ATLANTA, Dec. 12 /PRNewswire/ -- New data presented at the 47th Annual Meeting of the American Society of Hematology (ASH) suggest that granulocyte macrophage colony stimulating factor (GM-CSF) may safely and effectively augment the efficacy of rituximab in the treatment of relapsed follicular lymphoma (FL).
Follicular lymphoma is a common type of Non-Hodgkin’s Lymphoma (NHL), making up about 25 percent of all cases of the incurable disease.
In the Phase 2 study, patients received a combination of rituximab and GM-CSF for four cycles of therapy. The complete response (CR) rate achieved with the combination therapy was 44 percent, and the overall response (OR) rate was 68 percent for the 33 intent-to-treat patients with relapsed FL. The median progression-free survival was 16.7 months.
Typical CR achieved with monotherapy rituximab is 5-16 percent in relapsed follicular lymphoma.
“GM-CSF is a biologic agent capable of enhancing proliferation of cell populations and cell surface receptors necessary for rituximab activity. Data from a similar study presented earlier this year demonstrated that the GM-CSF Leukine(R) appeared to improve the efficacy of rituximab in treating the most common form of Non-Hodgkin’s lymphoma,” said Jean-Francois Rossi, M.D., lead investigator and professor, Department of Hematology/Oncology and Unit of Cellular Therapy at the University Hospital, Montpellier, France. “Like investigators from the Leukine study, we hypothesized that the combination of GM-CSF and rituximab would substantially improve the treatment efficacy of rituximab in relapsed follicular lymphoma patients.
“The relatively high response rate in our study, as well as the longer-than-expected duration of response to therapy, are encouraging news for patients suffering from this incurable disease,” Rossi added. “These results suggest that the combination of GM-CSF and rituximab is a safe and effective regimen for the treatment of follicular lymphoma and certainly warrants further investigation.”
About the Study
In the study, a total of 46 patients with a median age of 60 years (range, 37 - 80 years) received rituximab and GM-CSF between January 2000 and October 2000. This analysis focuses on 34 patients with relapsed FL, assessing the clinical response, biologic response, and safety of combination rituximab and GM-CSF therapy. GM-CSF was administered at 5 mcg/kg/day on Days 1 - 8 and rituximab was administered at 375 mg/m(2)/week on Day 5 of each 21-day cycle for a total of 4 cycles. Response was evaluated at Days 30, 60, 90, and every four months until progression. Of the 34 enrolled patients, one patient was excluded due to transformation and four patients withdrew from the study due to toxicity.
The CR rate was 44 percent and the overall response rate was 68 percent (15 CR + CR unconfirmed and 8 partial responses [PR]) for the 33 intent-to- treat patients with relapsed FL. CR was reached in 63% (7 of 11) patients who received at least three lines of previous therapy (range, 3 - 7 lines). The median progression-free survival was 16.7 months. A significant increase (P <0.01) in cell populations involved in antibody dependent cellular cytotoxicity (ADCC) activity, an immune response that makes cancer cells vulnerable to attack by immune cells, was demonstrated after rituximab/GM-CSF therapy.
In an effort to determine if a subset of patients may be more responsive to the rituximab/ GM-CSF combination, expression of dendritic cell subpopulations 1 and 2 (DC-1 and DC-2) were measured before and after treatment. Patients who achieved a CR had significantly lower DC-2 expression than patients achieving a PR (P = 0.012).
About Non-Hodgkin’s Lymphoma
It is estimated that nearly 200,000 people are living with Non-Hodgkin’s lymphoma (NHL) in the United States. NHL is a type of malignant disease that occurs within the lymphatic system. It originates from lymphocytes, a type of white blood cells, which can be divided into two main types, B lymphocytes and T lymphocytes (also called B-cells or T-cells). In adults, approximately 85 percent of NHL cases are of B-cell origin. NHL is the most commonly diagnosed malignant hematological disease and among the fastest growing cancers in the world.
Non-Hodgkin’s lymphomas can be divided clinically into two general categories: indolent lymphomas, which tend to grow relatively slowly, and aggressive lymphomas, which grow more rapidly. Indolent lymphomas include follicular NHL and were formerly commonly classified as “low-grade.” The average length of survival for patients with indolent lymphomas has been estimated between six and ten years. The median age at diagnosis is 55-60 years. NHL is slightly more common in men than women. Typically, the disease advances or transforms over time and because indolent lymphomas are usually not curable, these patients need new treatment alternatives.
Symptoms of NHL can be subtle. The most common sign is swollen lymph nodes in the neck or underarm. Secondary symptoms include chills, fever, night sweats, unexplained weight loss, lethargy and itching. Since these are also symptoms of cold or flu, it can be difficult to discern the disease from a fleeting illness or respiratory infection. When leukemia or lymphoma is suspected a physician performs a biopsy of the lymph nodes. Microscopic analysis of the blood cells found in the biopsy tissue help the pathologist to distinguish NHL from Hodgkin’s disease and other hematological malignancies. Within NHL, the rate of growth is important to determining disease category.
Contact: Marybeth Quane 212.299.8972 Marybeth.Quane@zenogroup.com Smitha Dwarakanath 212-299-8981 Smitha.Dwarakanath@zenogroup.com
Jean-Francois Rossi, M.D.
CONTACT: Marybeth Quane, +1-212-299-8972, Marybeth.Quane@zenogroup.com,or, Smitha Dwarakanath, +1-212-299-8981, Smitha.Dwarakanath@zenogroup.com
