Yttrium 90 Ibritumomab Tiuxetan Radioimmuno-therapy in Relapsed or Refractory Non-Hodgkin’s Lymphoma
Speaker: Thomas E. Witzig, MD, Associate Professor of Medicine, Cancer Center Research/Immunology Program, Mayo Clinic College of Medicine, and Hematology, Mayo Clinic, Rochester, Minnesota.
According to an analysis of long-term responders, yttrium 90 (Y) ibritumomab tiuxetan (Zevalin®, Biogen Idec) radio-immunotherapy produces durable long-term remissions, with time to progression (TTP) of disease being greater than 12 months, in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma (NHL).
Between 1996 and 1999, 211 patients with relapsed, refractory, or transformed indolent B-cell NHL were treated in four trials of Y ibritumomab tiuxetan. With a longer follow-up period, there was evidence of long-term durable responses.
To further characterize the patients with long-term responses, patients with time to progression of 12 months or longer were identified. By this defined criterion, durable responses were achieved in 38% of the patients (78 of 211 patients). The median age of these patients was 58 years; 44% were over age 60 and 55% were men. Seventy-six percent of this group had follicular lymphoma, and 41% had lymphoma-tous marrow involvement. A high percentage of these patients had undergone three or more previous therapies.
The complete response (CR) or complete response unconfirmed (CRu) rate in long-term responder (LTR) patients was 65%. In this group, the median duration of response was 29.3
months, and the time to progression was 31 months. Overall, the median duration of response in LTR patients (28.1 months) compared favorably with the duration of response to the last prior therapy for LTR patients (12 months).
At the time of this analysis, the median follow-up period was 45.6 months, with some responses lasting more than 75 months. The median duration of response in ongoing respon-ders to date was 48 months, and the time to progression of disease was 50.4 months.
Oblimersen Sodium Alone and with R-CHOP Mantle-Cell Lymphoma
Speaker: John P. Leonard, MD, Assistant Professor of Medicine, Weill Medical College of Cornell University, and Medical Director of the Center for Lymphoma and Myeloma and Assistant Attending Physician, New York Presbyterian Hospital, New York, New York.
Oblimersen sodium (Genasense™, Genta) is an antisense drug that blocks the production of Bcl-2, a cancer protein that contributes to the inherent resistance of cancer cells to anti-cancer treatment. It is well tolerated and has a modest but clear single-agent activity in patients with mantle-cell lymphoma, an aggressive form of NHL that is highly resistant to chemotherapy and generally considered incurable with conventional treatment. This drug can also be safely added to therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vin-cristine, and prednisone), bringing about responses in all patients treated to date.
A study was designed to evaluate the effects of escalating doses of oblimersen sodium used alone, without chemotherapy, in both patients with newly diagnosed disease and in previously treated patients receiving 3 mg/kg per day for seven days every 21 days, up to a maximum of six cycles.
Upon progression of disease, patients with newly diagnosed mantle-cell lymphoma who had not received chemotherapy were given oblimersen sodium plus R-CHOP for up to six cycles. Patients who had not responded to chemotherapy initially received the lowest dose of oblimersen sodium (3 mg/kg per day for six cycles) and were then given 4 mg/kg per day for seven days for subsequent cycles. A cohort, previously started at 4 mg/kg per day for cycle 1, was switched to 5 mg/kg per day for subsequent cycles.
A total of 47 patients were enrolled; 19 were new to chemotherapy and 28 had lymphoma that had relapsed from or had been refractory to earlier treatment. The primary endpoint was the overall response rate. Secondary endpoints included safety, CR rates, time to disease progression, and survival.
Across all treatment groups, of the 33 evaluable patients, 11 (33.3%) remained stable without disease progression during all six treatment cycles of oblimersen sodium alone. To date, of the 12 evaluable chemotherapy-naive patients with newly diagnosed mantle-cell lymphoma who completed oblimersen sodium plus R-CHOP therapy, four patients experienced CRs, three with CRs and one with a CRu; six patients had partial responses (PRs); and the remaining two patients had stable disease. In the 21 evaluable patients whose condition had relapsed or was refractory to earlier treatment, two patients had CRs (one a CR and one a CRu), one patient had a PR, nine patients had stable disease, and nine patients experienced disease progression. buy kamagra oral jelly
Oblimersen sodium did not appear to increase the toxicity of R-CHOP. Furthermore, in the previously treated patients who received monotherapy, escalating doses of this drug, from 3 mg/kg per day up to 5 mg/kg per day in subsequent cycles, appeared to be well tolerated.