Pharmacy & Therapeutics - February 2009 - (Page 98)

MEETING HIGHLIGHTS: American Society of Hematology tinued therapy for more than 39 months compared with those who discontinued treatment at 29.5 months. Similarly, median time to disease progression was longer for patients continuing therapy (for more than 16.2 months) than those stopping therapy (at 13.6 months). In an interview, Dr. San Miguel concluded, What we have observed is that the patients who discontinue treatment due to adverse events or who withdraw consent experience shorter time to progression and shorter overall survival than those who continue treatment. Physicians should manage side effects as soon as possible and [should] notify patients that the longer they undergo treatment, the longer their survival is likely to be prolonged. of treatment (P < 0.05). Reductions in cell-free hemoglobin and in nitric oxide consumption were also dramatically greater in the eculizumab group (P < 0.001 for both at 26 weeks). With PNH the most severe of all the hemolytic diseases, Dr. Hill concluded that eculizumab dramatically reduced hemolysis, hemoglobinemia, and nitric oxide consumption in patients with PNH while significantly reducing PAH, as measured via BNP and PAH-related symptoms. Ofatumumab (HuMax-CD20) in Refractory Chronic Lymphocytic Leukemia: Interim Analysis of a Pivotal Trial • Anders Osterborg, MD, Karolinska Hospital, Stockholm, Sweden For patients with chronic lymphocytic leukemia (CLL) refractory to both fludarabine (Fludara, Berlex) and alemtuzumab (Campath, Berlex) or who have bulky lymph nodes, the prognosis is poor. In a pilot study of CLL, the human CD20 monoclonal antibody ofatumumab (HuMAx-CD20, Genmab) showed promising activity, with an overall response rate of 50% in 27 patients receiving high-dose therapy. The study goal, Dr. Osterborg said, was to assess efficacy and safety in a CLL population with double-refractory (DR) disease (refractory to fludarabine and alemtuzumab) or with bulky fludarabine-refractory (BFR) disease (refractory to fludarabine and, because of bulky nodes greater than 5 cm, inappropriate for alemtuzumab). The open-label, single-arm, multicenter study was conducted in Europe and the U.S. The primary endpoint was objective response, according to 1996 National Cancer Institute–Working Group criteria. The median patient age was 63 years, with 73.5% male. These patients had received a median of 4.5 previous therapies. There was a high response rate for single-agent ofatumumab in this advanced-stage, CLL population with refractory disease. The overall response rates were 58% in the DR group and 47% in the BFR group. Ofatumumab was effective independent of earlier treatment with rituximab (Rituxan, Genentech), age, Rai stage at entry, and number of previous regimens. Responses also correlated with significantly improved survival outcomes: median progression-free survival rates were 5.7 months in the DR group and 5.9 months in the BFR group, and median overall survival rates were 13.7 months in the DR group and 15.4 months in the BFR group. Although median overall survival has not been reached by responders in either group, the rate exceeds median overall survival among non-responders (DR, 9.8 months, P = 0.0424; BFR, 10.2 months; P < 0.0001). Ofatumumab was well tolerated with no unexpected adverse events. The most common events in both groups were infections (affecting 25%) and neutropenia (affecting 10%). Nine patients died; six of the deaths occurred early and were not considered to be related to ofatumumab treatment. “The most important finding of this trial,” Dr. Osterborg said, “is that despite these patients being so heavily pretreated and having no evidence-based therapeutic possibilities left, we got new remissions in 50% to 60% of patients, and these were associated with prolonged survival.” continued on page 100 Eculizumab (Soliris) Reduces Pulmonary Hypertension in Paroxysmal Nocturnal Hemoglobinuria • Anita Hill, MD, Department of Hematology, Bradford Royal Infirmary, Bradford, U.K. In patients with paroxysmal nocturnal hemoglobinuria (PNH), the complement inhibitor eculizumab (Soliris, Alexion) reduces pulmonary arterial hypertension (PAH), brain natriuretic peptide (BNP) levels, and PAH-related symptoms. PAH affects 30% of patients with sickle-cell disease, and it is an independent risk factor for death in these patients. It is also a complication of other hemolytic anemias (defined as having N-terminal prohormone BNP levels of 160 pg/ml or higher, as in thalassemia, stomatocytosis, and spherocytosis). Hemolysis (red blood cell destruction) releases free hemoglobin, which leads through two pathways to nitric oxide consumption and, ultimately, to platelet aggregation and the thromboses of PAH and other vascular disorders. Symptoms of PNH include disabling fatigue, abdominal pain, shortness of breath, kidney dysfunction, thrombosis, and anemia; however, the most common clinical symptom, found in two-thirds of hemolytic PNH patients, is PAH-related dyspnea. Increased nitric oxide consumption far exceeds that noted in other hemolytic diseases. More than two-thirds of patients repor t shor tness of breath, moderate-to-severe dyspnea, and dyspnea-related distress. Eculizumab blocks hemolysis in patients with PNH and reduces these symptoms. Dr. Hill’s phase 3 randomized, placebo-controlled trial (TRIUMPH) assessed eculizumab’s impact on PAH in patients with PNH and evaluated levels of BNP. Elevated BNP indicates increased PAH and right ventricular dysfunction and is an independent marker of higher mortality risk. BNP levels were reduced to below160 pg/mL in more patients receiving eculizumab than placebo at 2 weeks, 14 weeks, and 26 weeks (35% vs. 6.1%; 29.7% vs. 7.4%; 28.9% vs. 12.5%, respectively; P < 0.001 for each). Similarly, BNP levels worsened to above 160 pg/mL in fewer patients receiving eculizumab at the same intervals. Median dyspnea scores improved from baseline to 26 weeks with eculizumab but not with placebo (P < 0.005). Median reductions in systemic systolic and diastolic blood pressure in the eculizumab patients were significantly greater than in the placebo group after four weeks 98 P&T® • February 2009 • Vol. 34 No. 2

Table of Contents Feed for the Digital Edition of Pharmacy & Therapeutics - February 2009

Pharmacy & Therapeutics - February 2009 Contents Editorial Medication Errors Prescription: Washington New Drugs/Drug News/New Medical Devices Drug Forecast Pushing an Expanded Role for Pharmacists Better Asthma Management with Advanced Technology Pharmaceutical Approval Update 58th Annual Meeting, American Society of Human Genetics, 2008 American Society of Hematology, 50th Annual Meeting and Exposition 2008 San Antonio Breast Cancer Symposium Stahl’s Essential Psychopharmacology, 3rd Edition Author Guidelines

Pharmacy & Therapeutics - February 2009

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