Citations

Purpose To delineate outcomes of malignant melanoma (MM) and Merkel cell carcinoma (MCC) in patients with chronic lymphocytic leukemia (CLL) or non-Hodgkin's lymphoma (NHL). Patients and Methods We identified patients with MM or MCC reported to the Surveillance, Epidemiology, and End Results program and analyzed the effects of history of CLL/NHL on overall (OS) and cause-specific survival after MM or MCC. Expected survival was derived from patients with MM or MCC without CLL/NHL. Results From 1990 to 2006, 212,245 patients with MM and 3,613 patients with MCC were identified, of whom 1,246 with MM and 90 with MCC had a prior diagnosis of CLL/NHL. Patients with MM and a history of CLL/NHL had worse-than-expected OS as measured by standardized mortality ratio (SMR; SMR for CLL, 2.6; 95% CI, 2.3 to 3.0; SMR for NHL, 2.3; 95% CI, 2.1 to 2.6). MM cause-specific survival was worse than expected for patients with a history of CLL (SMR, 2.8; 95% CI, 2.2 to 3.4) or NHL (SMR, 2.1; 95% CI, 1.7 to 2.6). Among patients with MCC, OS was worse than expected for those with a history of CLL (SMR, 3.1; 95% CI, 2.2 to 4.3) or NHL (SMR, 1.9; 95% CI, 1.3 to 2.8). MCC cause-specific survival was worse than expected for patients with a history of CLL (SMR, 3.8; 95% CI, 2.5 to 5.9), but no difference was observed for NHL (SMR, 0.9; 95% CI, 0.4 to 2.1). Conclusion Patients with CLL before diagnosis of MM or MCC have significantly worse OS and MM or MCC cause-specific survival than those without a history of CLL/NHL.

Purpose The trial objectives were to identify the maximum-tolerated dose (MTD) of first-line gemcitabine plus nab-paclitaxel in metastatic pancreatic adenocarcinoma and to provide efficacy and safety data. Additional objectives were to evaluate positron emission tomography (PET) scan response, secreted protein acidic and rich in cysteine (SPARC), and CA19-9 levels in relation to efficacy. Subsequent preclinical studies investigated the changes involving the pancreatic stroma and drug uptake. Patients and Methods Patients with previously untreated advanced pancreatic cancer were treated with 100, 125, or 150 mg/m 2 nab-paclitaxel followed by gemcitabine 1,000 mg/m 2 on days 1, 8, and 15 every 28 days. In the preclinical study, mice were implanted with human pancreatic cancers and treated with study agents. Results A total of 20, 44, and three patients received nab-paclitaxel at 100, 125, and 150 mg/m 2 , respectively. The MTD was 1,000 mg/m 2 of gemcitabine plus 125 mg/m 2 of nab-paclitaxel once a week for 3 weeks, every 28 days. Dose-limiting toxicities were sepsis and neutropenia. At the MTD, the response rate was 48%, with 12.2 median months of overall survival (OS) and 48% 1-year survival. Improved OS was observed in patients who had a complete metabolic response on [ 18 F]fluorodeoxyglucose PET. Decreases in CA19-9 levels were correlated with increased response rate, progression-free survival, and OS. SPARC in the stroma, but not in the tumor, was correlated with improved survival. In mice with human pancreatic cancer xenografts, nab-paclitaxel alone and in combination with gemcitabine depleted the desmoplastic stroma. The intratumoral concentration of gemcitabine was increased by 2.8-fold in mice receiving nab-paclitaxel plus gemcitabine versus those receiving gemcitabine alone. Conclusion The regimen of nab-paclitaxel plus gemcitabine has tolerable adverse effects with substantial antitumor activity, warranting phase III evaluation.

AbstractFree light chains (FLCs) are the most commonly detected paraproteins in chronic lymphocytic leukemia (CLL). We examined the types of FLC abnormalities and prognostic utility of the FLC assay compared with standard prognostic biomarkers in a prospective cohort of 339 patients with newly diagnosed CLL. Three types of FLC abnormalities were identified: monoclonal elevated FLC (elevated κ and/or λ with abnormal FLC ratio), polyclonal elevated FLC (elevated κ and/or λ with normal FLC ratio), and ratio-only FLC abnormality (normal range κ and λ with abnormal FLC ratio). One hundred sixty-five patients (49%) had a FLC abnormality with approximately equal distribution among monoclonal elevation, polyclonal elevation, and ratio-only abnormality. All FLC abnormalities were associated with poor time to first treatment: monoclonal FLC (hazard ratio [HR], 4.99; 95% confidence interval [CI], 2.94-8.48), polyclonal FLC (HR, 2.40; 95% CI, 1.24-4.64), ratio-only FLC (HR, 2.57; 95% CI, 1.40-4.69). Monoclonal FLC and polyclonal FLC were associated with poor overall survival compared with patients with normal FLC. Results remained significant after adjusting for Rai stage. The FLC assay is a simple, widely available clinical test with similar prognostic utility as routinely used prognostic biomarkers for CLL. Among persons with FLC abnormalities, the type of abnormality affects prognostic significance.