Rituximab: Correlation Between Effector Cells and Clinical Activity in NHL

Publication
Article
OncologyONCOLOGY Vol 13 No 3
Volume 13
Issue 3

Unlabeled monoclonal antibodies (MoAbs) are attractive for the treatment of non-Hodgkin’s lymphoma (NHL) as they may: (1) mediate cytotoxicity with complement (complement-dependent cytotoxicity [CDC]) or effector cells (antibody-dependent cellular cytotoxicity [ADCC]); (2) effect apoptosis; (3) be less toxic, less immunogenic, and more effective than toxin- or drug-conjugated MoAbs; (4) not require the complex procedures needed for radiolabeled MoAb therapy (RIT); and (5) not produce the myelosuppression typical of high-dose RIT.

Unlabeled monoclonal antibodies (MoAbs) are attractive for the treatment of non-Hodgkin’s lymphoma (NHL) as they may: (1) mediate cytotoxicity with complement (complement-dependent cytotoxicity [CDC]) or effector cells (antibody-dependent cellular cytotoxicity [ADCC]); (2) effect apoptosis; (3) be less toxic, less immunogenic, and more effective than toxin- or drug-conjugated MoAbs; (4) not require the complex procedures needed for radiolabeled MoAb therapy (RIT); and (5) not produce the myelosuppression typical of high-dose RIT.

The anti-CD20 MoAb, rituximab (Rituxan) has low toxicity and significant activity. It is approved for the treatment of relapsed or refractory, low-grade or follicular NHL. In a single-agent study of 166 patients with refractory, low-grade or follicular NHL treated with rituximab at 375 mg/m² weekly for four infusions, the overall response rate was 48% (6% complete response [CR] and 42% partial response [PR]). Median time to progression for responders was 13.2 months and duration of response 11.6 months.

Median circulating B-lymphocyte counts dropped to 0 following the first dose. CD3, CD4, CD8, and natural killer (NK) cell counts remained unchanged. B-cell recovery in peripheral blood began at 6-9 months and was complete by 9-12 months. No significant changes in serum complement levels were noted.

The mechanism of action remains unresolved, with CDC, ADCC, apoptosis, and/or other mechanisms being considered. Humanized and chimeric antibodies are more likely to mediate/activate human effector functions. We have observed a correlation between higher absolute NK cell count at baseline and response to the MoAb.

CONCLUSION: ADCC may be an important mechanism for the clinical activity seen in patients treated with rituximab. Agents that increase effector cell number and function may enhance the MoAb’s clinical activity. Studies of rituximab in combination with interleukin-2 (IL-2), granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon (INF), and other agents are in progress.

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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