Presentation and outcome with second-line treatment in AL amyloidosis previously sensitive to nontransplant therapies

The management of light chain (AL) amyloidosis has improved in recent years thanks to accurate biomarker-based staging systems and response criteria and availability of novel effective therapies. However, previous studies have focused on newly diagnosed patients, and little is known on relapsed patients, despite the fact that trials of new agents are often performed in this setting. In the present study, we report the outcome of 259 patients who responded to up-front therapy. Ninety-two patients (35%) needed second-line therapy after a median of 49 months. Cardiac and renal progression were observed in 22% and 12% of patients who received second-line therapy, respectively. Complete response after up-front treatment and frontline therapy with combined bortezomib, melphalan, and dexamethasone independently prolonged time to second-line therapy. Median survival of relapsing patients was 59 months. Patients who had a "high-risk dFLC progression," which we defined as a difference between involved and uninvolved free light chains (dFLC) of >20 mg/L, a level >20% of baseline value, and a >50% increase from the value reached at best response, had a shorter survival after initiation of second-line therapy on univariate, but not on multivariate, analysis, where cardiac progression was the only independent predictor of survival after starting rescue treatment. Patients with AL amyloidosis who need second-line therapy after response to up-front treatment generally have a good outcome. A "high-risk dFLC progression" should trigger rescue treatment, and cardiac progression should not be awaited.