ATLANTA—A novel frontline regimen has shown efficacy in high-risk patients with chronic lymphocytic leukemia, with no significant increase in hematologic toxicity, compared with historical data on the standard regimen, said William Wierda, MD, PhD, of M.D. Anderson Cancer Center. He presented preliminary results of the ongoing chemoimmunotherapy trial at ASH 2007 (abstract 628).
In a prior study of chemoimmunotherapy for previously untreated CLL, Dr. Wierda and his colleagues found that the regimen of fludarabine, cyclophosphamide(Drug information on cyclophosphamide), and rituximab(Drug information on rituximab) (Rituxan) (FCR) was highly active, with a complete response (CR) rate of 70% and progression-free survival of 77 months (Tam CS et al: ASCO annual meeting 2007, abstract 7008).
Alemtuzumab (Campath), a humanized IgG1 monoclonal antibody targeting the CD52 antigen that is expressed by a variety of lymphoid neoplasms, has shown significant activity in fludarabine-refractory CLL patients.
An earlier trial of this agent in combination with FCR (CFAR regimen) in 80 heavily pretreated CLL patients produced a CR of 25% and overall response rate of 66%, with acceptable toxicity (Wierda WG et al: Blood 108:31, 2006).
The CFAR regimen was therefore evaluated in a single-arm phase II trial of chemonaive high-risk CLL patients. High-risk patients were those younger than age 70 with beta-2-microglobulin levels greater than twice normal.
Treatment consisted of cyclophosphamide 200 mg/m2 and fludarabine 20 mg/m2 on days 3-5; alemtuzumab(Drug information on alemtuzumab) 30 mg IV on days 1, 3, and 5; and rituximab 375 to 500 mg/m2 on day 2, given for 28 days for up to 6 planned courses.
Allopurinol was given during course 1 as prophylaxis for tumor lysis. Patients routinely received pegfilgrastim (Neulasta) on day 6. Antibiotic prophylaxis included TMP-SMZ DS, while valacyclovir (Valtrex) or valganciclovir (Valcyte) was given as HSV/CMV prophylaxis.
