Emerging Therapeutics for the Treatment of Light Chain and Transthyretin Amyloidosis

Abstract

Highlights Cardiac amyloidosis has high associated morbidity and, until recently, limited treatment options. This review discusses the mechanism and clinical trial performance of multiple emerging therapies. Additional studies should identify optimal treatment paradigms and biomarker strategies for cardiac response to therapy.

Reproducibility and repeatability of assessment of myocardial light chain amyloidosis burden using 18F-florbetapir PET/CT

“…(b) A similar study in patients with transthyretin amyloid (ATTR) should be undertaken, as, although this is a different disease, it makes up a significant CA burden 2 and treatment is progressing, particularly if the disease is detected at an early stage. 6 Note that for ATTR, Maurer et al 4 acknowledge that PET with 11C-PIB or 18 F-florbetapir or 18 F-florbetaben is more sensitive compared to SPECT, CMR, and Echocardiography. (c) The relationship between 18 F-florbetapir uptake and clinical markers of cardiac function should be better determined, including biomarkers such as BNP levels.…”

“…As AL and ATTR appear to have somewhat different clinical outcomes and response to therapy, 4,6 there is some importance to being able to differentiate these two entities, if possible, with non-invasive imaging. With SPECT/ 99m Tc Pyrophosphate, Ultrasound, and MRI, differentiation between AL and ATTR is difficult.…”

“…7 Early and accurate detection of amyloid may play an important role if it can be demonstrated that concurrent early introduction of effective therapies will ultimately alter patient outcomes. 6 Hence, the reproducibility and repeatability of 18 F-florbetapir presented by the Brigham and Women's hospital group is very impressive, and given the superior resolution and sensitivity of PET over SPECT for cardiac, even with the new CZT pinhole cameras, 8,9 it is unlikely that SPECT can be competitive to accomplish the goal of early disease detection. The intra-and inter-observer linear regressions that were demonstrated by the authors are outstanding especially when one considers that the readers were inexperienced, the Bland-Altman plot showed no offset and the Carimas software is freely available.…”

Advances in the Treatment of Cardiac Amyloidosis

“…In ATTR amyloidosis, they come from the transthyretin protein produced in the liver. ATTR amyloidosis more frequently comes from wild-type protein due to age-related misfolding (ATTRwt) and less often from misfolding of variant TTR in patients with a mutation in the TTR gene (ATTRh) [4].…”

Prognostic Value of Right Ventricular Dysfunction in Patients With AL Amyloidosis: Comparison of Different Techniques by Cardiac Magnetic Resonance

“…Cardiac involvement is up to 70% of AL amyloidosis patients, 3 and is the most important determinant of outcome 4 . In the past decade, several novel treatments have been tested in AL amyloidosis, but the outcome still remains poor in cases of organ advanced involvement 5 …”