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Interim Data Analysis Finds SC MabCampath as Effective and Well-Tolerated as IV Therapy
ATLANTA, December 12/PRNewswire/ -- According to interim results from the Phase II UKCLL02 trial, when administered subcutaneously (SC), MabCampath(R) (alemtuzumab) is both effective and well-tolerated when compared to historical series of patients receiving intravenous (IV) therapy for fludarabine-refractory chronic lymphocytic leukemia (CLL). The results presented during the 47th annual meeting of the American Society of Hematology (ASH) demonstrated that nearly half of all patients treated with SC MabCampath achieved either partial or complete response with some patients achieving minimal residual disease negativity (MRD).
"While MabCampath IV has been successful in yielding response rates between 33 to 50 percent, infusion reactions and two-hour sessions, which occur three times a week for 12 weeks, can be both problematic in terms of side effects and time-consuming for patients," said Peter Hillmen, M.B, Ch.B, Consultant Haematologist, Leeds General Infirmary, Leeds, United Kingdom.
"These results are very encouraging for both patients and physicians as they demonstrate SC MabCampath appears to be as effective as traditional IV therapy. In these patients, who are very difficult to treat, SC therapy is better tolerated, providing added convenience."
Study Results
To date, of the first 44 patients assessed, 36 patients have completed therapy. The overall response rate for MabCampath and fludarabine therapy was 44 percent (39 percent with Campath alone); with three patients in the MabCampath monotherapy phase achieving complete response (two MRD negative and one MRD positive) and 11 achieving partial response (including one MRD negative patient who remained cytopenic). When treated with combined therapy with MabCampath and oral fludarabine two non-responders achieved partial response with one partial responder achieving a complete response (MRD positive). In addition, 20 patients with a genetic disposition toward poor response to chemotherapy (p53 dysfunction or deletion) responded well to MabCampath treatment.
The most common side effect during the initial MabCampath dose was localized erythematous skin reactions, fever and rigors, with all reactions subsiding within 48 hours of treatment. Grade 3+ thrombocytopenia and neutropenia were seen in 16 and 25 patients in the MabCampath monotherapy arm and in one and two patients in the combined therapy arm, respectively.
Potentially serious infections occurring with MabCampath monotherapy included CMV (cytomegalovirus) reactivation, febrile neutropenia, invasive fungal infection and pneumonia. Only CMV reactivation occurred with combination therapy patients and all CMV reactivations were resolved with antiviral therapy.
Comparatively, subcutaneous administration of MabCampath drastically reduced or even eliminated certain adverse event associated with intravenous administration, especially chills, rash and nausea/vomiting.
The median age for patients was 66 years (range 41 to 79), with 36 patients receiving 30mg doses of SC MabCampath three times a week for up to 24 weeks (depending on 6-weekly marrow assessments). Patients failing to achieve a response during the subcutaneous administration could receive 40mg/m2 of oral fludarabine for three days every four weeks in combination with SC MabCampath.
About Chronic Lymphocytic Leukemia (CLL)
CLL is the most prevalent form of adult leukemia, annually affecting approximately 120,000 people in Europe and the United States. 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. Because these B cells have a longer than normal life span, they begin to build up and "crowd out" the normal, healthy blood cells. The accumulation of functionally immature cells in the bone marrow excludes the generation of healthy cells and can become fatal.
Symptoms 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.
About MabCampath(R) (alemtuzumab)
MabCampath, also marketed as Campath(R) in the United States, is the first and only humanized monoclonal antibody approved for CLL and the first drug with proven efficacy in CLL patients who have failed both alkylating agents and Fludara (fludarabine phosphate) treatment. No other therapy has shown comparable efficacy in this group of patients. MabCampath/Campath has a completely different mode of action compared with conventional therapy by selectively targeting the CD52 antigen on the malignant lymphocytes. This activates processes leading to lysis, the death of the malignant cells. These processes result in the removal of the malignant lymphocytes from the bone marrow, blood, and other affected organs, which in turn can lead to an increase in life expectancy.
MabCampath demonstrates a side effect profile in this indication that can be safely managed with appropriate prophylaxis against and monitoring for opportunistic infections. These side effects are predictable, manageable and reversible. Furthermore, patients can form their own healthy blood cells once again as MabCampath does not attack the stem cells in the bone marrow.
Contact:
Greg Moulds
Head of Media Relations
Leeds Teaching Hospitals
+44-0113-2066244
Source: Leeds Teaching Hospitals
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