Pretreatment Factors Associated with Second Malignancies Occuring After Frontline Fludarabine, Cyclophosphamide, and Rituximab (FCR) in Patients with Chronic Lymphocytic Leukemia (CLL).

Abstract 3448 Poster Board III-336 Introduction Patients (pts) with CLL have more than twice the risk of developing second malignancies [1]. Frontline therapy with FCR was the strongest independent determinant of survival when compared to FC in patients with CLL in retrospective analysis [2]. This study aims to identify pretreatment factors that may be associated with the development of 2 nd malignancies in patients with CLL treated with FCR as initial therapy. Methods Our analysis includes pts with CLL treated between July 1999 and November 2003, on a Phase II trial of FCR as initial therapy. Patients who had developed a 2 nd malignancy prior to initiation of therapy were excluded. Patients were divided in 2 groups according to whether they developed a 2 nd malignancy during the follow up period. Time to 2 nd malignancy was defined as the time from treatment to the first occurrence of 2 nd malignancy. Chromosomal abnormalities were detected by metaphase karyotype of bone marrow leukemia cells. Patient characteristics, response to FCR, and overall survival were compared between the two groups using: Wilcoxon rank for continuous variables or Chi-square tests for categorical variables; Kaplan-Meier method was used to generate survival curves and log-rank test was used to assess differences in survival between subgroups. Responses were assessed by 1996 NCI-WG criteria after completion of treatment. Univariate and multivariate Cox proportional hazards model were fitted to assess the association between pts9 characteristics and the second malignancy-free survival. Results Among 300 pts with CLL treated with frontline FCR, 46 had a 2 nd cancer diagnosed prior to FCR were therefore excluded from this analysis, resulting in a total of 254 pts (85%). With a median follow-up of 76 months, 58 pts (23%) have developed a 2 nd malignancy. These included hematological malignancies n=20, non-melanoma skin cancer n=18, solid tumors n=15 and 5 patients have more than 1 type of malignancy. Pts who developed a 2 nd malignancy had significantly higher pretreatment percent of lymphocyte in the bone marrow (p=0.04), were less likely to have enlarged spleen size (p=0.024), and were more likely to have deletion of or abnormal chromosome 17 (p=0.008). The overall survival or the responses to treatment were not different between the 2 groups of pts. In the Cox proportional hazards model, abnormalities of chromosome 17 and 13 were statistically significantly associated with shorter time to 2 nd malignancy: HR, 9.79 (95% CI, 2.84 - 33.82), p=0.0003 and HR, 4.019 (95% CI, 1.41 - 11.42), p=0.009, respectively. Conclusion Chromosome 17 and 13 abnormalities identified by standard metaphase karyotype analysis were more common in patients with CLL who develop 2 nd malignancy after FCR therapy. The response rates and overall survival were not different between patients with CLL with or without 2 nd malignancy after frontline therapy with FCR. Tsimberidou AM, Wen S, McLaughlin P, et al., J Clin Oncol. 2009 Feb 20;27(6):904-10. Tam CS, O9Brien S, Wierda W, et. al., Blood. 2008 Aug 15;112(4):975-80. Univariate Cox proportional hazards model in estimating the associations between covariates and 2 nd malignancy free survival. Disclosures No relevant conflicts of interest to declare.