Alemtuzumab and Rituximab Combination Therapy for Patients with Untreated CLL – a Phase II Trial

• Published in: Blood 2008-11, Vol.112 (11), p.2098-2098
• Main Authors: Frankfurt, Olga, Hamilton, Elizabeth, Duffey, Sara, Acharya, Simbi, Raji, Adekunle, Ma, Shuo, Peterson, Loann, Goolsby, Charles, Rosen, Steven T.
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V112.11.2098.2098

Despite the availability of multiple therapeutic regimens, without a stem cell transplant, chronic lymphocytic leukemia (CLL) remains an incurable disease. A dramatic response rate with intensive chemo-immunotherapy in patients with CLL is frequently associated with irreversible long term consequences to the bone marrow, limiting further therapeutic options. For this reason we have initiated a clinical trial combining Rituximab (RIT) and Alemtuzumab (ALEM), two monoclonal antibodies with established activity and side effects profiles, as an initial therapy for patients with CLL requiring intervention. Methods: Data is available on 20 out of 21 enrolled patients. Therapy duration is 18 weeks. Subcutaneous (SQ) ALEM dose escalation: 3 mg - 10 mg - 30 mg on days 1, 3, 5, followed by the 30 mg Monday, Wednesday and Friday for 17 weeks. RIT at a dose of 375 mg/m2/dose IV is administered every other week staring on the 3d week for 8 doses. All patients received PCP, herpes virus, and fungal prophylaxis as well as CMV viral DNA monitoring. Responses were based on NCI-WG 1996 criteria; however, lymphadenopathy and organomegaly were also assessed by serial CT scans. Minimal residual disease (MRD) was measured in peripheral blood and bone marrow aspirate using flow cytometry for CD19+/CD5+/CD23 lymphocytes. Patients' characteristics: Since September 2005, 21 patients have been enrolled and 20 completed the therapy. All patients met ECOG criteria for requiring treatment. Median age was 54 years (28 – 74) with 12 males and 8 females; 19 Caucasian and 1 African American. The median time from the diagnosis to treatment was 21.5 months (2–144 months). Clinical stage (Rai) was I in 2 patients, II in 8 patients, III in 4, and IV in 6 patients. Median β2 microglobulin was 3.23 (0.34–15.3). Median WBC was 56 x109/L (17.4 – 157.6), Hgb 12.6 g/dL (10 – 14.7), and platelet count 172 x 109/L (66 – 307). Cytogenetic analysis, by FISH panel, was 13q- in 7, trisomy 12 in 6, and 13q-/11q- in 3, 11q- in 1, 11q-/p53/13q- in 1, and 13q-/11q-/6q- in 1 patient. Half of the patients were Zap70+ and 3 patients were CD38+. Mutational analysis is pending. Results: Based on the NCI-WG 1996 criteria, 15 patients (75%) achieved CR, 3 patients (15%) achieved PR, and 2 patients (10%) had stable disease. With utilization of CT scans responses were: 8 CR (40%), 9 PR (45%), and 3 SD (15%). At the completion of the study 14 patients (70%) had no evidence of MRD by flow cytometry. Median duration of t