Rituximab Therapy in Previously Treated Waldenström’s Macroglobulinemia: Preliminary Evidence of Activity

Publication
Article
OncologyONCOLOGY Vol 13 No 3
Volume 13
Issue 3

Waldenström’s macroglobulinemia is a rare, low-grade lymphoproliferative disorder for which few therapies are effective. Although patients with Waldenström’s macroglobulinemia often are reported with cases of small lymphocytic lymphoma, this disease has characteristic lymphoplasmacytic histology, bright CD20 expression, and IgM paraproteinemia. Rituximab (Rituxan) is a chimeric anti-CD20 monoclonal antibody that produces a 50% response rate in previously treated low-grade lymphoma, but has no previously described efficacy in the Waldenström’s macroglobulinemia subtype. We report 7 patients with Waldenström’s macroglobulinemia treated on clinical trials performed by IDEC Pharmaceuticals (N = 6) or at our institution (N = 1). Characteristics of these patients included a median age of 60 years (range, 50-75 years) with 5 being female. All patients were symptomatic, with a median performance status of 1 (range, 1-3), with all having measurable disease independent of paraproteinemia.

Waldenström’s macroglobulinemia is a rare, low-grade lymphoproliferative disorder for which few therapies are effective. Although patients with Waldenström’s macroglobulinemia often are reported with cases of small lymphocytic lymphoma, this disease has characteristic lymphoplasmacytic histology, bright CD20 expression, and IgM paraproteinemia. Rituximab (Rituxan) is a chimeric anti-CD20 monoclonal antibody that produces a 50% response rate in previously treated low-grade lymphoma, but has no previously described efficacy in the Waldenström’s macroglobulinemia subtype. We report 7 patients with Waldenström’s macroglobulinemia treated on clinical trials performed by IDEC Pharmaceuticals (N = 6) or at our institution (N = 1). Characteristics of these patients included a median age of 60 years (range, 50-75 years) with 5 being female. All patients were symptomatic, with a median performance status of 1 (range, 1-3), with all having measurable disease independent of paraproteinemia.

Patients were heavily pretreated, having received a median of three (range, one to four) prior therapies for their Waldenström’s macroglobulinemia. Prior therapy had included an alkylator in all patients (5 refractory) and fludarabine in 4 (all refractory), with 5 being refractory to their last therapy. Pretreatment laboratory features included a mean serum IgM of 2.9 g/dL (range, 0.72-6.28 g/dL); leukocyte count, 5.1/cm³ (3.0-6.6/cm³); hemoglobin, 10.5 g/dL (8.6-13.4 g/dL); and platelets, 219/cm³ (32-332/cm³).

All patients received rituximab (375 mg/m²) weekly for 4 weeks (N = 6) or 8 weeks (N = 1) . Therapy was well tolerated, with five patients having infusion-related toxicity (four grade 1/one grade 3) during the first therapy. Cellular immune function, as measured by mean CD4 lymphocyte counts (pretreatment, 344/mm³ vs 3 months posttreatment, 331/mm³; P = .89) and mean CD8 lymphocyte counts (pretreatment, 608/m³ vs 3 months posttreatment, 654/mm³; P = .32) were not significantly altered by rituximab therapy. Corresponding with this was the absence of opportunistic infections and only one posttherapy grade 3 bacterial sinusitis.

Responses, as assessed by at least 50% reduction in all measurable disease (non-Hodgkin’s lymphoma partial response) occurred in four (57%) patients, while a 50% reduction in paraproteinemia (Waldenström’s macroglobulinemia partial response) was noted in three (43%) of these same patients. The median progression-free survival for these seven patients was 8 months (range, 3-27+ months).

CONCLUSION: These preliminary data suggest that rituximab has clinical activity in pretreated Waldenström’s macroglobulinemia without decrements in hematologic or cellular immune parameters that are commonly noted with other therapies employed in this disease. Based on these data, future studies utilizing rituximab in both previously treated and untreated Waldenström’s macroglobulinemia appear warranted. 

Click here for Dr. Bruce Cheson’s commentary on this abstract.

Articles in this issue

WHO Declares Lymphatic Mapping to Be the Standard of Care for Melanoma
Rituximab: Phase II Retreatment Study in Patients With Low-Grade or Follicular Non-Hodgkin’s Lymphoma
Response Criteria for NHL: Importance of “Normal” Lymph Node Size and Correlations With Response
Chemotherapy Plus Radiation Improves Survival in Patients With Cervical Cancer
A Randomized Trial of Fludarabine, Mitoxantrone (FM) Versus Doxorubicin, Cyclophosphamide, Vindesine, Prednisone (CHEP) as First Line Treatment in Patients With Advanced Low-Grade Non-Hodgkin's Lymphoma: A Multicenter Study by GOELAMS Group
Navelbine Increased Elderly Lung Cancer Patients’ Survival
Fludarabine Versus Conventional CVP Chemotherapy in Newly C Diagnosed Patients With Stages III and IV Low-Grade Malignant Non-Hodgkin’s Lymphoma: Preliminary Results From a Prospective, Randomized Phase III Clinical Trial in 381 Patients
Multicenter, Phase III Study of Iodine-131 Tositumomab (Anti-B1 Antibody) for Chemotherapy-Refractory Low-Grade or Transformed Low-Grade Non-Hodgkin’s Lymphoma
T-Cell–Depleted Allogeneic Bone Marrow Transplant From HLA-Matched Sibling Donors for Non-Hodgkin’s Lymphoma
Consensus Statement on Prevention and Early Diagnosis of Lung Cancer
In Vivo Purging and Adjuvant Immunotherapy With Rituximab During PBSC Transplant For NHL
Fludarabine and Cyclophosphamide: A Highly Active and Well-Tolerated Regimen for Patients With Previously Untreated Indolent Lymphomas
Campath-1H Monoclonal Antibody in Therapy for Advanced Low-Grade Non-Hodgkin’s Lymphomas: A Phase II Study
AIDS Drugs Effective Against Most Common HIV Strain
Rituximab Therapy in Previously Treated Waldenström’s Macroglobulinemia: Preliminary Evidence of Activity
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