Rituximab in relapsed lymphocyte-predominant Hodgkin lymphoma: long-term results of a phase 2 trial by the German Hodgkin Lymphoma Study Group (GHSG).

Because nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) express CD20, rituximab may be used as a nonmutagenic treatment option to avoid late toxicities in this rather indolent entity. Between 1999 and 2004, the German Hodgkin Study Group (GHSG) investigated the activity of rituximab (375 mg/m(2) in 4 doses) in a phase 2 trial in 21 relapsed or refractory NLPHL patients. The initial diagnosis of NLPHL was confirmed in 15 of the 21 enrolled patients by reference pathology. The remaining cases were reclassified as Hodgkin lymphoma transformed to T-cell rich B-cell lymphoma (TCRBCL; n = 2) or CD20(+) classical Hodgkin lymphoma (cHL; n = 4). In NLPHL patients the overall response rate was 94%, including 8 complete remission (CR) and 6 partial remission (PR). With a median follow-up of 63 months (range, 3-84), the median time to progression was 33 months, with the median overall survival (OS) not reached. Thus, rituximab is highly effective in relapsed and refractory NLPHL. This study is registered at http://www.klinisches-studienzentrum.de/trial/285.

Sensitivity analysis of cost factors for various therapy options in the treatment of follicular lymphoma.

BACKGROUND: In Germany, patients with relapsed follicular non-Hodgkin's lymphoma do not all receive the same treatment. In this study, 3 therapy regimens were analyzed which were considered to be similar. With the goal of determining the treatment option with the lowest direct costs whilst maintaining the same degree of effectiveness, a cost analysis model was established and applied by way of example to the existing illness constellation. METHODS: The German doctors' fee scale (Einheitlicher Bewertungsmassstab, EBM) valid until 2005 served as the basis for the calculation of medical services within the scope of the present statutory health insurance guidelines. A virtual standard patient was constructed for the cost model and treated with the different therapy regimens. The incidences of individual adverse events described in literature served as the basis for the characterization of the average toxicity of the respective treatment methods. RESULT: The overall costs result from the sum of the treatment costs and the toxicity-related costs. The effect of additional interventions on the overall cost was also examined. CONCLUSION: Whereas the accompanying documentation of costs in clinical studies is organizationally complex and very tedious, the model applied here offers a reliable method of quantifying the costs of the different therapy regimens. It permits the comparison of different treatment alternatives, and it enables, by means of a cost variance analysis, the identification of cost drivers and less expensive measures within a therapy method.

Current treatment strategies for patients with Hodgkin's lymphoma and HIV infection.

Hodgkin's lymphoma is the most common non-AIDS-defining tumor diagnosed in HIV-infected patients. Although the introduction of highly active antiretroviral therapy (HAART) led to a decreased incidence of several malignancies among HIV-infected patients, the incidence of HIV-associated Hodgkin's lymphoma (HIV-HL) has been persistent in recent years. Its unusually aggressive tumor behavior includes a higher frequency of unfavorable histologic subtypes, high stage and extranodal involvement by the time of presentation and poor therapeutic outcome, in comparison with Hodgkin's lymphoma outside the HIV setting. Treatment of HIV-HL is challenging considering the underlying immunodeficiency caused by HIV itself and may increase the risk of opportunistic infections by inducing further immunosuppression. To address this delicate vulnerability of the HIV-infected host, tailored regimens, which are less aggressive than standard regimens for HIV-negative hosts, have been applied to achieve tumor control. The introduction of HAART has opened a new perspective in the treatment of HIV-associated malignancies. The improved control of HIV infection and the subsequently improved survival rates of HIV-infected patients has changed the goal from tumor control to cure and new treatment approaches with more potent regimens need to be evaluated to improve survival and quality of life in HIV-HL.

Treatment of relapsed CD20+ Hodgkin lymphoma with the monoclonal antibody rituximab is effective and well tolerated: results of a phase 2 trial of the German Hodgkin Lymphoma Study Group.

This phase 2 trial was performed to evaluate the safety and efficacy of the chimeric monoclonal anti-CD20 antibody rituximab in patients with relapsed lymphocyte-predominant Hodgkin lymphoma or other CD20(+) subtypes of Hodgkin disease (HD). Eligibility criteria required expression of the CD20 antigen on more than 30% of malignant cells. Fourteen patients were treated with 4 weekly intravenous infusions of rituximab (375 mg/m(2)). All patients had at least one prior chemotherapy (median, 2). The median time from first diagnosis was 9 years. Adverse events, such as rhinitis, fever, chills, and nausea, were usually transient and of mild to moderate grade, allowing outpatient treatment in most cases. All patients completed treatment and were eligible for a response. The overall response in 14 assessable patients was 86%, with 8 complete remissions and 4 partial remissions, and 2 patients with progressive disease. At a median follow-up of 12 months, 9 of 12 responders were in remission. The median duration of response has not been reached yet (20+ months). We conclude that rituximab is both safe and effective in a subgroup of CD20(+) patients with HD.

Phase 2 study of a combined immunochemotherapy using rituximab and fludarabine in patients with chronic lymphocytic leukemia.

This multicenter phase 2 trial investigated safety and efficacy of a new immunochemotherapeutic regimen combining rituximab (R) and fludarabine (F) in patients with fludarabine- and anthracycline-naive chronic lymphocytic leukemia (CLL). The rationale for using R + F includes single-agent efficacy of both drugs, in vitro synergism of R and F, and no apparent overlapping toxicity. Of 31 eligible patients with B-CLL enrolled, 20 were previously untreated and 11 relapsed. Treatment consisted of fludarabine administered at standard doses (25 mg/m(2)/d; days 1-5, 29-33, 57-61, and 85-89) and rituximab (375 mg/m(2)/d) given on days 57, 85, 113, and 151. Side effects such as fever, chills, and exanthema were generally mild (National Cancer Institute Common Toxicity Criteria [NCI-CTC] grade 1/2 in 48% and grade 3 and/or 4 in 3% of patients). Fever and chills were mainly associated with the first rituximab infusion. Hematologic toxicity included neutropenia (grade 1 and/or 2 in 26%, grade 3 and/or 4 in 42%) and thrombocytopenia (grade 1 and/or 2 in 19%, grade 3 and/or 4 in 9%). One patient died of cerebral bleeding during prolonged thrombocytopenia after the second cycle of fludarabine. There were a total of 32 infections in 16 patients, none of which was fatal. The overall response rate (complete remission [CR] and partial remission [PR]) was 87% (27 of 31 evaluable patients). In 20 previously untreated patients, 17 (85%) responded. Ten of 31 patients achieved CR (5 of 20 untreated; 5 of 11 pretreated; 9 of 21 Binet stage B, 1 of 10 Binet stage C). The median duration of response was 75 weeks. We conclude that the combination of rituximab and fludarabine is feasible and effective in patients with B-CLL.