ABSTRACT
Introduction. Monoclonal Gammopathy of Undetermined Significance (MGUS) is a pre-malignant plasma cell disorder reported in approximately 3% of individuals aged > 50 years, characterized by a low risk (about 1% per year) of evolution into “overt” myeloma or other lymphoproliferative diseases. It is classified as IgM-MGUS (15%) and non-IgM-MGUS (80-85%). MGUS is usually asymptomatic, but a higher risk of deep venous thrombosis and infection has been reported. In March 2020, “Coronavirus Disease 2019” (COVID-19) outbreak has been declared a pandemic by the World Health Organization. Regarding outcome of COVID-19 in patients with plasma cell dyscrasia, many papers have been published about multiple myeloma (MM), reporting a higher fatality rate respect to general population, while few data are available about the outcome of SARS-CoV-2 infection in patients with MGUS. Methods. We collected clinical data on MGUS Apulian patients with SARS- CoV-2 infection, tested by RT-PCR on nasopharyngeal swabs between March 1st, 2020 and April 30st, 2021. Among 1454 MGUS patients followed at our center, 91 were found SARS-CoV-2 positive, enrolled in this observational, retrospective study and compared with 182 age and sex-matched normal controls. Clinical data collected regarded: symptoms, hospitalization, hospitalization in intensive care unit, death. Calculations were carried out using Stata MP17. Results. Mean age of whole group (n. 273) was 65,3+/-13,3 years (range: 29-89), with no statistically-significant differences (p=0,734) observed between MGUS-group (65,6+/-13,3;range: 29-89 years) and controls-group (65,2+/- 13,4;range: 29-89 years). Mean number of comorbidities in the whole group was 1,2+/-1,2 (range: 0-5) and no statistically-significant differences (p=0,844) were found between MGUS-group (1,3+/-1,3;range: 0-5) and control group (1,2+/- 0,9;range: 0-3). About MGUS-subtypes, the most frequent was IgG-kappa (n=36;39,6%), followed by IgG-lambda (n=27;29,7%) and IgM-kappa (n=6;6,6%). Regarding MGUS risk-stratification, application of Mayo Clinic model identified 22 patients (24,2%) with low risk, 22 (24,2%) with low-intermediate risk, and 3 (3,3%) with high-intermediate risk;in 44 patients (48,3%) this data was missing. Immunoparesis was present in 13 cases (14,3%) and absent in 55 (60,4%), missing in 23 (25,3%). No patient developed MM or a lymphoproliferative disease progression during and immediately after COVID-19. Rates of symptoms (59,3% vs 56%), hospitalization (20,9% vs 14,3%), hospitalization in intensive care unit (11% vs 8,8%) and death (8,8% vs 5,5%) were slightly higher in MGUS group than controls (Table 1), but these differences were not statistically significant. A statistically significant association (p<0,05), was observed between higher age and death in both groups. Lastly, incidence of SARS-CoV-2 infection in MGUS patients (6,2%) was not statistically significant different from that observed in the population of the Puglia region (5,8%) in the same period. Conclusions. To our knowledge, this report is the largest study of patients with MGUS and SARS-CoV-2 infection to date. In our study patients with MGUS did not show an increased incidence of this infection compared to the general population and did not appear to represent a risk factor for poor outcome in COVID-19. [Formula presented] Disclosures: No relevant conflicts of interest to declare.
ABSTRACT
Cancer patients are at a higher risk of “Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)” infection than patients without cancer. In particular, Multiple Myeloma (MM) patients are at serious risk of contracting this severe infection because of many factors, such as immunosuppression, comorbidities, immune deregulation and frequent accesses to hospital. Several multicenter studies on MM patients and “Coronavirus Disease 2019” (COVID-19) have been published. At present, there are no proven agents for treatment or prevention of SARS-COV-2 infection, so single or combined therapeutic approaches repurposing existing anti-viral and anti-inflammatory drugs are currently utilized to treat patients with moderate to severe COVID-19. Among these, IL-6 inhibitors seem to be promising for the management of the massive cytokine storm associated with the development of the typical lung damage and consequent acute respiratory distress syndrome occurring in the most aggressive patterns of SARS-COV-2 infection. While different reports have been published about concomitant MM and Covid-19 infection, few data are available about the specific outcome of MM patients treated with IL-6 inhibitors. Available IL-6 inhibitors are siltuximab, tocilizumab and sarilumab. Siltuximab binds directly to IL-6, while tocilizumab and sarilumab target its soluble (sIL-6R) and membrane-bound receptors (mIL-6R). To our knowledge, from literature review, including case reports and case series, 49 patients (Table 1), with severe confirmed COVID-19 and MM, were treated with IL-6 inhibitors. The most used IL-6 inhibitor was tocilizumab, FDA approved for the management of CAR T-cell related Cytokine Release Syndrome (CRS) while no patient was reported treated with siltuximab. Clinical outcome (alive/deceased) is available for 40 on 49 patients with questionable results: 20 patients (50 %) died, 20 patients (50%) survived. Certainly, although this retrospective review includes a quite large cohort of patients (556), providing interesting information, several limitations to generalizability of findings are present. First, the number of patients with MM and COVID-19 infection treated with IL-6 inhibitors in the world, is certainly higher than one reported in case reports/case series. Second, data represent experiences of patients from different centers, treated differently in terms of drugs and according to their availability at different hospitals. Third, patients received also additional therapies for COVID-19 including hydroxychloroquine and anti-viral agents, so it is no possible distinguish absolutely the efficacy of tocilizumab (or other IL-6 inhibitors) from other drugs. An interesting aspect to focus on is the potential use of tocilizumab against MM. IL-6 is the major growth factor of human myeloma cells through an autocrine or a paracrine mechanism and tocilizumab was reported to inhibit their proliferation in vitro and to be effective in stabilize serum monoclonal protein in patients with systemic diseases (i.e. rheumatological disorders) and concomitant MM. So, in the subset of active MM patients with severe COVID-19 infection, in whom other anti-myeloma treatments could be not administrable, the possibility that tocilizumab could represent a treatment option with a double action against cytokine storm due to COVID-19 and MM itself would warrant to be verified.