Two-hit strategy for treatment of AL amyloidosis. Schematic representation of the amyloid cascade and targets for intervention. Suppressing the production of the amyloid precursor by anticlone immunochemotherapy extinguishes the cascade and direct organ toxicity and promotes amyloid resorption, thus favoring recovery of organ function and extending survival. Promoting amyloid resorption using passive immunotherapy should help restore tissue architecture and reduce amyloid fibril-mediated toxicity, thus improving organ function and survival. The 2-hit strategy should be synergic, abbreviating the time to organ response and possibly leading to a cure of this disease. Black arrows indicate the flow of molecular events; blue arrows indicate possible effect on target organs; red arrows indicate therapeutic interventions. BMPC, bone marrow plasma cell; mAb, monoclonal antibody.