Early improvements in cardiac and hematologic responses predict better survival outcomes for patients being treated for stage IIIb immunoglobulin light chain (AL) amyloidosis, according to research published in Blood Advances.

Researchers leveraged a prospectively maintained database to identify baseline factors

predictive of early treatment response and prognostic for survival in a large cohort of patients with stage IIIb AL amyloidosis (according to the modified Mayo 2004 and Boston University staging systems).

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They identified 142 patients newly diagnosed with stage IIIb AL amyloidosis between 2007 and 2022 (median age, 66 years; range, 40-90 years; 70% male). Most patients (71%) received upfront treatment with a bortezomib- or daratumumab-containing regimen.

After a median follow-up time of 60 months, patients had a median overall survival (OS) of 9 months. Baseline factors independently associated with shorter OS included >6 months from symptom onset to diagnosis (hazard ratio [HR], 1.94; P =.003), bone marrow plasmacytosis of ≥10% (HR, 1.98; P =.01), troponin I level of >0.635 ng/mL (HR, 1.62; P=.04), New York Heart Association class III/IV (HR, 1.67; P =.04), and walking a distance of <200 meters in the 6-minute walk test (HR 1.85; P =.01).

Patients who achieved early hematologic (within 1 month) and cardiac (within 3 months) responses had significantly longer survival. The median OS was 47 months in  patients with a hematologic very good partial response, 25 months in those with a partial response, and 5 months in those with no response (P <.0001).

The median OS was significantly longer in patients with cardiac response vs those with no response at 3 months (47 vs 11 months; P <.0001).

In multivariable modeling, bortezomib use was associated with early hematologic (odds ratio [OR], 4.54; P =.03) and cardiac (OR, 5.11; P =.04) responses and longer OS (HR, 0.43; P <.001). Factors associated with lower odds of an early cardiac response were >6 months from symptom onset to diagnosis (OR, 0.27; P =.01) and a dFLC (difference between the involved and uninvolved free light chains) level of >350 mg/L (OR, 0.21; P =.03).

“Although treatment can induce early hematologic responses, many patients succumb to cardiac complications before organ improvement can occur,” the study authors wrote in their report. “Our data validate that achieving an early and deep hematologic response is a critical treatment goal for patients with stage IIIb AL amyloidosis.”

Limitations of the study included the retrospective nature, potential referral bias, and the need to use imputation for missing data.


Gustine JN, Staron A, Mendelson L, et al. Predictors of treatment response and survival outcomes in patients with advanced cardiac AL amyloidosis. Blood Adv. Published online August 15, 2023. doi:10.1182/bloodadvances.2023010324