Pharmacy & Therapeutics - February 2009 - (Page 97)

MEETING HIGHLIGHTS: American Society of Hematology or, specifically, progression to the accelerated or blast phase. “This really demonstrates that achieving a major molecular response is very solid evidence of achieving a safe haven for CML patients,” Dr. Hughes said. He concluded, “Both molecular and cytogenetic evaluations should be used to guide treatment decisions.” thrombocytopenia (9%) occurred in the first two to three months and were seldom seen thereafter. Median duration of dose interruptions was nine days among the 40% of patients requiring them. Six patients withdrew from treatment. Compared with other experience in early chronic-phase CML, patients receiving nilotinib achieved MMRs sooner (Table 1). Dr. Cortes concluded that nilotinib produced rapid CCyRs more quickly than imatinib did. Molecular responses at 12 months were similar to those for high-dose imatinib. A high percentage of patients achieved undetectable transcript levels, and the toxicity profile was favorable. Nilotinib (Tasigna) versus Imatinib (Gleevec) For Newly Diagnosed, Previously Untreated Chronic Myelogenous Leukemia (Early Chronic Phase) • Jorge Cortes, MD, MD Anderson Cancer Center, Houston, Tex. Patients with early-chronic-phase, Philadelphia-positive (Ph+) CML achieved cytogenetic responses faster with nilotinib (Tasigna, Novartis) than with imatinib, and more nilotinibtreated patients achieved MMRs and undetectable transcript levels. Although imatinib induces CCyRs in 80% of patients with chronic-phase CML, molecular complete remissions are infrequent at standard doses. Earlier complete remissions are correlated with improved long-term outcomes. Derived from the imatinib molecule, nilotinib inhibits most imatinib-resistant bcr-abl kinase domain mutants except dasatinib (T3151, Sprycel, Bristol-Myers Squibb). Forty percent of chronic-phase CML patients who do not respond to imatinib achieve CCyRs with nilotinib. Dr. Cortes’ clinical trial included 53 patients (median age, 47 years); nine had previously received imatinib therapy. He noted that responses occurred early and improved over time. Best responses included complete hematological responses (CHRs) among all 47 patients not having CHRs at the start of treatment, CCyRs in 45 of 46 patients (97%) and MMRs in 25 of 47 patients (53%). Ten patients (21%) achieved complete molecular responses (CMRs). Although there were few molecular responses at three months (7%), by 12 months (the primary endpoint), 47% had achieved molecular responses, with CMRs achieved by 7%. Molecular responses increased over time. At 18 months, MMRs were reported in 65% of patients; among these, 30% experienced CMRs. At 12 months, the event-free survival rate was 89% and the overall survival rate was 100%. Adverse events with nilotinib were generally lower than with other therapies, Dr. Cortes said. Elevated liver enzyme levels were transient, and grade 3 and 4 neutropenia (11%) and Prolonged Therapy with Lenalidomide (Revlimid) plus Dexamethasone Extends Survival in Refractory Multiple Myeloma • Jesus F. San Miguel, Professor of Medicine, University Hospital of Salamanca, Salamanca, Spain Because extended treatment with lenalidomide (Revlimid, Celgene) and dexamethasone (Len/Dex) prolongs survival, every effort should be made to control adverse effects likely to cause withdrawal from treatment. In an analysis of data from two clinical trials of multiple myeloma (MM), Len/Dex, when compared with Dex alone, had demonstrated significant improvements in response rates, median time to disease progression, and overall survival in patients with relapsed or refractory MM. The objective of Dr. San Miguel’s clinical trial analysis was to determine whether maintaining treatment with Len/Dex after achieving best responses led to better overall survival and time to disease progression in MM patients compared with stopping treatment. The two trials (MM-009, MM-010) enrolled 353 patients treated with Len (25 mg/day on days 1 to 21 on an every-28-day cycle) and Dex (40 mg/day on days 1 to 4, 9 to 12, and 17 to 20, for four 28-day cycles and days 1 to 4 only from the fifth cycle onward). Among 321 responding patients, 107 (33%) had stable disease and 214 (67%) had a partial response or better. A landmark analysis assessed outcomes in those 223 patients who, after achieving best response, continued treatment for 10 months or less versus 98 patients who continued treatment for more than 10 months. In the two groups, the actual median duration of treatment was 6.6 months and 17.6 months. A second analysis evaluated the impact of early discontinuation resulting from adverse events or withdrawn consent on overall survival and time to disease progression in patients who achieved stable disease or better. In patients treated for more than 10 months, overall survival was significantly longer (more than 31.6 months) than in patients treated for 10 months or less (23.4 months, P < 0.0001). Furthermore, a significantly higher percentage of the patients treated for a longer time were alive at 24 months (93.8% vs. 48.4%; P < 0.0001). For the 214 patients who achieved partial responses or better, the median overall survival was longer with extended treatment (more than 31.6 months) compared with 26.9 months for those treated for less than 10 months (P < 0.0001). Median overall survival was also longer for patients who con- Table 1 Percentage of Patients Achieving Major Molecular Responses with Imatinib And Nilotinib Imatinib 400 mg (%) Parameter (N = 50) Imatinib 800 mg (%) (N = 205) Nilotinib 800 mg (%) (N = 53) 6 months 12 months 18 months 0 24 42 35 47 52 40 47 65 Vol. 34 No. 2 • February 2009 • P&T® 97

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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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