Infectious Complications and Their Relationship with Mortality in Patients Newly Diagnosed with Multiple Myeloma

INTRODUCTION.

Early mortality after diagnosis of Multiple Myeloma (MM) is common and frequently associated with infections. A Danish study reported a mortality of 22% among the first 180 days with infections being responsible for 50.9% of deaths. Treatment for MM has been related with infections in some studies, but this data is not consistent.

Infections typically occur during the first months after MM diagnosis and initiation of treatment. In Latin America there is a lack of information about infections in patients diagnosed with MM, with only one study reporting a prevalence of 35.9% within the first 6 months, and most of them, 67.3%, during the first 3 months.

To describe infections and to evaluate potential risk factors associated with them could help to improve the care of patients with MM.

METHODS

We conducted a retrospective cohort from a tertiary referral center in Mexico City. We included patients diagnosed with MM according to the International Myeloma Working Group criteria, between January 2017 and December 2020. Baseline clinical characteristics, disease parameters and infections at or after the MM diagnosis were collected, as well as the etiologic agents and their outcomes.

The primary outcome was to describe the infectious complications of patients with MM in the first 6 months after diagnosis. The secondary outcome was to identify risk factors for early mortality defined as death during the first 6 months after diagnosis.

Baseline characteristics and infections were described using mean and standard deviation or median and interquartile ranges. For the secondary outcome, patients were analysed in two groups depending in the presence of infections or not. Comparisons between groups were made by chi square, Fisher's exact test, t-tests, and rank-sum test; multivariate analysis by means of a logistic regression was performed. Two-sided p-values of <0.05 were considered statistically significant. All analysis were performed using STATA version 15.1.

RESULTS

Eighty-two patients were diagnosed and included in the study in the specific period. Median age was 66.5 and 56% were male. Median follow-up time was 28.6 months; 49/82 (60%) developed > 1 infections, of which 33/49 (67%) were in the first 4 months after MM diagnosis and 16/33 patients (48%) experienced two or more episodes. Distribution of infections was as follows: lower respiratory tract (45%), urinary tract (24%), gastrointestinal tract (9%) and primary bacteriemia (6%). Bacteria were the most common etiologic agents.

There were 3 cases of Clostridium difficile infection documented during the second and third episodes of infection. The mortality associated with this infection was very high (66%).

High plasma cell infiltration in bone marrow aspirate (p=0.03), increased kappa free light chain concentration (p=0.02), lower hemoglobin concentration (p=0.003), decreased serum albumin (p=0.004) and high serum globulin concentration (p=0.04) were associated with infection. Alkylating agents were the only treatment associated with increased risk of infection (p=0.05).

Overall mortality during the first 6 months was 11%. There was a significantly higher cumulative risk (46.4%) of early death in patients who developed infections, compared to those who did not.

CONCLUSIONS.

Sixty percent newly diagnosed MM developed infections during the first 6 months after diagnosis. The most common affected sites were lower respiratory tract, urinary tract, gastrointestinal tract and primary bacteriemia.

Sixty-seven percent of the infectious episodes were developed among the first four months after the diagnosis.

The most common etiologic agents were bacteria. There were two episodes of infections caused by candida SPP and three caused by influenza virus. Gram-negative bacteria were the most common bacteria isolated during the second and third episodes, with 3 cases of Clostridium difficile infection.

Infections were responsible of 46.4% more early deaths in newly diagnosed MM patients compared to those that did not have infections. High tumor burden characteristics were associated with greater risk of infections.

Aguayo:Roche: Speakers Bureau. Martínez-Baños:Sanofi: Speakers Bureau; Amgen: Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.