DC, DAC, or DCA. Overall survival (OS) and time to treatment failure (TTF) were analyzed by the Kaplan-Meier method from the start to the end of second-line therapy after administration of D (TTF1) and to the end of combined second- and third-line therapy (TTF2) for 3-drug sequences. Multivariable Cox proportional hazard models evaluated the impact of baseline clinical prognostic factors and treatment sequence on OS and TTF. RESULTS: Of 350 patients who were treated with D and subsequent therapies, 183 (52.3%) received DA, 54 (15.4%) received DC, 77 (22.0%) received DCA, and 36 (10.3%) received DAC. In a multivariable analysis, adjusted comparisons suggested that 3-drug sequences were associated with improved OS versus 2-drug sequences (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.092-0.476; P = .0002). There were no statistically significant differences in OS and TTF for DC versus DA, and OS was significantly greater for DCA versus DAC (HR, 0.13; 95% CI, 0.022-0.733; P = .0210). More cycles of C were administered in DCA than in DAC (median 6 vs. 4; t test P < .0001), whereas the duration of A treatment was similar. CONCLUSION: Administration of 3 agents in the DCA sequence was more optimal for treating mCRPC in this hypothesis-generating study.

First-Line and Sequential Use of Pazopanib Followed by Mammalian Target of Rapamycin Inhibitor Therapy Among Patients With Advanced Renal Cell Carcinoma in a US Community Oncology Setting.

BACKGROUND: Clinical trials have demonstrated that pazopanib prolongs progression-free survival (PFS), with an acceptable safety profile, for patients with advanced renal cell carcinoma (aRCC). The efficacy of second-line mammalian target of rapamycin (mTOR) inhibitors in pazopanib-treated patients has also been evaluated in clinical trials; however, few studies have evaluated first-line pazopanib or second-line mTOR inhibitors in real-world settings. The present study evaluated the outcomes of first-line pazopanib, and pazopanib followed by mTOR inhibitors, in a community oncology setting. PATIENTS AND METHODS: The present study was a retrospective analysis of eligible patients in US Oncology's iKnowMed electronic health records database who had been treated for aRCC from November 1, 2009 to August 31, 2012. The patients received first-line therapy with pazopanib (cohort 1), followed by second-line therapy with either everolimus or temsirolimus (cohort 2). The key outcomes included overall survival (OS), PFS, adverse events (AEs), treatment patterns, and healthcare resource use. RESULTS: The median OS in cohort 1 (n = 177) was 22 months, and the median PFS was 8.5 months. The most common AEs were fatigue (56%), diarrhea (52%), vomiting (44%), and nausea (40%). The median persistence was 151 days with pazopanib. The median OS in cohort 2 (n = 35) was 16 months; the median PFS was 5.7 months. The most common AEs were fatigue (51%) and nausea (34%). The median persistence was 93 days with everolimus and 49 days with temsirolimus. CONCLUSION: The outcomes for the patients treated with first-line pazopanib in the community setting were consistent with those reported by previous prospective and retrospective studies. Although the second-line cohort was small, the results of mTOR inhibitors after pazopanib were also consistent with those of previous observations.