SAN DIEGO, Dec. 9 /PRNewswire/ -- New data from a trial to evaluate the efficacy of Campath(R) (alemtuzumab) for the elimination of minimal residual disease (MRD) after chemotherapy in patients with chronic lymphocytic leukemia (CLL) show Campath cleared residual bone marrow disease in most patients and a molecular remission was achieved in 11 of 29 patients (38 percent) in whom polymerase chain reaction (PCR) results were available. The overall response rate was 46 percent. These data were presented yesterday at the American Society of Hematology 45th Annual Meeting and Exposition.
Additionally, patients treated at a higher dose of Campath had a higher response rate than those treated at a lower dose (52 percent versus 39 percent, respectively). This was not statistically significant, which is possibly due to the small numbers. Median time to progression is 42 months. Adverse events were manageable and reversible.
“These and other data being presented at ASH are encouraging because they demonstrate that Campath is a safe and effective treatment that induces a durable response in CLL patients who show evidence of residual disease following chemotherapy,” said lead investigator Susan M. O’Brien, M.D., professor in the Department of Leukemia at The University of Texas M. D. Anderson Cancer Center in Houston. “Campath induced conversion from PR and nPR to CR, and MRD negativity in the bone marrow was achieved in nearly 40 percent of patients.”
In addition, Campath achieved significant clinical responses with minimal side effects. Infusion related events were minor and usually resolved after the initial doses, and other events we observed resolved either spontaneously or with treatment,” O’Brien continued.
Minimal Residual Disease (MRD)
A patient with leukemia is considered to be in complete remission (CR) when no blast cells are detected by light microscope examination of the bone marrow (BM). The sensitivity of this method is 1-5 percent. At the time of diagnosis, the number of leukemia cells is approximately 10(12), which means that a patient in CR can still harbor as many as 10(10) leukemia cells, cells which are responsible for relapse if they are not eradicated by chemotherapy. The elimination of minimal residual disease refers to the absence of leukemia cells in the BM and blood of patients in CR. Several retrospective and prospective studies indicate that analysis of MRD has prognostic value. Low levels or absence of MRD in BM after induction therapy are associated with positive prognosis.
Study Details
Patients with a partial remission (PR), nodular PR (nPR) or complete remission (CR) with evidence of disease on immunophenotyping were eligible. Campath was administered at a dose of 10 mg IV three times a week (TIW) for four weeks. After a rest period of four weeks, patients were re-evaluated, and if disease was present they could receive another four weeks at a dose of 30 mg TIW. All patients received prophylactic trimethoprim-sulfamethoxazole and valacyclovir. After analysis of the first 24 patients entered, the dose was changed to 30 mg TIW for four weeks with no further therapy for subsequent patients. Fifty-six patients were evaluable. Median age is 60 years (range, 44-79). At the start of treatment with Campath, 33 patients were in PR, 18 in nPR, and five in CR. Two patients were unevaluable for response and one patient died of pneumonia. The overall response rate was 46 percent. Nine of 23 patients (39 percent) at the 10 mg dose responded versus 17/33 (52 percent) treated at 30 mg (p = NS). Nine of 18 patients in nPR achieved CR and 13 of 33 patients in PR improved to nPR or CR. The major reason for failure to improve response was residual adenopathy. Bone marrow disease was eradicated more frequently than nodal disease. Residual bone marrow disease cleared in most patients and 11 of 29 patients (38 percent) achieved a molecular remission (PCR pending on other patients). Median time to progression is 42 months.
Infusion related events were common with the initial doses, but all were Grade 1-2. The main infections were reactivation of CMV. Three patients developed EBV reactivation. Two had spontaneous resolution of the EBV lymphoma and in one case the lymphoma resolved after treatment with cidofovir and immunoglobulin.
“Given the median number of prior treatment regimens was two, 42 months time to progression is encouraging,” Dr. O’Brien said.
About Campath
Campath is the first and only humanized monoclonal antibody approved for B-CLL and the first drug with proven efficacy in B-CLL patients who have failed both alkylating agents and fludarabine phosphate treatment. Alemtuzumab targets the CD52 antigen found on the surface of both cancerous and noncancerous lymphocytes, but not on the surface of cells that have the ability to mature and differentiate into new, healthy lymphocytes. This activity is called hematopoietic cell sparing, which refers to the absence of effect on the precursors of normal blood elements such as neutrophils, erythroid cells and platelets. Once alemtuzumab binds to the CD52 antigen on a lymphocyte, it works to kill the cell through a variety of mechanisms that seek out and selectively destroy the malignant cells through natural processes. It also stimulates the body’s natural defense mechanisms to destroy the malignant cell. These various mechanisms of action are likely responsible for the removal of malignant lymphocytes from the blood, spleen, and bone marrow after injection. Although alemtuzumab has some effect in removing malignant lymphocytes that have accumulated in the lymph nodes and extranodal masses, its activity is best at clearing the bone marrow of diseased cells, thus allowing the body to replenish healthy lymphocytes.
Alemtuzumab is approved as therapy for patients suffering from B-CLL when treatment with fludarabine phosphate, the second-line therapy for B-CLL, has failed or for patients with treatment-resistant (refractory) recurrent disease. The monoclonal antibody is currently being investigated as a first line therapy using subcutaneous administration and in a variety of treatment combinations and sequences that include fludarabine and other monoclonal antibodies, as a part of both first and second line therapies.
About B-CLL
B-CLL is the most prevalent form of adult leukemia, annually affecting approximately 50,000 people in the United States and 60,000 in Europe. The disease is most commonly diagnosed in people age 50 or older. CLL 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. The accumulation of functionally immature cells in the bone marrow impairs the generation of healthy cells and eventually is fatal. Symptoms of the disease include fatigue, bone pain, night sweats, and decreased appetite and weight loss, but bone marrow involvement also leads to weakening of the immune system, exposing the patient to a higher risk of infection.
MEDIA CONTACT: Kimberly Goldman 212-299-8979 kimberly.goldman@PR21.com
Susan M. O’Brien
CONTACT: Kimberly Goldman of PR 21, +1-212-299-8979,kimberly.goldman@PR21.com
