Other Malignancies in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Analysis of 2083 Patients.
Authors: Tsimberidou Apostolia-Maria , O’Brien Susan , McLaughlin Peter , Wen Sijin , Wierda William , Kantarjian Hagop M. , Manning John , Lerner Susan , Hess Mark , Freireich Emil J. , Keating Michael J. 
Published: October 2019

Abstract
Introduction: Other malignancies are reported to occur with increased frequency in patients with CLL/SLL because of disease- or therapy-related immunosuppression. The purpose of this study was to assess the frequency of other cancers in CLL/SLL patients and to compare presenting characteristics and clinical outcomes between CLL/SLL patients with and without other malignancies.
Patients and methods: We reviewed the records of patients diagnosed with CLL/SLL at The University of Texas M. D. Anderson Cancer Center from 1985 to 2005.
Results: Among 2189 consecutive patients with CLL/SLL, 2083 were evaluable and 572 (27.5%) had another cancer: 39.5% of patients were diagnosed with another cancer before CLL/SLL, 52% after CLL/SLL, 5% prior to and after CLL/SLL, and 3.5% simultaneously with CLL/SLL. Overall, 642 cancers were reported, including skin (30%), prostate (13%), and breast cancers (9%), melanoma (8%), lymphoma (8%), gastrointestinal (7%), lung (7%), urinary tract (5%), genital (4%) and myeloid tumors (2%), head and neck (2%), endocrine (2%), and brain cancer (1%), sarcoma (1%), and other cancers (1%). The median number of other cancers was 1 (range, 1–4). The median time to other cancers after CLL diagnosis was 3.4 years (range, 0–33 yrs). Other cancers were more common in patients with older age (p<0.0001), higher serum β2-microglobulin (p<0.0001) or creatinine levels (p=0.002), male gender (p=0.02), smoking history (p=0.02), lower albumin (p=0.02) or hemoglobin levels (p=0.04), 17p, 6q, or 11q deletion (p=0.03), and longer follow-up (p<0.0001). The median follow-up was 6.2 yrs. Overall survival was shorter in CLL/SLL patients with other cancers compared with those without cancer (median, 10.1 yrs vs. 15.5 yrs; p<0.0001). In treated patients with CLL, patients with other cancers had lower rates of response (59% vs. 65%, respectively; p =0.049), failure-free survival (median, 2.7 yrs vs. 3.5 yrs, respectively; p=0.002), and survival (median, 9.8 yrs vs. 13.1 yrs, respectively; p < 0.0001) compared with those without other cancers. Other malignancies were noted in 303 (28.3%) of 1069 patients who required therapy for CLL/SLL (median follow-up, 7.7 yrs [range, 0.1-33 yrs]) and in 268 (26.4%) of 1014 patients who did not require therapy (median follow-up, 4.7 yrs [range, 0–31 yrs]) (p= 0.35).
The ratio of secondary malignancies/treated patients by therapy was as follows: fludarabine (F)+/− prednisone, 44/173 (25%; median follow-up, 15.9 yrs); F+cyclophosphamide (C), 23/119 (19%; median follow-up, 10.8 yrs); F+mitoxantrone (M), 9/53 (17%; median follow-up, 12.5 yrs); FC+rituximab (R)/FCMR/FMR+dexamethasone (D), 54/492 (11%; median follow-up, 5.9 yrs); R+/−GM-CSF, 6/132 (5%; median follow-up, 1.5 yrs), other therapies, 18/100 (18%; median follow-up, 8.3 yrs).
Conclusions: Other cancers were noted in 27.5% of patients with CLL/SLL. Treated patients had similar rates of other cancers compared to untreated patients (p= 0.35). Other malignancies increased proportionally with time of follow-up and they were associated with inferior outcomes in patients who required therapy for CLL/SLL.