Treatment Of Low-grade non-Hodgkin's Lymphoma Research Articles

Bendamustine and rituximab and lenalidomide (BRR) in the treatment of relapsed and refractory low grade non-Hodgkin lymphoma (NHL): Final results of phase 1 study NCCTG N1088/ALLIANCE.

8540 Background: The combination of bendamustine and rituximab is effective in the treatment of low grade NHL. Lenalidomide shows significant synergy when combined with rituximab and rituximab-cont...

Vaccine strategies in the treatment of low-grade non-Hodgkin lymphoma

Recent years have witnessed the development of a variety of promising immunotherapies for treating patients with B-cell non-Hodgkin's lymphomas. Each B lymphocyte expresses an immunoglobulin molecule that is the product of a unique combination of gene segments. B cell malignancy arises from one original B lymphocyte, and therefore all the members of a given lymphoma tumor population have the same unique immunoglobulin, which can serve as a target for immune therapy. When the idiotype (Id), or unique portion, of each immunoglobulin is used as a vaccine, antibodies and T cells can be induced and each can cause rejection of the tumor by the host. This special opportunity for tumor specificity is accompanied by the challenge of constructing a different vaccine for each patient. The first clinical trial of Id vaccination for lymphoma was initiated at Stanford University in 1988. Tumor cells obtained from lymph node sampling were fused with a myeloma cell line to generate a “hybridoma” producing large quantities of idiotype protein. Purified Id protein was then chemically coupled to keyhole limpet hemocyanin (KLH) and emulsified in an “oil-in-water” type immunologic adjuvant. The initial trial included patients with low-grade, follicular lymphoma, in first remission following chemotherapy. Among the first 32 vaccinated patients, roughly half (14/32) developed anti-Id immune responses. These were principally humoral responses rather than cellular responses. Long-term follow-up of these 32 patients has revealed that the development of an immune response is strongly correlated with prolonged freedom from disease progression interval and overall survival. Further trials have confirmed significant clinical benefit following Id vaccination. There is reason for excitement about the prospects for effective vaccine therapies for lymphoma as randomized Id vaccine trials commence and newer cell-based vaccine trials enter the clinic. As the clinical activity of lymphoma vaccines becomes established, it will be important to determine how to best integrate active vaccination approaches with standard therapeutic approaches.

Treatment of Low-Grade Non-Hodgkin Lymphomas with Fludarabine and Mitoxantrone Followed by Rituximab Maintenance: Results of a Phase II Study.

The combination of fludarabine and mitoxantrone (FN) has been a well-tolerated and effective regimen for the treatment of indolent lymphomas. Rituximab is an active agent for the treatment of CD20-positive B-cell lymphomas. In the present study, we sought to determine the activity of FN chemotherapy followed by maintenance Rituximab in indolent lymphomas. Patients with indolent lymphoma received fludarabine 25 mg/m2 day 1–3 and mitoxantrone 10mg/m2 every 28 days. Patients who attained a response (CR or PR) received 4 weekly doses of Mabthera 375mg/m2 1 month and 3 months after completion of treatment. The primary endpoint of the study was to evaluate the response to this regimen and secondary endpoints were survival and toxicity. Forty-six patients were included in the study. The median follow-up time was 29 months. Six patients were stage I, 8 stage II, 3 stage III and 29 stage IV. Histology was distributed as follows: small lymphocytic lymphoma (SLL) 15 patients, splenic marginal zone lymphoma 3, lymphoplasmocytic lymphoma 1, marginal zone B-cell lymphoma 16 (extranodal 12 and nodal 4), follicular grade I 6 and follicular grade II 5 patients. The median number of delivered cycles was 6. Fifty-two percent of patients attained a complete response (CR) and 39% a partial response (PR) for an overall response rate of 91%. One patient had stable disease, one had progression of the disease, whereas 2 were non-evaluable. After a median follow-up of 29 months, 34 of 46 patients (74%) are alive and disease-free. Grade III and IV toxicities included neutropenia (28%), thrombocytopenia (7%), anemia (4%), and diarrhea (2%). In conclusion, FN followed by Rituximab maintenance is an active and well-tolerated regimen in the treatment of patients with indolent lymphomas.

Management of patients with post-transplant lymphoproliferative disorder: the role of rituximab

Post-transplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ and bone marrow transplantations. Rituximab (Rituxan, Mabthera), a chimeric monoclonal antibody to the CD20 antigen on the surface of B-cell lymphocytes, has been used increasingly in the treatment of PTLD. Rituximab was initially approved for the treatment of low-grade non-Hodgkin lymphomas, but multiple case studies, retrospective analyses, and phase II trials demonstrate the benefit of rituximab in PTLD. This paper reviews the current data on rituximab and its promising role in the management of PTLD.

Bendamustine in the treatment of non-Hodgkin's lymphoma: results and future perspectives.

Bendamustine has clinical potential in the treatment of low-grade non-Hodgkin's lymphoma (NHL). As a single agent, bendamustine has been used in two studies in patients with relapsed or refractory low-grade NHL. When bendamustine 120 mg/m(2) was given on days 1 and 2, the overall response rate was 73% with complete responses in 11%. When bendamustine 50 to 60 mg/m(2) was given on days 1 through 5, the overall response rate was 82.5%, with 14.5% complete responses. Bendamustine shows only partial cross-resistance with other agents used in the treatment of NHL and combination regimens have been investigated. The combination of bendamustine/vincristine/prednisolone (BOP) has been compared with cyclophosphamide/vincristine/prednisolone (COP) in a phase III study involving 162 patients with low-grade NHL. No differences were seen between the treatment arms with regard to response rate or survival, but the BOP regimen was significantly better tolerated than the COP regimen. The combination of rituximab/bendamustine has shown encouraging activity in patients with relapsed/refractory NHL and a trial is ongoing in which this combination is used in patients with advanced low-grade NHL or mantle cell lymphoma. Preliminary results from this trial are presented. The 93% overall response rate attained in the patients presently evaluable indicates that this combination is very active in this poor-prognosis population. Optimal treatment regimens with bendamustine in the treatment of low-grade NHL are yet to be defined, but results obtained to date indicate that further studies are warranted.