Proposing a New Organ Response Criterion for Light Chain Amyloidosis Based on Graded Response

Establishment of validated response criteria that can be measured relatively early and consistently predict overall survival has been a major step forward. The remarkably high rate of overall and deep hematologic response with novel agents indicates that future studies will be based on new, robust, and validated measures of “very deep” response.1

Currently, more patients realize hematologic response, leading to an improved rate and depth of organ response, as therapeutic options for light chain amyloidosis (AL) expand and improve. It was proposed, based on a previous study, that survival discrimination can be based on graded organ response depth criteria.

In this international collaborative study, Eli Muchtar, MD, and colleagues at the Mayo Clinic, sought to validate organ response depth criteria.

The retrospective analysis looked at patients diagnosed between January 2010 and December 2015; patients who attained at least a partial hematologic response for any line of therapy initiated within 12 months from diagnosis were included. Those patients who were not hematologic responders were assumed not to have achieved organ response.2

All patients had an assessable organ to measure response (kidneys: >0.5 g proteinuria/24 hours; heart: N-terminal-pro B-type natriuretic peptide [NT-proBNP] >650 pg/mL or BNP >150 pg/mL; liver: alkaline phosphatase >1.5 upper limit of normal).

Complete response (CR) was defined in terms of various organ end points: for heart, NT-proBNP ≤350 ng/L, BNP ≤80 ng/L; for kidneys, proteinuria ≤200 mg/24 hours in the absence of a decrease in estimated glomerular filtration rate ≥25%; and for liver, serum alkaline phosphatase ≤2× institutional lower limit of normal. Very good partial response (VGPR) was defined as >60% reduction in organ parameter not meeting organ CR. Partial response (PR) was defined as 31% to 60% reduction in organ parameter. No response (NR) was defined as ≤30% reduction in organ parameters.

Six medical centers provided data to be analyzed, and in the overall analysis 579 patients were included in the study. Fifty-eight percent of the patients were male (336/579), and median age at diagnosis was 63 years. At the end of follow-up (median follow-up of surviving patients of 72 months), 65% of patients were alive.

Eighty percent of patients received 1 line of therapy within the initial 12 months from diagnosis. Researchers reported the following best hematologic response breakdown: CR (achieved by 37% of patients), VGPR (40%), and PR (23%). Three hundred fifty-four patients were evaluable for cardiac response, with a median baseline NT-proBNP of 3402 pg/mL.

Depth of cardiac response (5-year overall survival [OS]: 86%, 78%, 62%, and 25% for cardiac CR, VGPR, PR, and NR, respectively; P <.001) was significantly associated with OS. For renal response, 371 patients were evaluable, with a median baseline proteinuria of 5.2 g/24 hours. The depth of renal response was correlated with survival (5-year OS: 91%, 82%, 72%, and 46% for renal CR, VGPR, PR, and NR, respectively; P <.001). In 75 patients, hepatic response was assessable, in whom survival increased with a deeper hepatic response (5-year OS: 100%, 88%, 46%, and 43% for hepatic CR, VGPR, PR, and NR, respectively; P <.001).

The authors concluded that depth of organ response among heart, kidney, and liver involvement correlates with survival. This suggests that similar to the hematologic response criteria, changing organ response criteria to a graded response system from the current system of “response/nonresponse” may be important for clinical trials, particularly because the graded organ response is prognostic when tested for heart, kidney, and liver response.


  1. Palladini G. Hematologic and organ response criteria. Presented at: 2020 International Symposium on Amyloidosis; September 14-18, 2020. Abstract OP23.
  2. Muchtar E, Milani P, Hegenbart U, et al. New organ response criteria for light chain amyloidosis: an international validation study. Presented at: 2020 International Symposium on Amyloidosis; September 14-18, 2020. Abstract OP21.

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