key: cord-0943214-vgwvih4b
authors: Susek, Katharina Helene; Gran, Charlotte; Ljunggren, Hans‐Gustaf; Alici, Evren; Nahi, Hareth
title: Outcome of COVID‐19 in multiple myeloma patients in relation to treatment
date: 2020-08-18
journal: Eur J Haematol
DOI: 10.1111/ejh.13502
sha: 41d2dc0f772c15aa23be5310d5683ab167fd39b2
doc_id: 943214
cord_uid: vgwvih4b

COVID‐19 has emerged as a global pandemic. Cancer patients have been reported to be at higher risk for adverse outcome of COVID‐19. Studies are ongoing to decipher the risk factors and risk groups among cancer patients as well as strategies to refine treatment approaches. Here, we report eight patients with multiple myeloma that underwent immunomodulatory therapies with daratumumab or lenalidomide‐based combination treatments and one patient with smoldering multiple myeloma, all of which presented with symptomatic COVID‐19. We report that patients that succumbed to COVID‐19 presented with either progressive tumor disease under daratumumab treatment or were in remission under lenalidomide‐dexamethasone treatment.

The coronavirus disease 2019 (COVID-19), caused by the coronavirus SARS-CoV-2, has become a global pandemic since its first emergence in late 2019. The clinical presentation varies among individuals with patients reporting only mild respiratory symptoms to severe lethal respiratory disease and multi-organ damage. 1 Risk factors for a severe course of the disease and adverse outcome are increased age, male gender, obesity, and other comorbidities. 2 Cancer patients are at higher risk to develop a severe form of COVID-19. 3 It is yet unclear whether the increased risk is associated with the malignancy, treatment strategies, or other possible iatrogenic factors. 4 The introduction of new therapeutic agents, such as immunomodulatory drugs (IMIDs), proteasome inhibitors (PI), and monoclonal antibodies in the treatment of multiple myeloma (MM), lead to increased survival rates. 5 However, several of these novel treatments are associated with an increased risk of infectious complications. 6 We recently reported that MM patients receiving daratumumab were at increased risk for bacterial and viral infections. 7 Pathogenesis of MM results in the suppression of the adaptive immune system and leads to low levels of immunoglobulin production. Reduction of immunoglobulin levels is seen in more than 70% of patients with MM. 8 Such immunoparesis (hypogammaglobulinemia) is correlated with shorter overall survival (OS) and progression-free survival (PFS). 9 such as the European Myeloma Network (EMN). 10 More studies are needed to define the risk groups among MM patients and to refine treatment recommendations. We therefore, here, assessed a cohort of patients that were previously diagnosed with MM or smoldering MM (SMM) and developed COVID-19 during March to May 2020 in Stockholm.

The characteristics of the nine patients followed are summarized in Table 1 . Of the patients, eight had MM and one patient had SMM.

Six of the MM patients were on daratumumab-based treatment and two of the patients were treated with lenalidomide-dexamethasone (RD). All patients presented with fever and eight out of nine patients additionally reported dry cough. Other symptoms were dyspnea, arthralgia, diarrhea, and ageusia (loss of taste). Upon symptom onset, the MM treatments were discontinued. All patients were confirmed with COVID-19 by PCR from nasopharyngeal swabs within 14 days after symptom debut. Four out of nine patients died within three weeks after initial symptoms ( 

Immunoparesis is associated with worse overall survival, which is not generally related to an increased risk of infections. 9 Abbreviations: CR, complete response; dD, (daratumumab-dexamethasone); dD-Veneto, (daratumumab-dexamethasone-venetoclax); dKD, (daratumumab-carfilzomib-dexamethasone); DM2, Diabetes mellitus type 2; dRD, (daratumumab-lenalidomide-dexamethasone); dVD, (daratumumab-bortezomib-dexamethasone); HDT, (high-dose treatment); HT, hypertension; KD, (carfilzomib-dexamethasone); KPD, (carfilzomibpomalidomide-dexamethasone); MR, minimal response; ND, not determined; NE, not evaluable due to exitus; PD, (pomalidomide-dexamethasone); PD, progressive disease; PR, partial response; RD, (lenalidomide-dexamethasone); VCD, (bortezomib-cyclophosphamide-dexamethasone); VGPR, very good partial response; VRD, (bortezomib-lenalidomide-dexamethasone); VTD, (bortezomib-thalidomide-dexamethasone). a As defined by the International Myeloma Working Group. 

Characteristics of and important lessons from the Coronavirus Disease 2019 (COVID-19) outbreak in China: Summary of a report of 72314 cases from the Chinese Center for Disease Control and Prevention

Risk factors of fatal outcome in hospitalized subjects with Coronavirus Disease 2019 from a nationwide analysis in China

Patients with cancer appear more vulnerable to SARS-COV-2: a multicenter study during the COVID-19 outbreak

COVID-19 and cancer: lessons from a pooled meta-analysis

Multiple myeloma epidemiology and survival: a unique malignancy

Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients

Infectious complications and NK cell depletion following daratumumab treatment of Multiple Myeloma

Preserved levels of uninvolved immunoglobulins are independently associated with favorable outcome in patients with symptomatic multiple myeloma

Characterisation of immunoparesis in newly diagnosed myeloma and its impact on progression-free and overall survival in both old and recent myeloma trials

Management of patients with multiple myeloma in the era of COVID-19 pandemic: a consensus paper from the European Myeloma Network (EMN)

Risk factors for infections in newly diagnosed multiple myeloma patients: a Danish retrospective nationwide cohort study

COVID-19 infections and outcomes in patients with multiple myeloma

A tertiary center experience of multiple myeloma patients with COVID-19: lessons learned and the path forward. medRxiv

Real-world assessment of the clinical impact of symptomatic infection with severe acute respiratory syndrome coronavirus (COVID-19 disease) in patients with multiple myeloma receiving systemic anti-cancer therapy