Treatment options for patients with relapsed chronic lymphocytic
leukemia (CLL) are limited. In this report, we present our preliminary results
of a biochemotherapy combination using rituximab (Rituxan, a monoclonal antibody
against CD20) with fludarabine (Fludara) and cyclophosphamide (Cytoxan, Neosar).
During course 1, rituximab is given at a slow rate at 375 mg/m2 on day 1
followed by fludarabine at 25 mg/m2 and cyclophosphamide at 250 mg/m2 on days 2-4.
During subsequent courses (2-6), rituximab is given at 500 mg/m2 on day 1 and
fludarabine and cyclophosphamide are given at the same doses but on days 1-3.
Of 84 patients registered, 43 are currently evaluable after more than 3 courses.
Patients had a median age of 57 years (range: 18 to 74 years),
65.1% were male, and 44% were Rai stage IV. The median platelet count was 110
(range: 15 to 367), median hemoglobin was 12.2 (range: 6.8 to 16.0), and median
white blood cell count was 45.8 (range: 2.7 to 311). Three or more lymph node
sites were involved in 58%, B2 microglobulin was greater than 3 in 79%, and 83%
had a performance status of 1 or less. Of the 43 patients, 1 had splenic
lymphoma with villous lymphocytes and 1 had marginal zone lymphoma. The median
number of prior treatments was 3: 9.3% of patients had received alkylating
agents only, 65.1% had been sensitive to fludarabine-containing regimens, and
20.9% had been resistant to fludarabine. The median follow-up time is 5 months.
Using National Cancer Institute criteria, the complete remission
(CR) rate is 14% (all in the fludarabine-sensitive group, 21%), nodular partial
response (PR) 14%, PR 42%, stabilization of disease 4.7%, and no response 20.9%.
Total response rate is 69.9%. One patient died early. Five other patients have
died (none during the first course), 3 of them due to progression of disease.
Serious toxicities from the treatment include 8 episodes of pneumonia, 4
episodes of neutropenic fever, 2 of sepsis, and 1 prolonged myelosupression.
Other frequent toxicities related to rituximab include fever, chills, and
nausea; hypotension occurred in 5 (12%) patients.
CONCLUSION: In summary, fludarabine, cyclophosphamide, and
rituximab is a very active and well-tolerated program for patients with
previously treated CLL, in particular for fludarabine-sensitive disease. Studies
evaluating the efficacy and toxicity of this program are ongoing.