Advanced disease and CD8 + TEMRA cells predict severe infections in Multiple Myeloma

Eva Tranter ^1* David Busch ¹ Clarissa Heck ¹ Igor Wolfgang Blau ¹ Axel Nogai ² Phillip Schiele ^1,3 Christian Meisel ^3,4,5 Lars Bullinger ^1,6,7 Marco Frentsch ^1,3 Il-Kang Na ^1,3,6,7

• ¹ Medical Clinic with a focus on Hematology, Oncology and Tumor immunology, Virchow Clinic Campus, Charité University Medicine Berlin, Berlin, Germany
• ² Onkologische Schwerpunktpraxis Tiergarten, Berlin, Germany
• ³ Berlin Institute of Health at Charité – Universitätsmedizin Berlin, BIH Center for Regenerative Therapies (BCRT), Berlin, Germany
• ⁴ Institute for Medical Immunology, Charité University Medicine Berlin, Berlin, Baden-Württemberg, Germany
• ⁵ Department of Immunology, Labor Berlin Charité Vivantes GmbH, Berlin, Baden-Württemberg, Germany
• ⁶ German Cancer Consortium (DKTK), Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
• ⁷ Experimental and Clinical Research Center, Charite University Medicine Berlin, Berlin, Baden-Wurttemberg, Germany

Infections are a major cause of early morbidity and mortality in patients with multiple myeloma (MM) who are characterized by immunodeficiency secondary to disease. However, prospectively collected data on infection risk in this population are scarce.We aimed at identifying parameters in monoclonal gammopathy of undetermined significance (MGUS) and newly diagnosed MM (NDMM) patients with predictive power for early severe infections (SI).We conducted a prospective study with newly diagnosed MGUS and NDMM patients. Besides clinical and laboratory data, immune parameters were collected at initial diagnosis before therapy initiation. Primary endpoint was the occurrence of SI within 12 months after diagnosis. 45% of patients developed infection, 26% with SI. Four main risk factors for SI were identified: ECOG ≥ 2 (p < 0.001), ISS stage II/III (p = 0.002), therapeutic intervention (p < 0.001), and elevated CD8 + TEMRA cells (p = 0.027). A risk score was compiled, enabling the stratification of patients with low or high risk for SI with a sensitivity of 92.9% and a specificity of 80%.We developed a straightforward risk score that considers the relevance of T cell fitness in MGUS and NDMM patients and can help physicians to identify patients at risk of infection, thus enabling the implementation of timely and individualized prevention strategies.