By Rafat Abonour, MD
2008-12-07
The introduction of newer agents with significant activity in chronic lymphocytic leukemia (CLL), particularly the purine analogs, and the application of autologous and allogeneic hematopoietic cell transplantation to the treatment of CLL has caused a shift in thinking, such that curative approaches are now being contemplated in younger patients. The oral and poster sessions this afternoon and on Monday morning will present data on old regimens, novel agents, and several combinations of old and new.
Alkylating agents seem to be important in managing the disease. During an oral session at 4:30 p.m., Dr. Neil Kay, from the Mayo Clinic, will show that increasing the purine nucleoside analogue dose does not eliminate the need to use the tried and true agent cyclophosphamide (abstract #43). Cyclophosphamide with pentostatin and rituximab was superior to pentostatin and rituximab. However, this was not a randomized study.
Immunomodulatory therapies (IMIDs) used widely in managing myeloma patients have made inroads into the management of CLL. Dr. Christine Chen, from Princess Margaret Hospital in Toronto, will report a phase II study on lenalidomide in managing symptomatic previously untreated CLL patients (abstract #44). Although tumor flare was most common in the first week on study, repeat flare symptoms with subsequent cycles were noted (30.6% of all 186 cycles). There were 11 partial responses (65%) and six stable diseases. Dr. Alessandra Ferrajoli, from the M. D. Anderson Cancer Center, will show that she used lenalidomide as an initial therapy in a group of elderly patients (abstract #45). In this ongoing study, 35 patients were evaluable for response with an overall response rate of 54 percent: 47 percent of the patients achieved a blood CR and 38 percent a blood PR using continuous therapy at a start dose of 5 mg followed by slow dose escalation.
At 5:15 p.m., Dr. Thomas Lin and colleagues from Ohio State will report on flavopiridol in high-risk relapsed CLL patients (abstract #46). Flavopiridol is a cyclin-dependent kinase inhibitor and induces p53-independent apoptosis of CLL cells in vitro. They report response and median progression-free survival results for patients with relapsed CLL (n=107) or small lymphocytic lymphoma (n=10) treated on successive phase I-II studies. Overall response rate (ORR) was 48 percent, including 52 partial responses (PR), 3 nodular PR (nPR), and 1 complete response (CR). These remarkable results will pave the way to novel combinations.
But, stay tuned on Monday. This day will belong to the first randomized study demonstrating that addition of rituximab to chemotherapy improves the outcome of patients with previously untreated advanced CLL. This important landmark study, which will be presented by Dr. Michael Hallek on behalf of the German CLL study group, will evaluate FCR versus FC (abstract #325). The overall response rate (ORR) was significantly higher in the FCR arm (95%; 370/390) compared to FC (88%; 328/371). The CR rate and progression-free survival, of the FCR arm was superior to the FC arm. As the follow-up is relatively short, we would not know the impact of FCR on overall survival, which remains an important goal. We’ll have to watch and wait for the results to mature.
Dr. Abonour indicated no relevant conflicts of interest.
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