Patient outcomes in light chain (AL) amyloidosis: The clock is ticking from symptoms to diagnosis

Abstract

Introduction Symptomology of AL amyloidosis can be vague, with a broad range of manifestations and potential etiologies. We sought to determine whether time from initial patient‐reported symptom onset to diagnosis was associated with survival. Methods The Boston University Amyloidosis Patient Database was queried for patients with AL amyloidosis who presented to the Center for initial evaluation from 2010 to 2015. Results A total of 324 patients with AL amyloidosis were evaluated for initial evaluation. The median time to diagnosis from initial symptom onset was 7.1 months (range, 0‐61). At data cutoff, 60.2% (n = 195) of patients were alive; of those, the majority were diagnosed <6 months from initial symptoms (52.3%, n = 102). In contrast, time to diagnosis from symptom onset was >6 months in 63.6% (n = 82) of patients who did not survive at the time of data cutoff (P = .0005). Survival analysis of time from diagnosis to death or data cutoff stratified by time from patient‐reported symptom onset to diagnosis (<6, 6‐12, and >12 months) showed significant differences among groups (P = .001). Additionally, multivariable regression demonstrated that an increase in time from self‐reported symptom onset to diagnosis was significantly associated with an increased risk of death (HR = 1.02, 95% CI = 1.01‐1.04, P = .002). Conclusion These results support the importance of early diagnosis for patients with AL amyloidosis.

Diagnostic delay and characterization of the clinical prodrome in AL amyloidosis among 1523 US adults diagnosed between 2001 and 2019

“…As observed in prior questionnaires, half of patients saw ≥5 providers and >33% were hospitalized more than once prior to diagnosis 14 . Our study supports prior case series and questionnaire findings on the prevalence of cardiac and renal involvement at diagnosis (cardiac: 77% vs 76 22 ; renal: 62% vs 61%‐68% 10,14,22,23 ), as well as findings that the earliest signs/symptoms are generally non‐specific or common neurological symptoms that are unlikely to raise suspicion of AL amyloidosis 14,24 . These results suggest that education targeting neurologists could aid with earlier identification.…”

“…We found that the diagnostic journey is long, with half of patients still undiagnosed with AL amyloidosis 2.7 years after symptom onset. The diagnostic delay in our study is 2 to 3 times longer than the median delay of 7 to 12 months found in prior questionnaires and patient histories that are more subject to recall or response bias 10,14 . For example, previously published questionnaires were implemented an average of 4.5 years after AL amyloidosis diagnosis, requiring patients to remember prior symptoms long after they began 14 .…”

“…Diagnosis delays are a likely cause of early mortality, with single‐institution retrospective chart reviews showing that patients with diagnostic delays have significantly shorter survival than those without a delay 10,11 . The longer diagnosis is delayed, the more advanced the organ damage at diagnosis and the less likely plasma cell treatments can reverse organ failure and lengthen survival.…”

“…Evidence on distinctive patterns of signs/symptoms in the clinical prodrome could inform strategies for detecting AL amyloidosis earlier. Although some evidence on the clinical prodrome and diagnosis delay has been reported from prior questionnaires and single‐center studies, these results are significantly hampered by recall bias of subjects, subjectivity in chart reviews, and referral center bias 10,11,14 . To overcome these limitations, we sought to perform a study that objectively ascertained the prevalence, overlap, and timing of AL amyloidosis signs/symptoms and health care utilization during the clinical prodrome of a broad, commercially insured population with AL amyloidosis in the United States (US).…”

Marked progress in AL amyloidosis survival: a 40-year longitudinal natural history study

“…In an advocacy group-led questionnaire study, over one-third of patients with AL amyloidosis reported that their symptoms preceded diagnosis by more than one year [ 39 ]. Longer diagnostic interval was independently associated with higher risk of death in a recent report from our center [ 40 ]. However, findings from the current study provide grounds for optimism.…”