LEEDS, England, May 3 /PRNewswire/ -- According to a study published in the May issue of the Journal of Clinical Oncology, 84 percent of patients who had no detectable traces of chronic lymphocytic leukemia (CLL) after receiving alemtuzumab had survived for at least five years. Peter Hillmen, M.D., and colleagues from the Leeds General Infirmary, Leeds, England, reported that the complete elimination of detectable diseased cells in patients with CLL is associated with a prolonged overall and treatment free survival. Alemtuzumab (marketed as MabCampath in Europe and as CamPath in the United States) is the first, and only, monoclonal antibody approved for the treatment of CLL.
"This study shows that it is possible to achieve responses when there is no detectable disease in patients with relapsed/refractory CLL and that this appears to extend the lives of most CLL patients beyond five years," said Dr. Hillmen. "The introduction of alemtuzumab as a cancer therapy has had a positive impact and improves overall survival in refractory CLL. The success in achieving MRD negative remissions in this heavily pre-treated group of patients is one of the essential steps towards our long-term goal of curing CLL," he explained.
The 18 patients (20%) who achieved the minimal residual disease-free endpoint after receiving MabCampath/CamPath had previously failed to respond or relapsed after receiving chemotherapy for their disease -- the criteria for taking part in the early clinical trials that took place July 1996 to May 2003. CLL patients who relapse from or are refractory to chemotherapy have the poorest prognosis with a median survival of 10 months.
Minimal residual disease (MRD) refers to the presence of leukemia cells in the bone marrow of patients in complete remission. Several retrospective and prospective studies indicate that analysis of MRD has prognostic value. Low levels or absence of MRD in the bone marrow after induction therapy are associated with positive prognosis.
"The results reported by Hillmen et al demonstrate that reduction in MRD below the level of detectability is achievable in CLL. It is exciting to know that patients are reaching a level of remission in which there is no evidence of any residual leukemic cells, as these patients have been found to have a better prognosis," said Kanti Rai, M.D., chief of the Division of Hematology and Oncology at the Long Island Jewish Medical Center, New Hyde Park, N.Y. "These advances are made possible by the development of a highly sensitive method of measuring MRD, as well as the emergence of alemtuzumab as a therapeutic tool in CLL."
The National Cancer Institute's definition of a complete response to therapy allows for up to 30 percent of morphologically normal lymphocytes in the bone marrow, and of these cells there can be up to five percent that are CLL cells. This five percent is thought to be responsible for the relapse of the disease eventually observed in patients with CLL. Modern techniques, such as four-color flow cytometry -- a column designed to filter out and detect diseased cells -- are far more sensitive than the light microscope which is traditionally used to detect diseased cells. Flow cytometry can detect as few as one single CLL cell in 100,000 cells.
Study Details
Patients and Methods: Ninety-one previously-treated patients with CLL (median age 58 years [range 32 to 75 years]; 44 were refractory to purine analogs) received a median of 12 weeks of alemtuzumab treatment. Regular bone marrow assessments by MRD flow cytometry were performed with the aim of eradicating detectable MRD (< 1 CLL cell in 105 normal cells).
Results: Responses according to National Cancer Institute-sponsored working group response criteria were complete response (CR) in 32 patients (36 percent), partial remission (PR) in 17 patients (19 percent), and no response (NR) in 42 patients (46 percent). Twenty-two (50 percent) of 44 purine analog-refractory patients responded to MabCampath/CamPath. Detectable CLL was eradicated from the blood and marrow in 18 patients (20 percent). Median survival was significantly longer for MRD-negative patients compared to those achieving an MRD-positive CR, PR, or NR. Patients achieving an MRD-negative CR experienced a longer period of treatment-free survival than patients with MRD-positive CRs, PR, or NR: MRD-negative CRs, not reached; MRD-positive CRs, 20 months; PRs, 13 months; NR, 6 months (P < .0001)]. Overall survival for the 18 patients with MRD-negative remissions was 84 percent at 60 months. Eight (47 percent) of the MRD- negative patients converted to MRD positivity at a median of 28 months.
About CLL
CLL is the most prevalent form of adult leukemia affecting approximately 120,000 people in the United States and Europe. The disease is characterized by the accumulation of functionally immature white blood cells (lymphocytes) in the bone marrow, blood, lymph tissue, and other organs. Two types of lymphocytes are present in the blood, B cells and T cells. About 95 percent of CLL cases involve cancerous B cells. Because leukemic B cells have a longer than normal life span, they begin to build up and "crowd out" the normal, healthy blood cells.
For further information, contact: Peter Hillmen, M.D. +44-113-392-5153
The Leeds Teaching HospitalsCONTACT: Peter Hillmen, M.D., +44-113-392-5153, for The Leeds Teaching