What are the guideline sources, guidelines and references for Immunoglobulin light chain amyloidosis ?
Guideline sources The following summarized guidelines for the evaluation and management of immunoglobulin light chain amyloidosis are prepared by our editorial team based on guidelines from the International Society of Amyloidosis (ISA/EHA 2023; 2022), the Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART 2021), the American College of Radiology (ACR 2021), and the British Committee for Standards In Haematology (BCSH 2015). 1 2 3 4 5 6 Guidelines 1. Screening and diagnosis https://web.pathway.md/diseases/recx3f97oJg0I2mpW 1/8 6/24/23, 2:28 PM Immunoglobulin light chain amyloidosis Pathway Clinical presentation: recognize that AL amyloidosis is a disease with insidious onset and considerable clinical heterogeneity and high level of clinical suspicion is essential to avoid delayed diagnosis. B 2. Diagnostic investigations Laboratory tests: obtain comprehensive assessment of the extent of organ involvement and dysfunction using noninvasive criteria, including obtaining serum amyloid P component scanning when feasible. B Show 2 more Cardiac imaging: As per ACR 2021 guidelines, obtain resting TTE as first-line imaging to detect infiltrative disease and assess diastolic function, or cardiac MRI without and with IV contrast for tissue characterization and risk stratification as the initial imaging of patients with suspected restrictive cardiomyopathy or infiltrative disease when ischemic cardiomyopathy has already been excluded. B As per BCSH 2015 guidelines, obtain echocardiography (cardiac MRI) to assess amyloid involvement, recognizing that because of the rarity of the condition, involvement may go unrecognized or not be adequately assessed. B Nerve conduction studies: obtain nerve conduction studies and autonomic function tests in patients with suspected neuropathy. B 3. Diagnostic procedures Biopsy and pathology: perform biopsy of an apparently affected organ, if possible, for histological diagnosis in patients with suspected AL amyloidosis. B Show 7 more 4. Medical management General principles: As per mSMART 2021 guidelines, initiate treatment immediately in virtually all patients with systemic AL amyloidosis. B Show 5 more As per BCSH 2015 guidelines, treat patients with AL amyloidosis in designated regional amyloidosis treatment centers, where possible, with on-site availability of multidisciplinary care with interest and experience in managing patients with amyloidosis. Show 3 more Goals of treatment: As per EHA 2023 guidelines: https://web.pathway.md/diseases/recx3f97oJg0I2mpW 2/8 6/24/23, 2:28 PM Immunoglobulin light chain amyloidosis Pathway Set complete hematologic response, (Grade B, Level IIb) with involved free light chain < 20 mg/L or a difference between the involved and uninvolved light chains < 10 mg/L, as the goal of treatment. B Consider modifying treatment in patients achieving less than a very good partial response by cycle 3 or less than a partial response by cycle 2. C As per mSMART 2021 guidelines: Set hematologic very good partial response or better as the goal of treatment. B Recognize that the ideal goal is the hematologic complete response, but weigh it against the toxicity of therapy and lack of specificity and sensitivity of assays. B Set improvement in organ function, preferably to near-normal value, as the preferred organ response goal. B First-line regimens: As per mSMART 2021 guidelines, offer daratumumab in combination with bortezomib, cyclophosphamide, and dexamethasone as the standard of care in transplant-ineligible patients with newly diagnosed AL amyloidosis. A Show 2 more As per BCSH 2015 guidelines, offer combination chemotherapy regimens similar to regimens used in myeloma but typically using dexamethasone as first-line therapy in patients with AL amyloidosis. Prefer proteasome inhibitor-based regimens for better response rates and outcomes and a bortezomib-alkylator-steroid combination when a rapid response is desirable (cardiac involvement, renal impairment, severe hypoalbuminemia, fluid retention). B Show 11 more Management of cardiac involvement, chemotherapy: As per ISA/EHA 2023 guidelines: Offer daratumumab, cyclophosphamide, bortezomib, and dexamethasone as first-line therapy in patients with cardiac stage I-IIIa. A Offer cyclophosphamide, bortezomib, and dexamethasone B or velcade, melphalan, and dexamethasone as alternatives. A Offer dose-modified daratumumab, cyclophosphamide, bortezomib, and dexamethasone B or single-agent daratumumab B in patients with cardiac stage IIIb. Offer dose-modified cyclophosphamide, bortezomib, and dexamethasone or velcade, melphalan, and dexamethasone as alternatives. B As per mSMART 2021 guidelines, consider offering bortezomib at lower initial doses (0.7-1.0 mg/m ) in patients with advanced cardiac disease. C As per BCSH 2015 guidelines: Offer lower doses of bortezomib with consideration for inpatient continuous cardiac monitoring initially and a view to dose escalation if tolerated in patients with advanced stage III cardiac disease. B Be cautious when using thalidomide in patients with stage III cardiac disease. B Management of renal involvement: As per mSMART 2021 guidelines: https://web.pathway.md/diseases/recx3f97oJg0I2mpW 3/8 6/24/23, 2:28 PM Immunoglobulin light chain amyloidosis Pathway Administer diuretics as the mainstay of management of volume overload due to nephrotic syndrome or therapy. B Consider modifying drug doses in patients on hemodialysis. C As per BCSH 2015 guidelines, consider performing dialysis in patients with end-stage renal failure without associated severe HF. B Management of peripheral nerve involvement: As per EHA 2023 guidelines, consider offering any of the following regimens in patients with AL amyloidosis with neuropathy: single-agent daratumumab (preferred) lenalidomide, dexamethasone melphalan, dexamethasone carfilzomib, dexamethasone venetoclax. C As per mSMART 2021 guidelines: Consider offering a trial of drugs used to treat symptoms of small fiber neuropathy in patients with peripheral nerve involvement. C Avoid using bortezomib in patients with neuropathy. D As per BCSH 2015 guidelines: Offer lenalidomide as one of the preferred treatment regimens in patients with AL amyloidosis with significant peripheral neuropathy. B Avoid using neurotoxic drugs (thalidomide and bortezomib) in patients with grade III-IV neuropathy. D Management of autonomic dysfunction: As per mSMART 2021 guidelines, consider administering midodrine, droxidopa, and pyridostigmine for the management of orthostasis related to autonomic dysfunction. C As per BCSH 2015 guidelines: Consider offering support stockings in combination with modest doses of fludrocortisone in selected patients with orthostatic hypotension. B Administer midodrine as the most effective drug for orthostatic hypotension in patients with amyloidosis, recognizing that it can cause supine hypertension. B Management of bleeding: Initiate conventional supportive therapy (factor replacement, platelet transfusion, and antifibrinolytic agents) for the management of bleeding in patients with AL amyloidosis. B Consider administering factor X, if available, in patients with proven factor X deficiency. C Management of cardiac involvement, supportive therapy: As per mSMART 2021 guidelines: Administer diuretics as the mainstay of management of volume overload due to congestive HF or therapy. B https://web.pathway.md/diseases/recx3f97oJg0I2mpW 4/8 6/24/23, 2:28 PM Immunoglobulin light chain amyloidosis Pathway Be cautious when using -blockers, ACEIs, ARBs, and CCBs in patients with cardiac amyloidosis. B As per BCSH 2015 guidelines, consider obtaining a 24-hour ECG monitoring after diagnosis. B Show 2 more Maintenance and consolidation therapy: As per EHA 2023 guidelines: Do not offer routine maintenance or consolidation therapy in patients with AL amyloidosis. D Consider offering consolidation therapy in patients with a very good partial or complete response with persistent minimal residual disease and no organ response. C As per EHA 2022 guidelines, do not offer consolidation or maintenance therapy routinely after stem cell transplantation in patients with AL amyloidosis. D As per mSMART 2021 guidelines: Consider offering maintenance therapy after induction therapy in patients with concomitant symptomatic multiple myeloma or high-risk FISH abnormalities. C Consider offering maintenance therapy after ASCT in patients with myeloma phenotype or high-risk FISH abnormalities. C As per BCSH 2015 guidelines, insufficient evidence to support the use of maintenance or consolidation therapies outside the context of a clinical trial. I 5. Nonpharmacologic interventions Nutrition: Offer nutritional supplementation in patients with gastrointestinal symptoms. B Consider administering TPN if gastrointestinal symptoms are disabling, and the patient becomes malnourished. C 6. Therapeutic procedures Autologous stem cell transplantation: As per mSMART 2021 guidelines, consider administering high-dose chemotherapy with ASCT in selected patients with AL amyloidosis. C Show 7 more As per BCSH 2015 guidelines, consider administering high-dose melphalan with ASCT without prior induction chemotherapy in patients with low level bone marrow plasma cell infiltration. Show 5 more Allogenic stem cell transplantation: Do not perform reduced intensity allogeneic transplantation as an upfront treatment due to the high treatment-related mortality. D https://web.pathway.md/diseases/recx3f97oJg0I2mpW 5/8 6/24/23, 2:28 PM Immunoglobulin light chain amyloidosis Pathway Consider performing reduced intensity allogeneic transplantation following relapse in selected fitter younger patients with limited organ involvement having a matched sibling donor. B 7. Surgical interventions Solid organ transplantation: As per mSMART 2021 guidelines, consider performing heart transplantation in very selected patients with AL amyloidosis. C Show 2 more As per BCSH 2015 guidelines, consider performing renal transplantation in selected patients with good performance status with little clinically significant extrarenal amyloid and if a clonal remission has been achieved. B Show 2 more 8. Specific circumstances Patients with immunoglobulin M-related amyloidosis: Offer rituximab and bendamustine or ASCT as first-line therapy in patients with IgM-related amyloidosis. B Offer the following regimens as alternative therapies in patients with IgM-related amyloidosis: rituximab, bortezomib, and dexamethasone rituximab, cyclophosphamide, and dexamethasone cyclophosphamide, bortezomib, dexamethasone ibrutinib with or without rituximab. B Patients with t(11;14) translocation: Offer any of the following regimens in patients with t11;14 translocation: venetoclax B venetoclax, bortezomib, and dexamethasone B melphalan, dexamethasone. B Patients with localized amyloidosis: As per EHA 2023 guidelines: Offer local treatment (surgical, laser, or cytotherapeutic debulking) in patients with localized AL amyloidosis. B Avoid offering chemotherapy in patients with localized AL amyloidosis. Do not offer antifebrile antibodies outside of clinical trials. As per BCSH 2015 guidelines, consider performing local resection for the treatment of patients with localized AL amyloidosis. As per BCSH 2015 guidelines, consider offering radiotherapy in selected patients with localized AL amyloidosis. B https://web.pathway.md/diseases/recx3f97oJg0I2mpW 6/8 6/24/23, 2:28 PM Immunoglobulin light chain amyloidosis Pathway 9. Patient education General counseling: provide appropriate information and support in patients, their families and carers as an essential component of management. Show 7 more 10. Preventative measures Thromboprophylaxis: Consider administering prophylactic LMWH in patients high risk of VTE. C Consider administering aspirin in patients at low risk of VTE. C Prophylactic antibiotics: consider administering doxycycline as the prophylactic antibiotic of choice. C 11. Follow-up and surveillance Monitoring of treatment response: obtain free light chains or M-protein for monitoring of treatment response after each cycle of chemotherapy during treatment and every 1-3 months thereafter. B Show 2 more Management of relapsed/refractory disease: As per EHA 2023 guidelines, offer the following regimens in proteasome inhibitor-na ve patients or patients with prolonged response to first-line proteasome inhibitors: cyclophosphamide, bortezomib, and dexamethasone B velcade, melphalan, and dexamethasone B ixazomib, dexamethasone B daratumumab, velcade, cyclophosphamide, and dexamethasone. B Show 3 more As per mSMART 2021 guidelines, proceed with relapsed/refractory management algorithm for patients not achieving hematologic very good partial response (and for some not achieving hematologic complete response). B Show 5 more As per BCSH 2015 guidelines, recognize that there is no standard treatment for relapse. B Show 3 more References 1. Ashutosh D Wechalekar, Julian D Gillmore, Jenny Bird et al. Guidelines on the management of AL amyloidosis. Br J Haematol. 2015 Jan;168 2 186 206. Open https://web.pathway.md/diseases/recx3f97oJg0I2mpW 7/8 6/24/23, 2:28 PM Immunoglobulin light chain amyloidosis Pathway 2. Eli Muchtar, Angela Dispenzieri, Morie A Gertz et al. Treatment of AL Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART Consensus Statement 2020 Update. Mayo Clin Proc. 2021 Jun;96 6 1546 1577. Open 3. Ashutosh D Wechalekar, M Teresa Cibeira, Simon D Gibbs et al. Guidelines for non-transplant chemotherapy for treatment of systemic AL amyloidosis: EHA ISA working group. Amyloid. 2023 Mar;30 1 3 17. Open 4. Julian D Gillmore, Ashutosh Wechalekar, Jenny Bird et al. Guidelines on the diagnosis and investigation of AL amyloidosis. Br J Haematol. 2015 Jan;168 2 207 18. Open 5. Vaishali Sanchorawala, Mario Boccadoro, Morie Gertz et al. Guidelines for high dose chemotherapy and stem cell transplantation for systemic AL amyloidosis: EHA ISA working group guidelines. Amyloid. 2022 Mar;29 1 1 7. Open 6. Expert Panel on Cardiac Imaging, Prabhakar Rajiah, Jacobo Kirsch et al. ACR Appropriateness Criteria Nonischemic Myocardial Disease with Clinical Manifestations Ischemic Cardiomyopathy Already Excluded). J Am Coll Radiol. 2021 May;18 5S S83 S105. Open 7. Dispenzieri A, Buadi F, Kumar SK et al. Treatment of Immunoglobulin Light Chain Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART Consensus Statement. Mayo Clin Proc. 2015 Aug;90 8 1054 81. Open 8. Tiffany P Quock, Tingjian Yan, Eunice Chang et al. Epidemiology of AL amyloidosis: a real-world study using US claims data. Blood Adv. 2018 May 22;2 10 1046 1053. Open 9. Morie A Gertz. Immunoglobulin light chain amyloidosis: 2020 update on diagnosis, prognosis, and treatment. Am J Hematol. 2020 Jul;95 7 848 860. Open 10. Giampaolo Merlini, Angela Dispenzieri, Vaishali Sanchorawala et al. Systemic immunoglobulin light chain amyloidosis. Nat Rev Dis Primers. 2018 Oct 25;4 1 38. Open https://web.pathway.md/diseases/recx3f97oJg0I2mpW 8/8