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Rituximab/Alemtuzumab May Be Beneficial for Poor-Prognosis Patients With Chronic Lymphoid Malignancies

Rituximab/Alemtuzumab May Be Beneficial for Poor-Prognosis Patients With Chronic Lymphoid Malignancies

HOUSTON-Both rituximab (Rituxan), an anti-CD20 monoclonal antibody, and alemtuzumab (Campath- 1H), an anti-CD52 monoclonal antibody, are effective in the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL). The response in some anatomic disease sites, however, such as lymph nodes and bone marrow, is unsatisfactory and neither antibody alone is curative. In relapsed/refractory CLL, response rates to single-agent alemtuzumab are typically 33% to 53%.[1-3] The combination of alemtuzumab with rituximab, however, yields higher response rates than alemtuzumab alone in patients with relapsed/refractory CLL, according to results presented by Stefan Faderl, MD, and colleagues from The University of Texas M.D. Anderson Cancer Center in Houston (ASH abstract 775).[4] Re-treatment Option The study involved a heterogeneous group of poor-prognosis patients with CLL and other chronic lymphoid malignancies that coexpress the CD20 and CD52 antigens. Rituximab was given at 375 mg/m2 intravenously weekly for four doses and alemtuzumab administered at 3, 10, and 30 mg intravenously on days 1 through 3 for week 1 and 30 mg thereafter on days 3 and 5 for weeks 2 through 4. Patients also received prophylactic trimethoprim-sulfamethoxazole and valacyclovir (Valtrex) during therapy. They were tested weekly for cytomegalovirus antigens in the blood. The protocol allowed the option of re-treatment with alemtuzumab and rituximab for up to three courses. A total of 48 patients with a median age of 62 years (range, 44 to 79 years) and a median of four prior therapies (range, one to nine prior therapies) were enrolled. Most (79%) patients had Rai stage 3 or greater disease and 54% had failed prior fludarabine (Fludara) therapy, with or without an alkylator. The majority, 32 patients, had CLL; 1 patient had prolymphocytic leukemia (PLL); 9 had CLL/PLL; 4 had mantle cell leukemia; and 2 had Richter's transformation. Responses Exceed 50% Among the 48 patients evaluable for response, 25 (52%) achieved a beneficial response. Complete response occurred in 8% of patients, nodular partial response in 4%, and partial response in 40% of patients. Among 32 patients with CLL, 20 (63%) responded, including two complete responses (CR) and one nodular partial response. No responses were observed in patients with mantle cell leukemia or Richter's. Of the 25 patients who responded, 90% had a complete response in blood, 37% had a complete response in bone marrow, 59% had improvement of at least 50% in lymph nodes, and 67% had at least 50% improvement in liver/spleen. Dr. Faderl suggested that these response rates were noteworthy and appeared to be higher than those seen with single-agent alemtuzumab, especially as almost all of these responses were acheived after only 4 weeks of therapy. The combination of alemtuzumab and rituximab was well tolerated. Most nonhematologic adverse events were infusion related and less than or equal to grade 2 by National Cancer Institute Common Toxicity Criteria. The most commonly reported adverse events included fever in 36 patients (75%), rigors in 32 (67%), skin reactions in 18 (38%), fatigue in 16 (33%), gastrointestinal symptoms in 13 (27%), and dyspnea in 12 (25%). Among the 48 patients in the study, infectious episodes occurred in 25 patients (52%). These episodes included cytomegalovirus reactivation in 13 patients (27%), which was symptomatic in 7 (15%), fever of unknown origin in 6 patients (13%), pneumonia in 5 patients (10%), and sinusitis in 3 patients (6%). These results, said Dr. Faderl, show that combination therapy with alemtuzumab and rituximab is feasible and that response rates appear to be improved relative to those observed with alemtuzumab alone. Given the poor prognosis of this patient population, the responses seen with this new combination therapy may provide an important contribution for further development of monoclonal antibody therapy.

References

1. Rai KR, Freter CE, Mercier RJ, et al: Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine. J Clin Oncol 20:3891-3897, 2002.
2. McCune SL, Gockerman JP, Moore JO, et al: Alemtuzumab in relapsed or refractory chronic lymphocytic leukemia and prolymphocytic leukemia. Leuk Lymphoma 43:1007-1011, 2002.
3. Keating MJ, Flinn I, Jain V, et al: Therapeutic role of alemtuzumab (Campath-1H) in patients who have failed fludarabine: results of a large international study. Blood 99:3554- 3561, 2002.
4. Faderl S, Thomas DA, O’Brien S, et al: Combined use of alemtuzumab and rituximab in patients with relapsed and refractory chronic lymphoid malignancies—An update of the M.D. Anderson experience (abstract 775). Blood 100:206a, 2002.
 
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