Associated Malignancies Among Patients and Kin with Waldenstrom's Macroglobulinemia
Authors: Hanzis Christina , Hunter Zachary , Manning Robert , Lewicki Megan , Brodsky Philip , Ioakimidis Leukothea , Tripsas Christina , Patterson Christopher , Sheehy Patricia , Treon Steven P. 
Published: October 2019

Abstract
Abstract 4159
Waldenstrom's macroglobulinemia (WM) is a B-cell malignancy characterized as an IgM secreting lymphoplasmacytic lymphoma. Familial predisposition is common in WM. Studies to date by us and others have revealed three identifiable clinical subtypes for WM predisposition:
* Sporadic; proband has WM, but there is an absence of WM or other B-cell disorders in other family members;
* Familial, Mixed B-cell Disorders Subtype; proband has WM, and various B-cell disorders are manifested by other family members.
* Familial, WM Only Subtype; proband has WM, and only WM is present in other family members;
While these studies suggest a separate genetic predisposition for WM, the correlation of additional cancer risk among all patients with WM and their kin, and well as those sub typed by familial WM predisposition may herald important information for common genetic risks to cancer. We therefore examined the incidence of additional malignancies in 923 consecutive WM patients seen at our Institution, and characterized the frequencies of additional malignancies based on familial subtype and against SEER data. In addition, we also characterized the incidence of solid cancers in kin of WM patients, and sub typed these cancers based on familial WM presentation.
Of the 923 patients, 221 (23.9%) patients had at least one additional malignancy to WM. Among these patients, 32 had 2, and 4 (0.43%) had 3 additional malignancies. For 167/221 (75.5%), the associated cancers were diagnosed before WM. The associated malignancies for all patients were as follows: Prostate (n=53; 9.2% of all males); Breast (n=27; 7.7% of all females); Skin (Basal and Squamous; n=61; 6.6%); Skin (Melanoma; n=16; 1.7%); Lung (n=12; 1.3%); Thyroid (n=10; 1.1%); Colorectal (n=7; 0.8%); Bladder (n=8; 0.9%) Other B-cell Malignancies (n=18; 2.0%); Renal (n=6; 0.7%); MDS (n=6; 0.65%); Other (n=11; 1.2%). The incidence of Lung (p=0.002) and Prostate (p=0.07) were higher among WM patients with Familial, Mixed B-cell Disorders Subtype.
To avoid potential treatment related impact on additional cancer development, we next adjusted the observed versus expected frequencies based on SEER-17 data. The age adjusted incidence for development of any malignancy among WM patients was 7.6 fold higher when the development of another cancer antedated the diagnosis of WM. Among all WM patients, the incidence of solid cancers among first degree kin were as follows: Prostate (n=98; 10.6%); Breast (n=133; 14.4%); Skin (Basal and Squamous; n=21; 2.3%); Skin (Melanoma; n=21; 2.3%); Lung (n=116; 12.5%); Thyroid (n=9; 1.0%), Colorectal (n=79; 8.6%); Renal (n=8; 0.9%); and Gastric (n=20; 2.2%). The incidence of Breast (p=0.0098), and Skin (Melanoma) (p=0.037) cancers were higher among first degree kin of patients with the Sporadic versus Familial, Mixed B-cell Disorders Subtype.
In summary, the above data suggest an increased risk for additional cancers among all WM patients, as well as specific risks for lung and prostate cancer among patients with Familial, Mixed B-cell Disorders Subtype. Moreover, these data also show the association of specific types of solid cancers in first degree kin of WM patients, particularly for WM patients with the Sporadic Subtype.
n= Age (Yrs) Gender % Treated Additional Cancers Sporadic 666 60 (29–91) 64% M; 36% F 515 (77%) 163 (24.4%) Familial, Mixed B–cell Disorders 212 58 (36–85) 57% M; 43% F 156 (73%) 50 (23.5%) Familial, WM Only 45 61 (35–89) 56% M; 44% F 35 (77%) 8 (17.7%) Total 923 59 (29–91) 62% M; 38% F 706 (76.4%) 221 (23.9%)

Disclosures:
No relevant conflicts of interest to declare.