Second Cancers (SC) Affect the Clinical Outcome of Patients With Chronic Lymphocytic Leukemia (CLL) Treated With Frontline FCR Therapy

Abstract Abstract 2900 Increasing use of chemo-immunotherapy in CLL has raised concerns over the carcinogenic effect of FCR regimen. Fludarabine based regimen in relapsed CLL has been reported to be predisposed to a higher risk of other cancers as compared to healthy individual. However, an association between the CLL treatment and the development of other cancers is not evident in the frontline FCR setting. We retrospectively studied the frequency, characteristics, and clinical outcomes of second malignancy in patients with CLL who were treated with frontline FCR-based therapy at University of Texas, MD Anderson Cancer Center from 2004 to 2010. Patients who developed other malignancies after the initiation of FCR-based therapy were considered as patients with second cancer post CLL treatment (n=39). Patients who had history of other malignancies before the initiation of FCR-based therapy were considered as patients with prior malignancy history (n=90). Patients who neither have history of other cancers nor patients developed second cancer during the study period were assigned as patients without second cancer group (n=82). There were 24 patients (n=24) who experienced Richter's transformation post FCR-based therapy. The overall survival (OS) was measured from the initiation of CLL treatment until death from any causes or last follow-up. Progression-free survival (PFS) was measured from the initiation of CLL treatment until disease progression, relapse or death. Kaplan-Meier method was used to estimate outcomes in four groups. Cox-proportional hazard regression model was used to assess the association between patient characteristics and survival outcomes. Pre-treatment characteristics were similar among these groups except for chromosome abnormalities. Ten patients (44%) out of 24 patients with Richter’s transformation had TP53 gene mutation (p Thirty nine patients who developed second cancer includes non-melanoma skin (n=10, 26%), melanoma (n=2, 5%), head and neck (n=1, 2.5), Merkel cell (n=1, 2.5%), prostate (n=6, 15%), breast (n=1, 2.5%), lung (n=2, 5%) renal (n=1, 2.5%), gastric (n=2, 5%), liver (n=1, 2.5%), Hodgkin (n=1, 2.5%), and therapy-related MDS-AML (n=11, 28%). The estimated median PFS in the whole cohort was 4.57 years (95% CI: 3.678 to 5.462). PFS in patients without second cancer was not reached (NR) compared to 3.31 years (95% CI: 2.178 to 3.542) in patients with second cancer post CLL treatment (p The median follow up duration for all 235 patients was 3.29 years (range, 0.08–8.51 years) with total of 61 deaths. The median overall survival in either group of patients with prior malignancy history or in patients without second cancers were not reached (NR) compared with 3.81 years (95% CI: 2.231 to 5.389) in patients with second cancer (p There were 8 patients (10%) who died among 82 patients without second cancer as compared to 20 patients (49%) who died among 39 patients with second cancer (p Second cancers in patients with CLL treated with FCR regimen are significantly associated with inferior clinical outcomes. We observed the high incidence of skin cancer, prostate and Richter's transformation in patients with CLL who underwent treatment with frontline FCR-based therapy. Further studies are warranted to determine the association between FCR regimen and the development of second cancer, especially Richter's transformation. Download : Download high-res image (34KB) Download : Download full-size image Download : Download high-res image (38KB) Download : Download full-size image Disclosures: No relevant conflicts of interest to declare.