COVID-19 infection in patients with multiple myeloma: a German-Chinese experience from Würzburg and Wuhan

Currently, experience with COVID-19 in multiple myeloma (MM) is still very limited. Terefore, we conducted this analysis of MM patients infected by COVID-19 from two prominent hematology centers in Wuhan and Wurzburg (Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China and University Hospital of Wurzburg, Wurzburg, Germany) as of 9 June 2020. In total, we identifed fve Caucasian patients from Wurzburg and three Asian patients from Wuhan. The majority of the patients were male (n=5, 63%), and the median age at COVID-19 diagnosis was 57 (range 39-83 years). Tree patients had newly diagnosed (ND) MM, and two of them were therapy naive at diagnosis of COVID-19. One patient from Wuhan was receiving the second cycle of VTD (bortezomib, thalidomide, and dexamethasone) as the first line therapy. In Wuhan, a patient with extramedullary progression (No. 6) received leukapheresis to prepare for a salvage chimeric antigen receptor T-cell (CAR-T) therapy. Due to COVID-19 infection, systemic anti-MM treatment was discontinued in all eight patients. Notably, two patients in Wurzburg showed no COVID-19 symptoms, and the other three patients exhibited only mild symptoms such as fever, cough, and nausea, which did not require an intensive care unit (ICU) admission. Tree patients did not receive any COVID-19 treatment, and all fve patients in Wurzburg recovered. In contrast, two patients from Wuhan developed severe respiratory syndrome so that mechanical ventilation and circulatory support were needed. The patient who was receiving the frontline therapy with VTD also had an elevated procalcitonin value (30.05 ng/ml), suggesting an additional bacterial infection, and this patient died due to acute respiratory failure. In addition, two out of fve patients in our cohort did not show positive IgM or IgG for COVID-19 afer recovery. In summary, our observations showed that COVID-19 infection could be severe especially in NDMM, and also suggested inadequate humoral immune response in MM patients, probably due to secondary immune defciency caused by the treatments or the disease itself. Surprisingly, the MM patients in Wurzburg did not present any signs of severe COVID-19 infection. Other than Wuhan where COVID-19 was reported for the first time, in Europe, the pandemic had already been announced, and in Germany the lock-down came relatively early in comparison to other countries.


Dear Editor,
The Chinese colleagues from Wuhan reported for the first time the novel coronavirus (COVID-19), which caused severe acute respiratory syndrome [1]. Currently, COVID-19 continues to spread worldwide and is affecting all fields of health care including patients with malignant diseases. The plasma cell neoplasm multiple myeloma (MM) represents the second most common hematological malignancy in adults, which is characterized by secondary immune dysfunction and usually causes infectious complications, especially of the respiratory tract [2][3][4]. At present, there are only few reports on COVID-19 infection in patients with hematological malignancies including MM, from China, the USA, and the UK [5][6][7][8]. Generally, experience with COVID-19 in MM is still very limited, and there may be regional differences in disease severity. Therefore, we conducted this study of MM patients infected by COVID-19 and compared the clinical features of patients from Germany and China.
We retrieved and analyzed the data of MM patients with laboratory confirmed COVID-19 infection at two prominent hematology centers in Wuhan and Würzburg (Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, and University Hospital of Würzburg, Würzburg, Germany) as of 9 June 2020. This study was performed in accordance with the Declaration of Helsinki as revised in 2013 and with national ethical standards at both centers.
We summarized patients' characteristics, treatment, and outcome in Table 1. In total, we identified five Caucasian patients from Würzburg (Nos. [1][2][3][4][5] and three Asian patients from Wuhan (Nos. [6][7][8]. The majority of the patients were male (n = 5, 63%), and the median age at COVID-19 diagnosis was 57 (range 39-83 years). Only one patient (No. 2) presented high-risk cytogenetics, i.e., t(4;14). Three patients (Nos. 5, 7, and 8) had newly diagnosed (ND) MM, and two of them (Nos. 5 and 8) were therapy naïve at diagnosis of COVID-19. One patient (No. 7) from Wuhan was receiving the second cycle of VTD (bortezomib, thalidomide, and dexamethasone) as frontline therapy. High-dose melphalan with autologous stem cell transplant (SCT) was performed in three patients (Nos. 1-3), all from Würzburg. At the time point of COVID-19 diagnosis, three patients (Nos. 1, 3, and 4) were treated with daratumumab-containing regimens. In Wuhan, a patient with extramedullary progression (No. 6) received leukapheresis to prepare for a salvage chimeric antigen receptor T-cell (CAR-T) therapy, and this patient was hospitalized in the hematology department until 31 January 2020. The three patients from Wuhan were infected by COVID-19 in January or February 2020, while the Würzburg patients were diagnosed in March or April 2020. Due to COVID-19 infection, anti-MM treatment was discontinued in all the patients. Notably, two patients (Nos. [3][4] in Würzburg showed no COVID-19 symptoms, and the other three patients (Nos. 1, 2, and 5) exhibited only mild symptoms such as fever, cough, and nausea, which did not require an intensive care unit (ICU) admission. Three patients (Nos. 2, 3, and 5) did not receive any COVID-19 treatment, and all five patients in Würzburg recovered. In contrast, two patients (Nos. 6-7) from Wuhan developed severe respiratory syndrome, so mechanical ventilation and circulatory support were needed. The patient No. 7 who was receiving the frontline therapy with VTD also had an elevated procalcitonin value (30.05 ng/ml), suggesting an    [5]. Additionally, a study from the USA demonstrated the severity and high mortality of COVID-19 infection in MM patients, especially in African American [8]. In another larger study from the UK, the mortality for COVID-19 was even as high as 54.6% (41/75) in MM patients, which was significantly higher than the general population [7]. Importantly, both studies suggested that patients with NDMM had a higher mortality rate, which might be related with MM-induced immune suppression and risk of infection caused by bacteria, fungi, and other viruses [7,8]. A lower risk for developing hyperinflammatory immune responses in late-stage patients might be an alternative explanation. Dufour et al. recently reported the experience from Belgium in this Journal (published on 23 June 2020), which also demonstrated a high mortality of 35% caused by COVID-19 infection in MM patients, and patients with immigration background especially North-Africans showed the worst survival outcome. However, the majority of the patients who passed away (5/7, 71%) had progressive MM at COVID-19 [9]. In our cohort, the only patient who died was a patient with NDMM receiving frontline therapy, and she showed signs of additional bacterial infection. Surprisingly, the MM patients in Würzburg did not present any signs of severe COVID-19 infection. Other than Wuhan where COVID-19 was reported for the first time, the pandemic had been announced in Europe, and in Germany, the lockdown came relatively early in comparison with the other countries. In addition, as two out of five patients in our cohort did not show positive IgM or IgG for COVID-19 after recovery, the role of serologic test to identify asymptomatic cases in MM should be further evaluated. Currently, the COVID-19 pandemic worldwide is still not under control, and there is still no causal treatment or vaccine for COVID-19, so we probably have to face this virus for longer time than expected. Strategies such as rational local organization, local disinfection, and hygiene maintenance, training of health workers and patients represent important steps to prevent nosocomial infection, which are also applicable for the time after the pandemic [10]. Importantly, MM patients with COVID-19 infection need close monitoring for severe COVID-19-related complications, and early intervention may be life-saving for the patients [11].
Funding Information Open Access funding provided by Projekt DEAL.

Compliance with ethical standards
Conflicts of interest All authors declare that they have no conflicts of interest relevant to the submitted manuscript.
Statement of informed consent Informed consent was obtained from all patients for being included in the study.
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