The Majority of Myeloma Patients Are Hypogonadal but This Is Not Associated with High Risk Cytogenetics
Authors: Snoad Beau , Hudzik Samantha , Sborov Douglas W , Williams Nita , Jones Desiree , Hofmeister Craig C 
Published: October 2019

Abstract
Introduction: Hypogonadism, i.e. low total testosterone, is present in approximately a quarter of men older than 70 years (Harman SM et al, J. Clin Endo & Met, 2001, PMID 11158037 and Wu FCW et al, J Clin Endo & M et, 2008, PMID 18270261). Myeloma patients are known to suffer from fatigue and decreased functional performance, mood disturbances, and anemia; similar trends have been found in people with hypogonadism. Cytogenetically high risk myeloma characterized by the amplification of 1q21 is associated with increased serum levels of soluble IL-6 receptor (sIL-6r) (Stephens OW, Blood, 2012, PMID 22072558). We hypothesized that total testosterone levels will be associated with overall survival from the time of diagnosis, presence of 1q21 amplification by CD138-selected FISH, anemia, and anti-depressant use.
Methods: The Buckeye Myeloma Registry (OSU 10115) opened in 2011 to enroll any patient with a plasma cell dyscrasia. Serum total testosterone was measured at the time of the initial clinic visit to the myeloma group at Ohio State. Less than 325 ng/dL was defined as the hypogonadal range, and testosterone was divided into <100 (group 1), 100-240 (group 2), 240-325 (group 3), and greater than 325 ng/dL (group 4), although normal testosterone decreases with age. Female patient testosterone levels were also analyzed and divided into <10 (group 1), 10-60 ng/dL (group 2), and >60 ng/dL (group 3). A retrospective chart review was initiated to review all myeloma patients with a serum testosterone drawn at the time of their initial clinic visit to OSU.
Results: Among 418 male MM patients, median age was 65 y.o. (range 24-95), 86% were Caucasian and 14% African-American, and the distribution of ISS stage was 32% stage 1, 22% stage 2, and 19% stage 3 with 28% missing staging data. Cytogenetic data was missing from 28% of patients.
Out of 418 male MM patients, 29 (7%) had serum testosterone <100, 202 (48%) with testosterone 100-240, 79 (19%) with testosterone 241-325, and 108 (26%) > 325 ng/dL. Out of 172 female MM patients, 44 (26%) had an undetectable serum testosterone, 120 (70%) with testosterone 10-60, and 8 (5%) with testosterone > 60. Among male MM patients, log-rank [Mantel-Cox] analysis of overall survival with serum testosterone including all 4 groups demonstrated no significant differences (p=0.917) with only 80 events. Among 275 male MM patients with cytogenetic information available, there was no correlation between presence of 1q21 trisomies or tetrasomies and overall survival (r=0.0714, p=0.238). There was a strong and expected correlation between testosterone and BMI (r=0.14, p=0.00468).
Among 161 total female MM patients, log-rank analysis with serum testosterone including all 3 groups also demonstrated no differences (p=0.416) with only 29 events in total. Among 101 females with cytogenetic information, there was also no correlation with 1q21 amplification (r=0.0895, p=0.373).
Conclusion: The majority of male MM patients (74%) have secondary hypogonadism and approximately half have total testosterone levels <240 ng/dL. Cox proportional hazards analyses of survival adjusted for significant univariate covariates will be presented at the meeting. Correlations with anemia and medication use (specifically opiates and anti-depressants) will also be presented at the meeting.

Disclosures
No relevant conflicts of interest to declare.