Successive advances in CLL therapy have led to significant gains in response quality and remission duration but have not yet shown improved survival. An inherent limitation of randomised trials is the long followup required to demonstrate survival benefit in indolent diseases. In order to examine the effect of initial therapy on survival, we retrospectively analyzed the outcomes of patients treated on frontline protocols at the MD Anderson Cancer Center. Between 10/86 to 01/04, 616 patients received initial therapy with one of three fludarabine-based chemotherapy regimens. Patients in Cohort 1 (F; n=190) received fludarabine±prednisone, Cohort 2 (FC/M; n=140) fludarabine & cyclophosphamide or mitoxantrone, and Cohort 3 (FCR; n=286) FC & rituximab. Therapy indication and response assessment were as per the NCI 1996 Guidelines.
Patient characteristics: median age 57 years; male 67%; Rai intermediate/high risk, 60%/36%; performance status 2 or more, 3.5%; abnormal cytogenetics 27%; B2m 4mg/L or greater, 38%. Median followup was 176, 108 and 56 months for F, FC/M and FCR respectively. Excluding the effect of therapy, univariate predictors of survival were (p-value all <0.05): age, hemoglobin, B2m, abnormal cytogenetics, performance status, Rai stage, albumin and absolute lymphocyte count; only age, B2m and abnormal cytogenetics remained significant following Cox multivariate analysis. Incorporating the therapeutic regimen (F v FC v FCR) into the model, significant predictors for survival were: age (RR 1.05 per year; p<0.0001), FCR regimen (RR 0.42 vs F, 0.41 vs FC/M; p<0.001), high B2m (RR 1.13 per mg/L, p=0.001) and abnormal cytogenetics (RR 1.48, p=0.05). FCR significantly improved survival in the following adverse prognostic groups: age 60 or older (p=0.03), high-risk Rai stage (p=0.002), B2m 4mg/L or greater (p=0.005), performance status 2 or more (P=0.03) and abnormal cytogenetics not involving chromosome 17 (p=0.003). Patients with deletion or abnormality of the chromosome 17 had median survival of <24 months irrespective of treatment regimen. Our analysis underscores the importance of initial therapy choice in determining the survival of patients with CLL. Novel therapeutic strategies are required for patients with chromosome 17 deletion or abnormality.
Disclosures: The use of rituxan in CLL is investigational.; Dr Keating is a consultant to Genentech and Berlex.; Dr Keating receives research funding from Genentech and Berlex. Dr O’Brien receives research funding from Genentech, Biogen IDEC and Berlex. Dr Wierda receives research funding from Berlex.; Dr Keating receives honoraria from Genentech and Berlex.; Dr Keating is a member of the Speakers Bureau of Genentech and Berlex.