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Blood Res 2022; 57(2):

Published online June 30, 2022

https://doi.org/10.5045/br.2022.2021227

© The Korean Society of Hematology

Multidisciplinary supportive care in systemic light chain amyloidosis

Bou Zerdan Maroun1, Sabine Allam2, Chakra P. Chaulagain1

1Department of Hematology-Oncology, Myeloma and Amyloidosis Program, Maroone Cancer Center, Cleveland Clinic Florida, Weston, FL, USA, 2Department of Medicine, Faculty of Medicine, University of Balamand, Beirut, Lebanon

Correspondence to : Chakra P. Chaulagain, M.D., FACP
Department of Hematology-Oncology, Myeloma and Amyloidosis Program, Maroone Cancer Center, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd, Weston, FL 33331, USA
E-mail: CHAULAC@ccf.org

Received: December 29, 2021; Revised: April 30, 2022; Accepted: May 4, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The immunoglobulin light-chain amyloidosis is a multisystemic disease which manifests by damage to the vital organs by light chain-derived amyloid fibril. Traditionally, the treatment has been directed to the underlying plasma cell clone with or without high dose chemotherapy followed by autologous stem cell transplantation using melphalan based conditioning. Now with the approval of highly tolerable anti-CD38 monoclonal antibody daratumumab based anti-plasma cell therapy in 2021, high rates of hematologic complete responses are possible even in patients who are otherwise deemed not a candidate for autologous stem cell transplantation. However, despite the progress, there remains a limitation in the strategies to improve symptoms particularly in patients with advanced cardiac involvement, those with nephrotic syndrome and autonomic dysfunction due to underlying systemic AL amyloidosis. The symptoms can be an ordeal for the patients and their caregivers and effective strategies are urgently needed to address them. The supportive care is aimed to counteract the symptoms of the disease and the effects of the treatment on involved organs’ function and preserve patients’ quality of life. Here we discuss multidisciplinary approach in a system-based fashion to address the symptom management in this dreadful disease. In addition to achieving excellent anti-plasma cell disease control, using treatment directed to remove amyloid from the vital organs can theoretically hasten recovery of the involved organs thereby improving symptoms at a faster pace. Ongoing phase III clinical trials of CAEL-101 and Birtamimab will address this question.

Keywords Supportive care, Multidisciplinary approach, Hematology, Amyloidosis, Light chain

Article

Review Article

Blood Res 2022; 57(2): 106-116

Published online June 30, 2022 https://doi.org/10.5045/br.2022.2021227

Copyright © The Korean Society of Hematology.

Multidisciplinary supportive care in systemic light chain amyloidosis

Bou Zerdan Maroun1, Sabine Allam2, Chakra P. Chaulagain1

1Department of Hematology-Oncology, Myeloma and Amyloidosis Program, Maroone Cancer Center, Cleveland Clinic Florida, Weston, FL, USA, 2Department of Medicine, Faculty of Medicine, University of Balamand, Beirut, Lebanon

Correspondence to:Chakra P. Chaulagain, M.D., FACP
Department of Hematology-Oncology, Myeloma and Amyloidosis Program, Maroone Cancer Center, Cleveland Clinic Florida, 2950 Cleveland Clinic Blvd, Weston, FL 33331, USA
E-mail: CHAULAC@ccf.org

Received: December 29, 2021; Revised: April 30, 2022; Accepted: May 4, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The immunoglobulin light-chain amyloidosis is a multisystemic disease which manifests by damage to the vital organs by light chain-derived amyloid fibril. Traditionally, the treatment has been directed to the underlying plasma cell clone with or without high dose chemotherapy followed by autologous stem cell transplantation using melphalan based conditioning. Now with the approval of highly tolerable anti-CD38 monoclonal antibody daratumumab based anti-plasma cell therapy in 2021, high rates of hematologic complete responses are possible even in patients who are otherwise deemed not a candidate for autologous stem cell transplantation. However, despite the progress, there remains a limitation in the strategies to improve symptoms particularly in patients with advanced cardiac involvement, those with nephrotic syndrome and autonomic dysfunction due to underlying systemic AL amyloidosis. The symptoms can be an ordeal for the patients and their caregivers and effective strategies are urgently needed to address them. The supportive care is aimed to counteract the symptoms of the disease and the effects of the treatment on involved organs’ function and preserve patients’ quality of life. Here we discuss multidisciplinary approach in a system-based fashion to address the symptom management in this dreadful disease. In addition to achieving excellent anti-plasma cell disease control, using treatment directed to remove amyloid from the vital organs can theoretically hasten recovery of the involved organs thereby improving symptoms at a faster pace. Ongoing phase III clinical trials of CAEL-101 and Birtamimab will address this question.

Keywords: Supportive care, Multidisciplinary approach, Hematology, Amyloidosis, Light chain

Fig 1.

Figure 1.Perivascular amyloid deposits demonstrated as apple green birefringence under polarized light in this Congo Red stain specimen from a patient with systemic AL amyloidosis due to lymphoplasmacytic lymphoma (Bone marrow Congo Red, ×20).
Blood Research 2022; 57: 106-116https://doi.org/10.5045/br.2022.2021227

Fig 2.

Figure 2.An electrocardiogram (EKG) showing pseudo-infarction pattern or Q-waves in chest Leads V1-V3 in this 62-year-old man presenting with AL cardiomyopathy from underlying clonal plasma cell neoplasms. Both limb and chest lead also demonstrate presence of low voltage.
Blood Research 2022; 57: 106-116https://doi.org/10.5045/br.2022.2021227

Fig 3.

Figure 3.One of the cutaneous manifestations of systemic AL amyloidosis include amyloid purpura. Amyloid purpura is non-blanching purpuric relapsing and remitting skin lesions usually involving the peri-orbital skin, the upper trunk and neck. The purpura can break and cause oozing, skin breakdown and significant pain. A marked thinning of skin and skin breakdown needing local care (for oozing and bleeding) is seen in the picture.
Blood Research 2022; 57: 106-116https://doi.org/10.5045/br.2022.2021227

Table 1 . Major clinical problems and suggested supportive care in systemic AL amyloidosis..

Clinical syndrome Intervention
Anasarca due to heart failure and/or nephrotic syndromeSalt restriction and diuretics are the mainstay of treatment, tracking daily weight, collaboration and co-management with cardio-oncology and nephron-oncology when available
Ventricular or supra-ventricular tachy-arrhythmiaAmiodarone is the mainstay of treatment, collaboration with cardiac electrophysiology for trans-catheter ablation and need for anticoagulation to prevent thrombo-embolic complications
Sick sinus syndrome and heart blocksPacemakers, AICD remains controversial
Nephrotic syndromeIn addition to fluid management, clinicians should pay attention to the risk of accelerated atherosclerosis due to hyperlipidemia, risk of VTE and infections
HypotensionElastic stockings, postural training (avoiding sudden change in positions), judicious use of midodrine in severe cases, use of fludrocortisoneif limited cardiac or renal involvement
Peripheral neuropathyGabapentin, pregabalin are mainstay of therapy, SSRI can be useful, amitriptyline and nortriptyline should be avoided due to anti-cholinergic side effects
MalnutritionAdequate calorie and protein intake is important, all patients should have a nutritional plan
ConstipationMetoclopramide can improve motility, stool softener both useful, osmotic laxatives e.g., milk of magnesium need to be avoided
DiarrheaLoperamide may be useful,
Organ transplantation1.Kidney transplantation for persistent ESRD or heart transplantation for refractory heart failure despite hematologic complete response
2.For young and otherwise fit patient with isolated severe cardiac involvement, heart transplant followed by chemotherapy or HSCT can be considered
Mental healthAnxiety and depression are common, routine screening with help of social worker or clinical psychologist is recommended.

Abbreviations: AICD, automatic implantable cardioverter defibrillator; ESRD, end stage renal disease; HSCT, autologous hematopoietic stem cell transplantation..


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