Challenges in the management of patients with systemic light chain (AL) amyloidosis during the COVID‐19 pandemic

Abstract

Summary The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐associated coronavirus disease 2019 (COVID‐19) is primarily manifested as a respiratory tract infection, but may affect and cause complications in multiple organ systems (cardiovascular, gastrointestinal, kidneys, haematopoietic and immune systems), while no proven specific therapy exists. The challenges associated with COVID‐19 are even greater for patients with light chain (AL) amyloidosis, a rare multisystemic disease affecting the heart, kidneys, liver, gastrointestinal and nervous system. Patients with AL amyloidosis may need to receive chemotherapy, which probably increases infection risk. Management of COVID‐19 may be particularly challenging in patients with AL amyloidosis, who often present with cardiac dysfunction, nephrotic syndrome, neuropathy, low blood pressure and gastrointestinal symptoms. In addition, patients with AL amyloidosis may be more susceptible to toxicities of drugs used to manage COVID‐19. Access to health care may be difficult or limited, diagnosis of AL amyloidosis may be delayed with detrimental consequences and treatment administration may need modification. Both patients and treating physicians need to adapt in a new reality.

Potential ‘significance’ of monoclonal gammopathy of ‘undetermined significance’ during COVID-19 pandemic

“… IMiDs (lenalidomide and pomalidomide) are potentially myelosuppressive and prothrombotic Avoid use of lenalidomide and pomalidomide, particularly in MGRS during COVID-19 pandemic Ixazomib: Oral administration, and its potential anti-SARS-CoV-2 properties are particularly desirable during COVID-19 pandemic # 31 Ixazomib may be preferred over bortezomib for patients with newly diagnosed AL amyloidosis, or RR cases ## Consider Ixazomib instead of Bortezomib for maintenance ### Purine analogues like Bendamustine, cladribine, and fludarabine cause prolonged lymphopenia Avoid these drugs as chemotherapy backbone with Rituximab $ Alkylators (chlorambucil, cyclophosphamide) may be used as chemotherapy backbone with Rituximab $$ Rituximab can cause hypogammaglobulinemia, and prolonged B-cell depletion [ 28 ]. IV Rituximab administration is prolonged, and needs hospital visits Maintenance Rituximab may either be omitted, or increased in frequency from 2-monthly to 3-monthly infusions $$$ Consider SC Rituximab wherever available to reduce hospital visits Autologous HSCT causes profound and prolonged immunosuppression [ 24 ] Both autologous HSCT, and renal transplant must be delayed for patients with MGRS, atleast till the COVID-19 pandemic is reasonably controlled Treatment of MGCS in patients with COVID-19 Immunosuppressive medications [ 19 ] PI, IMiDs, corticosteroids, DARA, alkylators, and Rituximab are potentially immunosuppressive Withhold all the immunosuppressive therapies at the first diagnosis of COVID-19 Resume treatment of MGCS later, once the patient recovers fully from COVID-19 General measures Risk of worsening cardiac, and renal function with COVID-19 in MGRS Treatment of MGCS must be supportive Meticulous monitoring of fluid, and electrolyte balance for MGRS patients Treatment of COVID-19 in patients with MGCS Anti-COVID-19 drugs [ 19 , 33 ] Remdesivir, Lopinavir/Ritonavir, Favipiravir, and dexamethasone have shown some efficacy Cardiotoxic- Remdesivir, Lopinavir/Ritonavir Nephrotoxic- Remdesivir These drugs may be cautiously used to treat COVID-19 in ...…”

“…Patients with AL amyloidosis have vascular friability, and haemostatic abnormalities which could predispose them to bleeding [ 19 ]…”

“…Cardio-renal involvement is most characteristic for immunoglobulin light-chain (AL) amyloidosis, and monoclonal immunoglobulin deposition disease (MIDD) [ 18 ]. Although, COVID-19 is predominantly a respiratory illness, involvement of cardiac, gastrointestinal, kidneys, central nervous system (CNS), skin, and hemato-immune systems have been recognised [ 19 ]. COVID-19-related myocarditis may cause elevation of biomarkers of cardiac injury like troponins, and N-terminal pro-brain natriuretic peptide (NT-Pro-BNP).…”

“…COVID-19-related myocarditis may cause elevation of biomarkers of cardiac injury like troponins, and N-terminal pro-brain natriuretic peptide (NT-Pro-BNP). AKI has been reported in about 0.5%–25% COVID-19 patients, and about 43.9% of such cases may have proteinuria [ 19 ]. Such a multisystem involvement in COVID-19 could pose several diagnostic, and therapeutic challenges for patients with MGCS.…”

“…Due to its potential organ threatening nature, diagnostic work-up for MGRS as recommended even during COVID-19 pandemic [ 18 ]. Organ-directed biopsy may be compromised during the COVID-19 pandemic due to limited availability of health-care resources for performing the invasive procedures, or reluctance of the patients to seek medical attention due to the fear of COVID-19 [ 19 ]. Lesser invasive sites of tissue sampling like abdominal fat pad, or gingival biopsies may be considered for AL amyloidosis, although a negative result from these sites does not necessarily exclude the diagnosis [ 18 ].…”