Randomized Controlled Trial of Yttrium-90–Labeled Ibritumomab Tiuxetan Radioimmunotherapy Versus Rituximab Immunotherapy for Patients With Relapsed or Refractory Low-Grade, Follicular, or Transformed B-Cell Non-Hodgkin’s Lymphoma

2002 ◽  
Vol 20 (10) ◽  
pp. 2453-2463 ◽  
Author(s):  
Thomas E. Witzig ◽  
Leo I. Gordon ◽  
Fernando Cabanillas ◽  
Myron S. Czuczman ◽  
Christos Emmanouilides ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Group Versus ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Control Group ◽  
Low Grade ◽  
Ibritumomab Tiuxetan ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Yttrium 90

PURPOSE: Radioimmunotherapy combines biologic and radiolytic mechanisms to target and destroy tumor cells, thus offering a needed therapeutic alternative for refractory non-Hodgkin’s lymphoma (NHL) patients. This phase III randomized study compares the novel radioimmunotherapy yttrium-90 (90Y) ibritumomab tiuxetan with a control immunotherapy, rituximab, in 143 patients with relapsed or refractory low-grade, follicular, or transformed CD20+ transformed NHL. PATIENTS AND METHODS: Patients received either a single intravenous (IV) dose of 90Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m2 IV weekly for four doses (n = 70). The radioimmunotherapy group was pretreated with two rituximab doses (250 mg/m2) to improve biodistribution and one dose of indium-111 ibritumomab tiuxetan for imaging and dosimetry. The primary end point, overall response rate (ORR), was assessed by an independent, blinded, lymphoma expert panel. RESULTS: ORR was 80% for the 90Y ibritumomab tiuxetan group versus 56% for the rituximab group (P = .002). Complete response (CR) rates were 30% and 16% in the 90Y ibritumomab tiuxetan and rituximab groups, respectively (P = .04). An additional 4% achieved an unconfirmed CR in each group. Kaplan-Meier estimated median duration of response was 14.2 months in the 90Y ibritumomab tiuxetan group versus 12.1 months in the control group (P = .6), and time to progression was 11.2 versus 10.1 months (P = .173) in all patients. Durable responses of ≥ 6 months were 64% versus 47% (P = .030). Reversible myelosuppression was the primary toxicity noted with 90Y ibritumomab tiuxetan. CONCLUSION: Radioimmunotherapy with 90Y ibritumomab tiuxetan is well tolerated and produces statistically and clinically significant higher ORR and CR compared with rituximab alone.

Yttrium 90 ibritumomab tiuxetan radioimmunotherapy for relapsed or refractory low-grade non-Hodgkin's lymphoma

2002 ◽  
Vol 29 (1) ◽  
pp. 87-92 ◽  
Author(s):  
Leo I Gordon ◽  
Thomas E Witzig ◽  
Greg A Wiseman ◽  
Ian W Flinn ◽  
Stewart S Spies ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Low Grade ◽  
Ibritumomab Tiuxetan ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Yttrium 90

Safety of Yttrium-90 Ibritumomab Tiuxetan Radioimmunotherapy for Relapsed Low-Grade, Follicular, or Transformed Non-Hodgkin’s Lymphoma

2003 ◽  
Vol 21 (7) ◽  
pp. 1263-1270 ◽  
Author(s):  
Thomas E. Witzig ◽  
Christine A. White ◽  
Leo I. Gordon ◽  
Gregory A. Wiseman ◽  
Christos Emmanouilides ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Bone Marrow Involvement ◽  
Myelogenous Leukemia ◽  
Hodgkin's Lymphoma ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Ibritumomab Tiuxetan ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Yttrium 90

Purpose: Radioimmunotherapy (RIT) with yttrium-90 (90Y)-labeled anti-CD20 antibody (90Y ibritumomab tiuxetan; Zevalin, IDEC Pharmaceuticals Corporation, San Diego, CA) has a high rate of tumor response in patients with relapsed or refractory, low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma (NHL). This study presents the safety data from 349 patients in five studies of outpatient treatment with 90Y ibritumomab tiuxetan. Patients and Methods: Patients received rituximab 250 mg/m2 on days 1 and 8, and either 0.4 mCi/kg (15 MBq/kg) or 0.3 mCi/kg (11 MBq/kg) of 90Y ibritumomab tiuxetan on day 8 (maximum dose, 32 mCi). Patients were observed for up to 4 years after therapy or until progressive disease. Results: Infusion-related toxicities were typically grade 1 or 2 and were associated with rituximab. No significant organ toxicity was noted. Toxicity was primarily hematologic, with nadir counts occurring at 7 to 9 weeks and lasting approximately 1 to 4 weeks depending on the method of calculation. After the 0.4-mCi/kg dose, grade 4 neutropenia, thrombocytopenia, and anemia occurred in 30%, 10%, and 3% of patients, respectively, and after the 0.3-mCi/kg dose, these grade 4 toxicities occurred in 35%, 14%, and 8% of patients, respectively. The risk of hematologic toxicity increased with degree of baseline bone marrow involvement with NHL. Seven percent of patients were hospitalized with infection (3% with neutropenia) and 2% had grade 3 or 4 bleeding events. Myelodysplasia or acute myelogenous leukemia was reported in five patients (1%) 8 to 34 months after treatment. Conclusion: Single-dose 90Y ibritumomab tiuxetan RIT has an acceptable safety profile in relapsed NHL patients with less than 25% lymphoma marrow involvement, adequate marrow reserve, platelets greater than 100,000 cells/μL, and neutrophils greater than 1,500 cells/μL.

Retreatment with yttrium-90 ibritumomab tiuxetan in patients with B-cell non-Hodgkin's lymphoma

2007 ◽  
Vol 48 (9) ◽  
pp. 1736-1744 ◽  
Author(s):  
Jatin Shah ◽  
Wenquan Wang ◽  
V. Douglas Harrough ◽  
Wayne Saville ◽  
Ruby Meredith ◽  
...  
Keyword(s):  
B Cell ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Ibritumomab Tiuxetan ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Yttrium 90

Rituximab Anti-CD20 Monoclonal Antibody Therapy in Non-Hodgkin’s Lymphoma: Safety and Efficacy of Re-Treatment

2000 ◽  
Vol 18 (17) ◽  
pp. 3135-3143 ◽  
Author(s):  
Thomas A. Davis ◽  
Antonio J. Grillo-López ◽  
Christine A. White ◽  
Peter McLaughlin ◽  
Myron S. Czuczman ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Low Grade ◽  
Phase Iii Trial ◽  
Safety And Efficacy ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Anti Cd20

PURPOSE: This phase II trial investigated the safety and efficacy of re-treatment with rituximab, a chimeric anti-CD20 monoclonal antibody, in patients with low-grade or follicular non-Hodgkin’s lymphoma who relapsed after a response to rituximab therapy. PATIENTS AND METHODS: Fifty-eight patients were enrolled onto this study, and two were re-treated within the study. Patients received an intravenous infusion of 375 mg/m2 of rituximab weekly for 4 weeks. All patients had at least two prior therapies and had received at least one prior course of rituximab, with a median interval of 14.5 months between rituximab courses. RESULTS: Most adverse experiences (AEs) were transient grade 1 or 2 events occurring during the treatment period. Clinically significant myelosuppression was not observed; hematologic toxicity was generally mild and reversible. No patient developed human antichimeric antibodies after treatment. The type, frequency, and severity of AEs in this study were not apparently different from those reported in the phase III trial of rituximab. The overall response rate in 57 assessable patients was 40% (11% complete response and 30% partial responses). Median time to progression (TTP) in responders and median duration of response (DR) have not been reached, but Kaplan-Meier estimated medians are 17.8 months (range, 5.4+ to 26.6 months) and 16.3 months (range, 3.7+ to 25.1 months), respectively. These estimated medians are longer than the medians achieved in the patients’ prior course of rituximab (TTP and DR of 12.4 and 9.8 months, respectively, P > .1) and in a previously reported phase III trial (TTP in responders and DR of 13.2 and 11.6 months, respectively). Responses are ongoing in seven of 23 responders. CONCLUSION: In this re-treatment population, safety and efficacy were not apparently different from those after initial rituximab exposure.

Phase III Intergroup Study of Fludarabine Phosphate Compared With Cyclophosphamide, Vincristine, and Prednisone Chemotherapy in Newly Diagnosed Patients With Stage III and IV Low-Grade Malignant Non-Hodgkin's Lymphoma

2006 ◽  
Vol 24 (10) ◽  
pp. 1590-1596 ◽  
Author(s):  
Anton Hagenbeek ◽  
Houchingue Eghbali ◽  
Silvio Monfardini ◽  
Umberto Vitolo ◽  
Peter J. Hoskin ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
Low Grade ◽  
Newly Diagnosed ◽  
Fludarabine Phosphate ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

Purpose To compare the efficacy and safety of fludarabine phosphate with cyclophosphamide, vincristine, and prednisone (CVP) in 381 previously untreated, advanced-stage, low-grade (lg) non-Hodgkin's lymphoma (NHL) patients in a phase III, multicenter study. Patients and Methods Between 1993 and 1997, patients were randomly assigned to treatment with either fludarabine (25 mg/m2 intravenously [IV] daily for 5 days every 4 weeks) or CVP (cyclophosphamide 750 mg/m2 IV on day 1; vincristine, 1.4 mg/m2 IV on day 1; and prednisone, 40 mg/m2 orally on days 1 through 5 every 4 weeks). Results Overall response (OR) rates were significantly improved in the fludarabine arm versus the CVP arm, both for the intent-to-treat (ITT) population and assessable patients (P < .001). Complete response (CR) rates in the ITT population were also higher after fludarabine treatment. The CR rate was 38.6% for fludarabine compared with 15.0% for CVP. There were no statistically significant differences in time to progression (TTP), time to treatment failure (TTF), and overall survival (OS) between treatment groups. WHO grades 3 and 4 hematologic adverse events were more common in the fludarabine arm. However, concerning the higher incidence of granulocytopenia, this did not translate to more infections in fludarabine-treated patients. Conclusion Newly diagnosed lgNHL patients who received fludarabine achieved higher OR and CR rates compared with CVP-treated patients. No differences in TTP, TTF, and OS were noted. Fludarabine is a highly active single agent in lgNHL. Combination therapies incorporating fludarabine are now being further evaluated as first-line therapy in follicular NHL.

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