COVID-19 in Multiple Myeloma Patients: Frequencies and Risk Factors for Hospitalization, Ventilatory Support, Intensive Care Admission and Mortality -Cooperative Registry from Grupo Brasileiro De Mieloma Multiplo (GBRAM)
Authors: Garnica Marcia , De Queiroz Crusoe Edvan , Ribeiro Glaciano , Bittencourt Rosane , Magalhães Roberto José Pessoa , Zanella Karla Richter , Hallack Neto Abrahão Elias , Lima Juliana , Sola Caroline , Souza Emmanuella G , Magalhaes Andre , Maiolino Angelo , Hungria Vania 
Published: November 2021

Abstract
Patients with multiple myeloma (MM) have an increased risk for severe infections due to both the disease and anti-myeloma therapies. During the COVID-19 pandemic, case series of MM patients have demonstrated a poor outcome in those who required hospitalization due to COVID-19, and there are few data regarding those managed out of hospitals or risk factors for hospitalization. In Brazil, where the scenario is of restricted resources to treat MM patients and large numbers of COVID-19 cases and related death, the outcome can be even worse. Objective: To assess risk factors and outcomes of COVID-19 in Brazilian patients with MM.
This retrospective case series investigated 81 MM patients with documented COVID-19, managed in and out-hospital, from 8 states, representing 4 of 5 regions in Brazil. This study has been conducted by "Grupo Brasileiro de Mieloma" (GBRAM), and the present analyses included cases from April 2020 to July 2021. Clinical features and risk factors were analyzed with the severity of COVID-19 and outcomes (hospital admissions, intensive care unit (ICU) admission, ventilatory support, and death). The frequency of MM treatment modification due to COVID-19 was also accessed.
There were 81 MM patients (male 50%; median age 63 years; and ISS III at diagnosis 25%) diagnosed with COVID-19. At least one comorbidity was present in 47 (58%) patients: most frequently hypertension and diabetes (56% and 27%). Twenty-eight (35%) patients had more than one comorbidity. At COVID episode, 21 (26%) patients had an active disease or progression disease, and 40% received at least two prior lines of treatment. COVID-19 management required hospitalization in 49 (61%), ventilatory support in 30 (40%) and ICU in 28 (35%). Hospitalization was associated with age (p=0.008), presence of comorbidity (p=0.02), hypertension (p=0.02), presence of fever (p=0.005) and low respiratory symptoms (p=0.003). Ventilatory support was more frequent in patients with cardiac disease (p=0.05), receiving immunomodulatory (p=0.03), or monoclonal drugs (p=0.006). Patients receiving corticosteroids (p=0.02), immunomodulatory (p=0.06), or monoclonal drugs (p=0.06) in MM treatment had a higher frequency of ICU admission. By adjusted multivariate analysis, age, the clinical presentation with fever and low respiratory symptoms (p&lt;0.001, p=0.05 and p=0.001, respectively) were independent associated with hospitalization; low respiratory symptoms and MM therapy including monoclonal drugs (p=0.07 and p=0.02) were associated with ventilatory support; therapy with corticosteroids and immunomodulatory drugs (p=0.019 and p=0.05) were associated with ICU admission. Overall mortality was 29%. Mortality rates were 47%, 68%, and 77% in hospitalized, ventilatory support, and ICU patients, respectively. By univariate analysis, age, ECOG performance status, and MM therapy including corticosteroids, were associated with increased mortality. By multivariate model, only ECOG performance status remained as an independent risk factor for death. ISS, prior lines of therapy, prior stem cell transplantation, and disease status at COVID-19 were not associated with any analyzed outcomes. MM patients who recovered from COVID had the current MM treatment delayed in 61% of cases.
In this series, COVID-19 MM patients had a very high frequency of hospitalization, ventilatory support requirement, ICU admission, and deaths due to COVID-19. Although not associated with increased mortality, prior therapy drug classes were associated with severity of manifestation in our series. We also observed a high frequency of MM treatment delay in recovered patients, and the post-COVID clinical impact should be more explored. The high mortality observed reinforces the importance of preventing COVID-19, such as social distancing, wearing masks, and vaccination.

Disclosures
De Queiroz Crusoe: Janssen: Research Funding. Hungria: Takeda: Honoraria; Amgen, BMS, Celgene, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings/travel ; Abbvie: Honoraria; Sanofi: Honoraria, Other: Support for attending meetings/travel .