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

Patients with multiple myeloma (MM) seem to be at increased risk for more severe COVID-19 infection and associated complications due to their immunocompromised state, the older age and comorbidities. The European Myeloma Network has provided an expert consensus statement in order to guide therapeutic decisions in the era of the COVID-19 pandemic. Patient education for personal hygiene and social distancing measures, along with treatment individualization, telemedicine and continuous surveillance for early diagnosis of COVID-19 are essential. In countries or local communities where COVID-19 infection is widely spread, MM patients should have a PCR test of nasopharyngeal swab for SARS-CoV-2 before hospital admission, starting a new treatment line, cell apheresis or ASCT in order to avoid ward or community spread and infections. Oral agent-based regimens should be considered, especially for the elderly and frail patients with standard risk disease, whereas de-intensified regimens for dexamethasone, bortezomib, carfilzomib and daratumumab should be used based on patient risk and response. Treatment initiation should not be postponed for patients with end organ damage, myeloma emergencies and aggressive relapses. Autologous (and especially allogeneic) transplantation should be delayed and extended induction should be administered, especially in standard risk patients and those with adequate MM response to induction. Watchful waiting should be considered for standard risk relapsed patients with low tumor burden, and slow biochemical relapses. The conduction of clinical trials should continue with appropriate adaptations to the current circumstances. Patients with MM and symptomatic COVID-19 disease should interrupt anti-myeloma treatment until recovery. For patients with positive PCR test for SARS-CoV-2, but with no symptoms for COVID-19, a 14-day quarantine should be considered if myeloma-related events allow the delay of treatment. The need for surveillance for drug interactions due to polypharmacy is highlighted. The participation in international COVID-19 cancer registries is greatly encouraged.

[1]  G. Doherty,et al.  Recommendations from national regulatory agencies for ongoing cancer trials during the COVID-19 pandemic , 2020, The Lancet Oncology.

[2]  Ruchong Chen,et al.  Cancer patients in SARS-CoV-2 infection: a nationwide analysis in China , 2020, The Lancet Oncology.

[3]  M. Dimopoulos,et al.  The role of cement augmentation with percutaneous vertebroplasty and balloon kyphoplasty for the treatment of vertebral compression fractures in multiple myeloma: a consensus statement from the International Myeloma Working Group (IMWG) , 2019, Blood Cancer Journal.

[4]  C. Hofmeister,et al.  Ninety-minute daratumumab infusion is safe in multiple myeloma , 2017, Leukemia.

[5]  J. Willan,et al.  Care of haematology patients in a COVID‐19 epidemic , 2020, British journal of haematology.

[6]  M. Boccadoro,et al.  Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. , 2012, Blood.

[7]  G. Barosi,et al.  Management of infectious complications in multiple myeloma patients: Expert panel consensus-based recommendations. , 2019, Blood reviews.

[8]  Per Block,et al.  Demographic science aids in understanding the spread and fatality rates of COVID-19 , 2020, Proceedings of the National Academy of Sciences.

[9]  D. Dingli,et al.  Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria , 2018, Blood Cancer Journal.

[10]  F. M. Stewart,et al.  Managing Cancer Care During the COVID-19 Pandemic: Agility and Collaboration Toward a Common Goal. , 2020, Journal of the National Comprehensive Cancer Network : JNCCN.

[11]  N. Munshi,et al.  Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma , 2017, The New England journal of medicine.

[12]  M. Santillana,et al.  Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multicenter Study during the COVID-19 Outbreak , 2020, Cancer discovery.

[13]  S. Rajkumar,et al.  Multiple myeloma: 2020 update on diagnosis, risk‐stratification and management , 2020, American journal of hematology.

[14]  C. Wang,et al.  Clinical characteristics of COVID-19-infected cancer patients: a retrospective case study in three hospitals within Wuhan, China , 2020, Annals of Oncology.

[15]  M. Dimopoulos,et al.  Myeloma bone disease: from biology findings to treatment approaches. , 2019, Blood.

[16]  J. Laubach,et al.  Subcutaneous versus intravenous daratumumab in patients with relapsed or refractory multiple myeloma (COLUMBA): a multicentre, open-label, non-inferiority, randomised, phase 3 trial. , 2020, The Lancet. Haematology.

[17]  S. Merler,et al.  Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy. , 2020, JAMA.

[18]  F. Puglisi,et al.  Managing COVID-19 in the oncology clinic and avoiding the distraction effect , 2020, Annals of Oncology.

[19]  A. Vangsted,et al.  Risk factors for infections in newly diagnosed Multiple Myeloma patients: A Danish retrospective nationwide cohort study , 2018, European journal of haematology.

[20]  M. Santillana,et al.  Patients with Cancer Appear More Vulnerable to SARS-CoV-2: A Multi-Center Study During the COVID-19 Outbreak , 2020 .

[21]  A. Oriol,et al.  Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplantation in multiple myeloma. , 2019, Blood.

[22]  R. Wäsch,et al.  Structured assessment of frailty in multiple myeloma as a paradigm of individualized treatment algorithms in cancer patients at advanced age , 2020, Haematologica.

[23]  M. Dimopoulos,et al.  Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma. , 2019, The New England journal of medicine.

[24]  M. Beksac,et al.  Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study , 2019, The Lancet.

[25]  M. Boccadoro,et al.  Early mortality in myeloma patients treated with first-generation novel agents thalidomide, lenalidomide, bortezomib at diagnosis: A pooled analysis. , 2018, Critical reviews in oncology/hematology.

[26]  D. Hesselink,et al.  Pharmacologic Treatment of Transplant Recipients Infected With SARS-CoV-2: Considerations Regarding Therapeutic Drug Monitoring and Drug–Drug Interactions , 2020, Therapeutic drug monitoring.

[27]  G. Gahrton,et al.  Infectious complications and NK cell depletion following daratumumab treatment of Multiple Myeloma , 2019, PloS one.

[28]  W. Liang,et al.  Risk Factors of Fatal Outcome in Hospitalized Subjects With Coronavirus Disease 2019 From a Nationwide Analysis in China , 2020, Chest.

[29]  J. Burke,et al.  Daratumumab, bortezomib, cyclophosphamide and dexamethasone in newly diagnosed and relapsed multiple myeloma: LYRA study , 2019, British Journal of Haematology.

[30]  M. Drayson,et al.  Levofloxacin prophylaxis in patients with newly diagnosed myeloma (TEAMM): a multicentre, double-blind, placebo-controlled, randomised, phase 3 trial , 2019, The Lancet. Oncology.

[31]  K. Anderson,et al.  Targeting CD38 Suppresses Induction and Function of T Regulatory Cells to Mitigate Immunosuppression in Multiple Myeloma , 2017, Clinical Cancer Research.

[32]  M. Gavriatopoulou,et al.  Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools , 2020, Cancers.

[33]  Michael D. Robbins,et al.  Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma , 2018, The New England journal of medicine.

[34]  H. Goldschmidt,et al.  Cardiovascular adverse events in modern myeloma therapy – Incidence and risks. A review from the European Myeloma Network (EMN) and Italian Society of Arterial Hypertension (SIIA) , 2018, Haematologica.

[35]  Marcus Groettrup,et al.  The Proteasome Inhibitor Bortezomib Enhances the Susceptibility to Viral Infection1 , 2009, The Journal of Immunology.

[36]  T. Mitsudomi,et al.  Testing for COVID-19 in lung cancer patients , 2020, Annals of Oncology.

[37]  D. Roden,et al.  Considerations for Drug Interactions on QTc in Exploratory COVID-19 (Coronavirus Disease 2019) Treatment. , 2020, Circulation.

[38]  Hui Guo,et al.  First case of COVID-19 in a patient with multiple myeloma successfully treated with tocilizumab , 2020, Blood Advances.

[39]  M. Pellegrini,et al.  Changing treatment paradigms for patients with plasma cell myeloma: impact upon immune determinants of infection. , 2014, Blood reviews.

[40]  K. Anderson,et al.  Bone Marker–Directed Dosing of Zoledronic Acid for the Prevention of Skeletal Complications in Patients with Multiple Myeloma: Results of the Z-MARK Study , 2015, Clinical Cancer Research.

[41]  Theodora Psaltopoulou,et al.  Hematological findings and complications of COVID‐19 , 2020, American journal of hematology.

[42]  P. Sonneveld,et al.  Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study , 2019, The Lancet.

[43]  Hans Erik Johnsen,et al.  International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. , 2014, The Lancet. Oncology.

[44]  Yongfeng Zhao,et al.  Immunomodulatory drugs and the risk of serious infection in multiple myeloma: systematic review and meta-analysis of randomized and observational studies , 2018, Annals of Hematology.

[45]  U. Mellqvist,et al.  Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients , 2015, Haematologica.

[46]  Zunyou Wu,et al.  Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. , 2020, JAMA.

[47]  F. Prósper,et al.  Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. , 2013, The New England journal of medicine.

[48]  M. Dimopoulos,et al.  Multiple myeloma: Role of autologous transplantation. , 2019, Cancer treatment reviews.

[49]  S. Lonial,et al.  Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. , 2019, The Lancet. Oncology.

[50]  A. Desai,et al.  COVID-19 and Cancer: Lessons From a Pooled Meta-Analysis. , 2020, JCO global oncology.

[51]  A. Vangsted,et al.  Causes of early death in multiple myeloma patients who are ineligible for high‐dose therapy with hematopoietic stem cell support: A study based on the nationwide Danish Myeloma Database , 2015, American journal of hematology.

[52]  Nathaniel Hupert,et al.  Clinical Characteristics of Covid-19 in New York City , 2020, The New England journal of medicine.

[53]  L. Pagano,et al.  Frequently asked questions regarding SARS-CoV-2 in cancer patients—recommendations for clinicians caring for patients with malignant diseases , 2020, Leukemia.

[54]  R. Fonseca,et al.  Randomized Trial of Lenalidomide Versus Observation in Smoldering Multiple Myeloma. , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[55]  D. Roden,et al.  Considerations for Drug Interactions on QTc Interval in Exploratory COVID-19 Treatment , 2020, Journal of the American College of Cardiology.

[56]  S. Bringhen,et al.  Caring for older adults with multiple myeloma during the COVID-19 Pandemic: Perspective from the International Forum for Optimizing Care of Older Adults with Myeloma , 2020, Journal of Geriatric Oncology.

[57]  G. Morgan,et al.  Expert panel consensus statement on the optimal use of pomalidomide in relapsed and refractory multiple myeloma , 2014, Leukemia.

[58]  M. Beksac,et al.  European Myeloma Network Guidelines for the Management of Multiple Myeloma-related Complications , 2015, Haematologica.

[59]  G. Morgan,et al.  International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.