Treatment With Ibritumomab Tiuxetan Radioimmunotherapy in Patients With Rituximab-Refractory Follicular Non-Hodgkin’s Lymphoma

2002 ◽  
Vol 20 (15) ◽  
pp. 3262-3269 ◽  
Author(s):  
Thomas E. Witzig ◽  
Ian W. Flinn ◽  
Leo I. Gordon ◽  
Christos Emmanouilides ◽  
Myron S. Czuczman ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Objective Response ◽  
Hodgkin's Lymphoma ◽  
Outpatient Basis ◽  
Ibritumomab Tiuxetan ◽  
Non Hodgkin’S Lymphoma ◽  
Kaplan Meier ◽  
Non Hodgkin's Lymphoma ◽  
Indium 111

PURPOSE: Rituximab is commonly used as a single agent or in combination therapy for non-Hodgkin’s lymphoma (NHL). Ibritumomab tiuxetan radioimmunotherapy targets the same antigen as rituximab and has demonstrated efficacy in rituximab-naïve NHL. This study evaluated ibritumomab tiuxetan in the treatment of rituximab-refractory follicular NHL. PATIENTS AND METHODS: Eligible patients were refractory to rituximab; this was defined as no objective response to rituximab (375 mg/m2 weekly for 4 weeks) or time to progression (TTP) of ≤ 6 months. The ibritumomab tiuxetan treatment regimen consisted of pretreatment with rituximab (250 mg/m2 intravenously on days 1 and 8) to deplete peripheral blood B cells, then yttrium-90 ibritumomab tiuxetan (0.4 mCi/kg; maximum, 32 mCi) intravenously on day 8, administered on an outpatient basis. An imaging/dosimetry dose of indium-111 ibritumomab tiuxetan (5 mCi) was injected after rituximab (day 1) in 28 patients. RESULTS: Fifty-seven patients were treated. The median age was 54 years, 74% had tumors ≥ 5 cm, and all were extensively pretreated (median, four prior therapies; range, one to nine). The estimated radiation-absorbed doses to healthy organs were below the study-defined limit in all patients studied with dosimetry. The overall response rate for the 54 patients with follicular NHL was 74% (15% complete responses and 59% partial responses). The Kaplan-Meier–estimated TTP was 6.8 months (range, 1.1 to ≥ 25.9 months) for all patients and 8.7 months for responders. Adverse events were primarily hematologic; the incidence of grade 4 neutropenia, thrombocytopenia, and anemia was 35%, 9%, and 4%, respectively. CONCLUSION: Ibritumomab tiuxetan radioimmunotherapy is effective in rituximab-refractory patients. The only significant toxicity is hematologic.

A prospective study of a new combination chemotherapy regimen in patients older than 70 years with unfavorable non-Hodgkin's lymphoma.

1992 ◽  
Vol 10 (2) ◽  
pp. 228-236 ◽  
Author(s):  
U Tirelli ◽  
V Zagonel ◽  
D Errante ◽  
D Serraino ◽  
R Talamini ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Objective Response ◽  
Prospective Trial ◽  
Hodgkin's Lymphoma ◽  
New Combination ◽  
Low Grade ◽  
Outpatient Basis ◽  
Symptomatic Disease ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE A prospective trial with a new combination of etoposide, mitoxantrone, and prednimustine (VMP), specifically devised for elderly patients with non-Hodgkin's lymphoma (NHL), was undertaken. PATIENTS AND METHODS Between January 1987 and April 1990, 52 consecutive unselected patients older than 70 years (median age, 75.6 years) with stage I to IV intermediate- and high-grade NHL, or with stage III to IV low-grade malignancy with symptomatic disease received etoposide and prednimustine 80 mg/m2 orally for 5 days and mitoxantrone 8 to 10 mg/m2 day 1 intravenously (IV), every 21 days. Fourteen patients were previously treated. RESULTS Among the 48 assessable patients, the objective response rate was 81%; 46% of the patients achieved a complete response (CR). The overall toxicity seemed to be acceptable, with 15 (7%) episodes of grade 4 leukopenia and 41 (18%) episodes of grade 3, over a total of 226 administered cycles. The median survival was 12 months. The patients who obtained CR have a longer survival than those who did not (34 v 8 months; P less than .001). Fifty-eight percent of patients achieving CR were free from relapse at 24 months; up to 36 months from the start of therapy, 25% were free from relapse. As far as patients affected by diffuse histiocytic lymphoma, 66% of previously untreated patients obtained a CR, and 55% of them were still disease-free at 24 months from the start of therapy. CONCLUSION We conclude that VMP is effective, well tolerated, and feasible on an outpatient basis in an unselected, elderly population affected by unfavorable NHL.

Maximizing Therapeutic Benefit of Rituximab: Maintenance Therapy Versus Re-Treatment at Progression in Patients With Indolent Non-Hodgkin's Lymphoma—A Randomized Phase II Trial of the Minnie Pearl Cancer Research Network

2005 ◽  
Vol 23 (6) ◽  
pp. 1088-1095 ◽  
Author(s):  
John D. Hainsworth ◽  
Sharlene Litchy ◽  
Don W. Shaffer ◽  
Van L. Lackey ◽  
Manuel Grimaldi ◽  
...  
Keyword(s):  
Stable Disease ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Objective Response ◽  
Hodgkin's Lymphoma ◽  
Research Network ◽  
Phase Iii ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Maintenance Group

Purpose To compare the benefit of maintenance rituximab therapy versus rituximab re-treatment at progression in patients with previously treated indolent non-Hodgkin's lymphoma. Patients and Methods Between June 1998 and August 2002, 114 patients who had received previous chemotherapy for indolent non-Hodgkin's lymphoma were treated with a standard 4-week course of rituximab. Patients with objective response or stable disease were randomly assigned to receive either maintenance rituximab therapy (standard 4-week courses administered at 6-month intervals) or rituximab re-treatment at the time of lymphoma progression. The duration of rituximab benefit was measured from the date of first rituximab treatment until the date other treatment was required. Results Ninety (79%) of 114 patients had objective response or stable disease after initial rituximab treatment, and were randomly assigned to treatment. Progression-free survival was prolonged in the maintenance group (31.3 v 7.4 months; P = .007). Final overall and complete response rates were higher in the maintenance group. Duration of rituximab benefit was similar in the maintenance and re-treatment groups (31.3 v 27.4 months, respectively). More maintenance patients remain in continuous remission, and more are currently in complete remission. Both treatment approaches were well tolerated. Conclusion In patients who have objective response or stable disease with single-agent rituximab therapy, duration of rituximab benefit is substantially prolonged with either scheduled maintenance treatment or rituximab re-treatment at the time of progression. At present, the magnitude of benefit with either approach appears similar. However, additional follow-up of this trial is required, and completion of phase III randomized trials is necessary to definitively answer this question.

Lenalidomide Oral Monotherapy Produces Durable Responses in Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma

2009 ◽  
Vol 27 (32) ◽  
pp. 5404-5409 ◽  
Author(s):  
Thomas E. Witzig ◽  
Peter H. Wiernik ◽  
Timothy Moore ◽  
Craig Reeder ◽  
Craig Cole ◽  
...  
Keyword(s):  
Adverse Events ◽  
Hodgkin’S Lymphoma ◽  
Single Agent ◽  
Objective Response ◽  
Progression Free Survival ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Wide Range

Purpose Lenalidomide is a novel immunomodulatory agent with antiproliferative activities. Given its efficacy in a wide range of hematologic malignancies, we conducted a phase II trial (NHL-001) of single-agent lenalidomide in indolent non-Hodgkin's lymphoma (NHL). Patients and Methods Patients with relapsed/refractory indolent NHL were eligible, with no limit on the number of previous therapies. Oral lenalidomide 25 mg was self-administered once daily on days 1 to 21 of every 28-day cycle for up to 52 weeks as tolerated, or until disease progression. The primary end point was objective response rate (ORR), with secondary end points of duration of response (DR), progression-free survival (PFS), and safety. Results Forty-three enrolled patients were assessable for response and safety. Patients received a median of three prior systemic therapies (range, 1 to 17) and half were refractory to last therapy. ORR was 23% (10 of 43), including a 7% complete response (CR) or unconfirmed CR rate. Twenty-seven percent (six of 22) of patients with follicular lymphoma grade 1 or 2, and 22% (four of 18) with small lymphocytic lymphoma responded to therapy. Median DR was not reached, but was longer than 16.5 months with seven of 10 responses ongoing at 15 to 28 months. Median PFS for the whole group was 4.4 months (95% CI, 2.5 to 10.4 months). Adverse events were predictable and manageable; the most common grade 3 or 4 adverse events were neutropenia (30% and 16%, respectively) and thrombocytopenia (14% and 5%, respectively). Conclusion Oral lenalidomide monotherapy produces durable responses with manageable adverse events in patients with relapsed/refractory indolent NHL, warranting further investigation of treatment for indolent NHL.

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

CHOP is the standard regimen in patients > or = 70 years of age with intermediate-grade and high-grade non-Hodgkin's lymphoma: results of a randomized study of the European Organization for Research and Treatment of Cancer Lymphoma Cooperative Study Group.

1998 ◽  
Vol 16 (1) ◽  
pp. 27-34 ◽  
Author(s):  
U Tirelli ◽  
D Errante ◽  
M Van Glabbeke ◽  
I Teodorovic ◽  
J C Kluin-Nelemans ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Randomized Study ◽  
Objective Response ◽  
Stage Ii ◽  
Hodgkin's Lymphoma ◽  
High Grade ◽  
Standard Regimen ◽  
European Organization ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE We report the results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Group, which compared a chemotherapy regimen specifically devised for elderly patients, ie, etoposide, mitoxantrone, and prednimustine (VMP), versus the standard regimen of cyclophosphamide, doxorobucin, vincristine, and prednisone (CHOP) in patients older than 70 years of age with intermediate- and high-grade non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Patients older than 70 years of age with stage II, III, or IV intermediate- and high-grade NHL, with an Eastern Cooperative Oncology Group (ECOG) performance status less than 4 and acceptable cardiac, renal, and liver function were randomized to receive six courses of VMP or six courses of CHOP. Between February 1989 and June 1994, 130 patients aged 70 to 93 years (median, 75) were enrolled and 120 were assessable for response, 60 patients in each arm. RESULTS Overall objective response rates were 50% and 77% in VMP- and CHOP-treated patients, respectively (P = .01), while complete response (CR) rates were borderline significant (27% v 45%; P = .06). At 2 years, the progression-free survival (PFS) rate was 25% with VMP versus 55% with CHOP (P = .002) and the overall survival (OS) rate was 30% with VMP versus 65% with CHOP (P = .004). Statistically significant more alopecia and neurologic and gastrointestinal toxicities were reported with CHOP. CONCLUSION CHOP is the standard regimen for patients > or = 70 years of age with stage II to IV intermediate- and high-grade NHL.

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

Infusional cyclophosphamide, doxorubicin, and etoposide in relapsed and resistant non-Hodgkin's lymphoma: evidence for a schedule-dependent effect favoring infusional administration of chemotherapy.

1993 ◽  
Vol 11 (6) ◽  
pp. 1071-1079 ◽  
Author(s):  
J A Sparano ◽  
P H Wiernik ◽  
A Leaf ◽  
J P Dutcher
Keyword(s):  
Confidence Interval ◽  
Hodgkin’S Lymphoma ◽  
Objective Response ◽  
Cytotoxic Agents ◽  
Hodgkin's Lymphoma ◽  
Dependent Effect ◽  
Prognostic Features ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

PURPOSE This study attempted to determine the efficacy of cyclophosphamide (C), doxorubicin (D), and etoposide (E) administered as a continuous intravenous (IV) infusion (infusional CDE) over 4 days in patients with relapsed or resistant non-Hodgkin's lymphoma (rNHL) and in patients with previously untreated (uNHL) who had poor prognostic features. PATIENTS AND METHODS Fifty-eight patients with rNHL and 10 patients with uNHL received infusional CDE every 28 or more days; all but one had intermediate- to high-grade histology. The cumulative doses of C, D, and E administered per treatment cycle were 750 mg/m2, 50 mg/m2, and 240 mg/m2, respectively. In the rNHL group, all patients had previously received C, most (81%) had received D, and a minority (16%) had received E. RESULTS Objective response occurred in 30 patients with rNHL (52%; 95% confidence interval, 39% to 65%); 10 patients had a complete response (CR) (17%; 95% confidence interval, 7% to 27%). Eleven patients (19%) remain progression-free (median follow-up, 22 months; range, 10+ to 38+), and six patients (10%) are disease-free (median follow-up, 25 months; range, 10+ to 38+). Among 10 patients with uNHL, eight (80%) had a CR, and none have relapsed (median follow-up, 11 months; range, 9+ to 24+). Toxicity was primarily hematologic. Two treatment-related deaths (3%) occurred, both attributable to infection in the relapsed or resistant group. CONCLUSION Infusional CDE produced a CR in substantial proportion of patients who had previously been exposed to at least two of the agents administered as an IV bolus, suggesting a schedule-dependent effect in favor of the infusional administration of certain cytotoxic agents in patients with lymphoid neoplasms. In addition, infusional CDE was effective and tolerable in patients with poor-prognosis NHL when used as initial therapy, and merits further study in that setting.

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