42nd Annual Meeting: High-Risk Cytogenetic Abnormalities Respond to Alemtuzumab in Patients with B-Cell Chronic Lymphocytic Leukemia

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High-Risk Cytogenetic Abnormalities Respond to Alemtuzumab in Patients with B-Cell Chronic Lymphocytic Leukemia

Presenter: Anna Dmoszynska, MD, Professor, Department of Hematology, Medical University of Lublin, Lublin, Poland

A cytogenetic profile of the patients participating in a large-scale clinical trial comparing alemtuzumab (Campath, Berlex/ Genzyme) with chlorambucil (Leukeran, GlaxoSmithKline) in previously untreated patients with progressive B-cell chronic lymphocytic leukemia (B-CLL) demonstrated statistically superior overall response rates and complete response rates to alemtuzumab in patients with certain poor prognostic cyto-genetic abnormalities compared with patients treated with chlorambucil. This drug looks promising as a novel, more effective therapeutic option for patients with poor-risk B-CLL.

A total of 297 patients with previously untreated Rai stage I-V B-CLL were enrolled in a phase 3, open-label, randomized comparative trial. The patients were assigned to receive standard dosing regimens of alemtuzumab (n = 149) or chlorambucil (n = 148). Patients received intravenous (IV) alemtuzumab 30 mg three times weekly for a maximum of 12 weeks or oral chlorambucil 40 mg/m² once every 28 days for a maximum of 12 cycles. cheap cialis canadian pharmacy

As part of the overall study, a cytogenetic assessment was conducted before the start of the protocol-specified therapy. Chromosome aberrations were detected by fluorescence in situ hybridization (FISH) via specific DNA probes, including deletions (del) 6q21, 6q telomere, 11q 22-23, 13q 14-14.3, and 17p13, as well as trisomy bands of 8q24 and 12p11.1-q11.1.

Statistically significant higher overall and complete response rates to alemtuzumab were observed in patients with a 13q deletion (a common genetic defect in patients with B-CLL) and in overall response rates of patients with an 11q deletion (a cytogenetic abnormality typically associated with poor prognosis).

In patients with a 17p deletion, another marker of poor prognosis, the overall response rates were three times higher with alemtuzumab (64%) than with chlorambucil (20%). This trend, however, did not reach statistical significance because the sample size was small.

Finally, patients with a normal cytogenetic profile had statistically significant superior complete response rates with alemtuzumab (24% of 34 patients) compared with chlorambucil (0% of 31 patients).

Analyses of progression-free survival, overall survival, and the relationship to prognostic factors are ongoing. Because patients with poor-risk prognostic cytogenetic abnormalities have low response rates and short survival rates when treated with conventional chemotherapy, further studies using alem-tuzumab in these individuals are warranted. buy antibiotics without prescription

Dasatinib Active in Patients with Resistant Chronic Myelogenous Leukemia

Speaker: Zeev Estoy, MD, Professor, Leukemia and Experimental Therapeutics, Leukemia/Bioimmunotherapy Center, University of Texas M.D. Anderson Cancer Center, Houston, Texas

Dasatinib (Sprycel, Bristol-Myers Squibb), a novel, oral dual Src-Abl kinase inhibitor, shows activity in patients with Philadelphia chromosome-positive chronic myelogenous leukemia (Ph + CML) whose condition is resistant to two No-vartis therapies: imatinib (Gleevec) and the investigational agent AMN 107. Dasatinib proved to be 300-fold more potent than imatinib (the standard second-line treatment for refractory CML) and 20-fold more potent than AMN 107 (a potent oral tyrosine kinase inhibitor).

A study was conducted to report the experience with dasatinib in patients after treatment failure with AMN 107. Initially, all patients in the ongoing dasatinib studies at the M.D. Anderson Cancer Center were reviewed for previous therapy and their responses to AMN 107 and outcomes with imatinib. Sixteen patients with Ph + CML, all of whom had shown previous hematological resistance to imatinib, followed by treatment failure with AMN 107, received dasatinib 70 mg orally twice daily (10 patients), 140 mg orally in a single daily dose (five patients), or 120 mg orally twice daily (one patient).

In this group of patients, the CML phase was classified as “chronic” in two patients, “accelerated” in six patients, and “blastic” in six patients; a second, or repeated, CML phase was classified as “chronic/accelerated” in two patients. The median follow-up period for dasatinib was three months (range, from less than one month to nine months).

Responses were reported in five of seven patients with Abl mutations, including four of four patients with loop mutations and one of two patients with other mutations. Two patients with Abl mutations in gene T3151 had resistant disease.
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For more information on Sprycel, see this month’s Pharmaceutical Approval Update: Oncology column on page 542.

Ibritumomab Tiuxetan plus High-Dose Chemotherapy Before Stem-Cell Transplantation Improves Outcomes in Non-Hodgkin’s Lymphoma

Speaker: Avichai Shimoni, MD, Specialist in Internal Medicine, Hematology and Bone Marrow Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel

Yttrium ibritumomab tiuxetan (Y IT) (Zevalin, Scher-ing/Biogen Idec), when combined with high-dose chemotherapy in a conditioning regimen given before autologous stem-cell transplantation (SCT), may reduce the risk of relapse following the procedure and may improve the poor outcome of patients with refractory non-Hodgkin’s lymphoma (NHL) who undergo SCT with standard conditioning regimens.

Although high-dose chemotherapy and autologous SCT have an established therapeutic role in patients with a first chemosensitive relapse of aggressive NHL, autologous SCT has only limited success when administered in a refractory or progressive stage of the disease in heavily pretreated individuals or in patients who experienced multiple relapses.

Twenty patients with refractory NHL and active lymphoma, as shown on positron emission tomography and computed tomography (PET and CT) scans, were given a conditioning regimen of rituximab (Rituxan, Biogen Idec/Genentech). The patients then received Y IT 0.4 mCi/kg, which was administered on “day minus 14″ prior to SCT (the 14th day before the procedure). A high-dose chemotherapy regimen of BEAM— carmustine (BiCNU), etoposide (Etoposide, Mylan), cytara-bine (DepoCyt, Enzon), and melphalan (Alkeran, Celgene)— was started on “day minus 6.” Autologous SCT was performed on day zero (0).

Of the 20 patients enrolled in the study, 18 were evaluable for their responses. Of these 18 individuals, 10 achieved complete responses and eight had partial responses. Four of these eight patients later had complete responses with additional external irradiation to residual disease. Five patients relapsed after SCT, with a one-year cumulative incidence of relapse of 26%. This is a relatively low relapse rate in patients with refractory disease. viagra soft

With a median follow-up period of 12 months, 13 patients were alive and seven died, and the estimated one-year overall survival rate was 59%. The projected one-year progression-free survival rate was 53%. This compared with an expected progression-free survival rate of less than 20% with standard transplantation in this high-risk population.

Concerning toxicity, no early infusion reactions occurred. Two patients died of multi-organ toxicities early after transplantation and before engraftment. The treatment-related non-relapse mortality at day 100, therefore, was 10%. Such rates of non-relapse mortality are expected in heavily pre-treated patients with refractory NHL. No additional toxicity was related to Y IT.