Author(s): Lamanna N, Jurcic JG, Noy A, Maslak P, Gencarelli AN,
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Abstract PURPOSE: Modern combination strategies are active in chronic lymphocytic leukemia (CLL) but can have significant myelosuppression and immunosuppression that may require dose attenuation for safety. We explored a sequential treatment strategy to allow safe delivery of active agents at full doses. Previously, we studied sequential therapy with fludarabine followed by cyclophosphamide (F-->C). In that study, cyclophosphamide consolidation improved the frequency of complete response (CR) four-fold. Subsequently, rituximab was added to this regimen (F-->C-->R). PATIENTS AND METHODS: Thirty-six previously untreated CLL patients received therapy with fludarabine 25 mg/m(2) on days 1 through 5 every 4 weeks for six cycles, followed by consolidation with cyclophosphamide 3,000 mg/m(2) administered every 3 weeks for three cycles, followed by consolidation with weekly rituximab 375 mg/m(2) for four cycles. Evaluation for minimal residual disease included flow cytometry and a highly sensitive clonotypic polymerase chain reaction (PCR). The median age was 59 years (range, 37 to 71 years), 61\% of patients had high-risk disease, and 58\% had unmutated IgV(H) genes. RESULTS: There were 32 responses (89\%), including 22 CRs (61\%). Consolidation with cyclophosphamide improved responses in 13 patients (36\%); nine patients (25\%) further improved their response with rituximab. Twenty patients (56\%) achieved flow cytometric CRs, and 12 patients (33\%) achieved a molecular CR (PCR negative). Patients achieving molecular CRs had an excellent prognosis with a plateau in the response duration curve, and 90\% remain in clinical CR at 5 years. For the entire group, 5-year survival rate is 71\% compared with a rate of 48\% with our prior F-->C regimen (P = .10). CONCLUSION: Sequential therapy with F-->C-->R yields improvement in quality of response, with many patients achieving a PCR-negative state.
This article was published in J Clin Oncol
and referenced in Arts and Social Sciences Journal