Management of systemic AL amyloidosis: recommendations of the Myeloma Foundation of Australia Medical and Scientific Advisory Group

Abstract

Systemic AL amyloidosis is a plasma cell dyscrasia with a characteristic clinical phenotype caused by multi‐organ deposition of an amyloidogenic monoclonal protein. This condition poses a unique management challenge due to the complexity of the clinical presentation and the narrow therapeutic window of available therapies. Improved appreciation of the need for risk stratification, standardised use of sensitive laboratory testing for monitoring disease response, vigilant supportive care and the availability of newer agents with more favourable toxicity profiles have contributed to the improvement in treatment‐related mortality and overall survival seen over the past decade. Nonetheless, with respect to the optimal management approach, there is a paucity of high‐level clinical evidence due to the rarity of the disease, and enrolment in clinical trials is still the preferred approach where available. This review will summarise the Clinical Practice Guidelines on the Management of Systemic Light Chain (AL) Amyloidosis recently prepared by the Medical Scientific Advisory Group of the Myeloma Foundation of Australia. It is hoped that these guidelines will assist clinicians in better understanding and optimising the management of this difficult disease.

Induction therapy pre‐autologous stem cell transplantation in immunoglobulin light chain amyloidosis: a retrospective evaluation

“…The arguments against induction for all patients with AL prior to ASCT consist of: first, there is a subgroup of patients with AL amyloidosis receiving 12 ASCT, approximately 43% of our ASCT population, who are very low risk. These patients have both low Mayo 2012 stage disease and BMPC ≤ 10%.…”

“…[11] Various factors affect survival outcomes and it is essential to have an appropriate selection criteria. Cardiac amyloidosis accounted for the majority of treatment related morality [12] Troponin T > 0.06 mcg/L and brain-type natriuretic peptide (BNP) > 300 pg/ml, associated with a poor survival outcome, are current recommendation as exclusion for transplant. [13,14] It is well recognized that AL patients who achieve the deepest hematological response following ASCT have a superior organ response and a longer overall survival (OS).…”

Epidemiology of AL amyloidosis: a real-world study using US claims data

“…As there is no diagnosis code specific to AL amyloidosis, the following algorithm, which was used in a previously published study, 16 was used to identify patients in each calendar year during the study period ( [17][18][19][20][21] for AL amyloidosis (bendamustine, bortezomib, carfilzomib, cyclophosphamide, dexamethasone, prednisone, doxycycline, lenalidomide, melphalan, pomalidomide, thalidomide, or hematopoietic stem cell transplant [HSCT]) on or after the first amyloidosis diagnosis in the study period. A similar population-identification algorithm was used in a recent publication and confirmed with clinical input.…”

Supportive Care in AL Amyloidosis

“…Non-dihydropyridine calcium channel blockers can cause bradycardia and have negative inotropic effects [27]. In this setting, the best tolerated option for rhythm control is amiodarone, also recommended by some authors for primary arrythmia prophylaxis at a dose of 200 mg/day in patients with high-risk features on Holter monitor testing such as ventricular couplets or non-sustained ventricular tachycardia [32]. However, there is no evidence based on controlled clinical trials supporting the use of prophylactic antiarrhythmic drugs [33].…”

“…The alpha-adrenergic agonist midodrine can be administered orally at an initial dose of 2.5 mg t.i.d. and progressively increased to a maximum dose of 10 mg t.i.d., taking care of potential adverse events such as supine hypertension and tachycardia [32]. In uncommon cases without concomitant nephrotic syndrome or amyloid cardiomyopathy, fludrocortisone (100–200 μg/day) or salt tablets can be used taking care to avoid supine hypertension.…”