Abstract
Despite the outstanding progresses in Multiple Myeloma treatment options in the last decades, it remains an incurable disease nowadays. Infectious events are a complication due to an impaired immune system associated with MM, sometimes a life-threatening one, particularly on the first months after the diagnosis. Both the underlying disease and treatment can contribute to the infection risk, so a biomarker that assess this risk could be highly relevant for a more tailored management of the patient. The measurement of the heavy+light chain (HLC) pairs of immunoglobulins in serum allows the quantification of both the monoclonal component and the non-monoclonal immunoglobulin of the same isotype. This approach has demonstrated high sensitivity for the detection of the clonality and prognostic value for MM. HLC pair suppression itself has prognostic power and it has been proposed to be a reflection of the immune system’ attempt to control the tumor. In this study we evaluated the impact of the HLC pair suppression on the rate of bloodstream infections (BSI) and early death in 115 newly diagnosed MM patients. Twenty-one percent of the patients suffered a BSI in the first 6 months after diagnosis, of which 58% died within this period, accounting to 67% of the early deaths in global and highlighting the major impact of infections on MM patients in a “real world” setting. Severe HLC pair suppression identified patients with a higher risk of early BSI (HR: 6,97, p=0,009), and extreme HLC pair suppression together with BSI event and age >65 were independent risk factors for early death (p<0,001). Based on these factors, a stratification model was generated to allow identify patients at a higher risk of early death and poorer OS, with an apparently better performance than the ISS on the early death context. In conclusion, HLC pair suppression associates with both a higher risk of life-threatening early infection and early death in newly diagnosed MM patients. Patients older than 65 with extreme HLC pair suppression and BSI are at a high risk of early death, and thus patients presenting with these criteria have a very adverse prognosis.
Highlights
Infection is an important cause of morbidity and mortality in severely immunocompromised patients with haematological malignancies undergoing chemotherapy or stem cell transplantation such as multiple myeloma (MM) [1]
The long-term survival of patients with haematological malignancies has improved during the last few decades, it has been recognised that infections are one of the most serious threats to these patients and where bacteraemia is frequent and is associated with high mortality rates [25,26,27,28]
In MM patients, bacteria are the most frequent aetiology agents invasive fungal infections caused by molds have been increasingly reported [10]
Summary
Infection is an important cause of morbidity and mortality in severely immunocompromised patients with haematological malignancies undergoing chemotherapy or stem cell transplantation such as multiple myeloma (MM) [1]. During the first 6 months after diagnosis, the risk of infection ranges from 20% to 55% and 10% to 25% of the deaths occurs during this period [12,13,14,15,16] In this context, it would be useful to have access to biomarkers that could accurately predict the risk of infection and early mortality associated to this cause. The objective of this study is to evaluate HLC pair suppression as a risk factor for bloodstream infections and early death in MM patients and compare it with the classical immunoparesis, i.e., suppression of the immunoglobulins not related to the monoclonal isotype (i.e. reduction of IgA and/or IgM in an IgG MM patient)
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