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.

Pegylated liposomal doxorubicin as single-agent treatment of low-grade non-Hodgkin's lymphoma: a phase II multicenter study.

The purpose of this study was to determine the objective response rate, median duration of response, time to disease progression, and survival time and to evaluate the safety of pegylated liposomal doxorubicin in previously treated patients with low-grade non-Hodgkin's lymphoma. Thirty-two patients with low-grade non-Hodgkin's lymphoma were treated and analyzed. Pegylated liposomal doxorubicin 30 mg/m2 was administered intravenously as a single dose on day 1 of each 3-week cycle. Patients had an Eastern Cooperative Oncology Group performance status of 0-1 and had stage II-IV disease. The median baseline left ventricular ejection fraction was 60%, and the median age was 68 years. In 29 evaluable patients, there were 3 (10%) complete responses, 6 (21%) partial responses, 11 (38%) patients with stable disease, and 9 (31%) with progressive disease. The median number of cycles was 4 (range, 1-22 cycles). The median duration of response (complete response plus partial response) was 11.0 months (range, 2.3-37.0 months). The estimated median time to progression was 5.6 months (range, 1.1-40.5 months) and the estimated median survival was 29.6 months (range, 3.9-41.6 months). Treatment-related toxicities grade = 3 included neutropenia (25%) and palmoplantar erythrodysesthesia (9%). Only 1 clinically significant cardiac toxicity was observed. There were 17 deaths; none were treatment related. Single-agent pegylated liposomal doxorubicin 30 mg/m2 every 3 weeks, is associated with antitumor activity in the treatment of low-grade non-Hodgkin's lymphoma, as shown by an objective response of 31%, and produced no significant cardiac or hematologic toxicity. Based on these results, pegylated liposomal doxorubicin should be further evaluated in combination with other agents in low-grade non-Hodgkin's lymphoma.

Results of a phase II multicenter trial of pentostatin and rituximab in patients with low grade B-cell non-Hodgkin's lymphoma: an effective and minimally toxic regimen.

This study explored the efficacy and toxicity of the combination of pentostatin and rituximab, effective single agents in low-grade non-Hodgkin's lymphoma (NHL). Sixty patients with previously treated low-grade NHL were enrolled. Except for day 1, both drugs were administered weekly for 4 weeks, with week 5 off. During week 1 (day 1) only rituximab was given; subsequent weekly treatments included both drugs. Patients received a minimum of 2 five-week cycles in order to be evaluable for efficacy. Responses were evaluated on week 5 of cycle 2. If partial response (PR) or stable disease (SD) responses were noted, 2 additional cycles were administered. Final evaluations were done on week 5 of cycle 4. Of 60 patients, 58.3% had an Eastern Cooperative Oncology Group performance status (PS) of 0, and 41.7% had PS of 1; 31.7% and 51.7% had stage III or stage IV disease, respectively. Histology included follicular center, follicular, grade I (45%), II (21.7%), III (1.7%), and small lymphocytic (31.7%). Seventeen patients had prior chemotherapy, but no patients had received prior pentostatin or rituximab. Median age was 60.3 years (range, 32.5-84.7 years). Among 57 evaluable patients, 77% responded (22.3% complete response [CR], 3.5% unconfirmed CR, 35.1% PR, and 10.5% unconfirmed PR); 19.3% had SD, and 8.8% progressive disease (PD). Response rate among previously untreated patients was 83% versus 63% in previously treated patients. Median duration of response was 11 months (range, 2.3-22.2 months); median time to progression was 15 months (range, < 1-25 months). Neutropenia was the only adverse event experienced by >/= 10% of patients. Six deaths were caused by PD, and one death each was caused by acute respiratory distress, possibly related respiratory failure, and cardiac toxicity. These results suggest the combination of pentostatin/rituximab is well tolerated and active in low-grade lymphoma.