Predictors of Early Death in Patients With Wild-Type Transthyretin Cardiac Amyloidosis.

Background: For the time being, tafamidis is the only approved treatment for wild-type transthyretin cardiac amyloidosis. However, benefits on all-cause death only emerge after ≈18 months. The current available staging systems are unable to specifically discriminate patients at high risk of death within 18 months from diagnosis, and the selection of patients who are expected to benefit from tafamidis is left to the clinical judgment of treating physicians, being often based primarily (and sometimes only) on age.

Development and Validation of Staging Systems for AA Amyloidosis.

Key Points: Patients with AA amyloidosis and age ≥65 years, eGFR <45 ml/min per 1.73 m, and -terminal type-B natriuretic peptide >1000 ng/L and/or type-B natriuretic peptide >130 ng/L at diagnosis have poorer survival. Proteinuria >3.

Sequential response-driven bortezomib-based therapy followed by autologous stem cell transplant in AL amyloidosis.

Autologous stem cell transplant (ASCT) is highly effective in selected patients with light chain (AL) amyloidosis. Bortezomib, preceding or following ASCT, improves responses. Satisfactory responses, including at least a partial response, very good partial response (VGPR) with organ response, or complete response, can be observed after induction therapy alone.

Indicators of profound hematologic response in AL amyloidosis: complete response remains the goal of therapy.

In AL amyloidosis complete response (aCR) is defined as negative serum and urine immunofixation with normalized free light chain ratio (FLCR). However, achievement of low levels of involved FLC (iFLC) or difference between iFLC and uninvolved FLC (dFLC) are also relevant endpoints for treatment. We divided 434 consecutive patients with AL amyloidosis into five groups according to response 6 months after treatment initiation: aCR, iFLC <20 mg/L, normalized-iFLC, dFLC <10 mg/L, and normalized FLC ratio.

High rate of profound clonal and renal responses with daratumumab treatment in heavily pre-treated patients with light chain (AL) amyloidosis and high bone marrow plasma cell infiltrate.

Daratumumab demonstrated activity in the treatment of AL amyloidosis in two recently concluded phase II clinical trials in relapsed and refractory patients. Its role in upfront therapy is under evaluation in a phase III study. In this report we evaluated the safety and efficacy of 28-day cycles of daratumumab (single agent or combined with bortezomib or lenalidomide) in 72 previously treated patients with multiple myeloma and AL amyloidosis.