Early Infection Risk in Newly Diagnosed Multiple Myeloma Patients in the Modern Era

Background:

Multiple myeloma (MM) is the second most common hematologic malignancy, with an estimated 30,000 new cases in the United States annually. Advances in management of MM over the past 20 years have significantly improved outcomes, but MM continues to be an incurable disease. Infections continue to be a major cause of morbidity and mortality, with a high proportion of MM patient developing infections within the first 3 months of diagnosis. There have been limited data on infection rates in MM patients in community-based oncology setting over the past two decades. This study looked to define infection rates and associated risk factors in newly diagnosed MM patients within 90 days of initial diagnosis.

Methods:

A retrospective, observational study was conducted on MM patients ages 18-89 newly diagnosed January 1, 2010-December 31, 2018 within Kaiser Permanente Northern California. Patients were required to have a minimum of one year of membership prior to MM diagnosis. SEER data was used to identify MM patients, and clinical data were extracted from the electronic health record. Bacterial, viral, and fungal infections were identified using ICD9/ICD10 codes. Baseline demographic and clinical characteristics from visit notes, laboratory and pathology results, and transplant data from utilization and claims data were analyzed to assess infection risks. High-risk cytogenetics was defined as notation of the following in pathology reports or oncology notes: add 1q, t(4:14), t(14:16), t(14:20), deletion of 17p. Bivariate analyses were conducted to assess differences across groups using the chi-squared test and the Wilcoxon-Mann-Whitney nonparametric test.

Results:

A total of 2030 newly diagnosed MM patients identified for this study. Median age at diagnosis was and n=828 (40.8%) of patients were female. Among this cohort, 522 (25.7%) had an infection within 90 days of MM diagnosis. The median age of patients having infections was 71 years (IQR 63-80), and the median age of those not having infections was 68 years (IQR 60-76, p<0.001). The median Charlson Comorbidity Index (CCI) of patients having infections was 3 (IQR 1-5) and the median CCI of those not having infections was 2 (IQR 1-4, p<0.001). Patients having hemoglobin <10.0 g/dl were more likely to have infection than those having hemoglobin >10.0 g/dl (30.4% vs. 23.6% respectively, p=0.011). Similarly, patients presenting with hypercalcemia (calcium >11.0 mg/dL) were more likely to have infection (37.4% vs. 24.6% in patients having calcium <11.0 mg/dL, p<0.001) as were patients with creatinine clearance <60.0 mL/min of those having <60.0 mL/min vs. 20.7% of those having >60.0 mL/min, p<0.001). Patients having indicators of high-risk cytogenetics were less likely to have infections within 90 days of diagnosis compared to those with standard risk cytogenetics (21.1% vs 26.2% respectively, p=0.031). We did not detect significant differences across transplant eligible status within the first year after diagnosis (22.1% infection among transplant eligible vs. 26.6% among those who were not transplant eligible, p=0.059) nor across sex (27.3% among females vs. 24.6% among males, p=0.176). Additionally, no significant differences in infection were detected across race and ethnicity (24.0% infection among Asian patients, 26.4% among Black patients, 27.7% among Hispanic patients, 25.5% among White patients, and 14.3% among patients having unknown or other race and ethnicity, p=0.741).

Conclusions:

In this community-based oncology study, infection within 90 days of diagnosis continues to be a significant complication of multiple myeloma and these results are comparable to previous studies. Risk factors for infection include age, CCI, standard risk cytogenetics, anemia, hypercalcemia, and renal failure. Stem cell transplant, sex and ethnicity were not associated with increased risk for infection. Future analysis will include assessments of hospitalization and mortality associated with infection. This study illustrates the importance of further research looking at decreasing infection rates in multiple myeloma patients.