Who Is Treating AL Amyloidosis and How Are They Doing It? Results of a Global Physician Survey

Background: In light chain (AL) amyloidosis, aggregates of misfolded light chain or fragments of a light chain produced by clonal plasma cells accumulate in various organs and tissues, leading to progressive organ failure. This aggregation is particularly catastrophic when the heart is affected and is the primary cause of death. Diagnosis is often delayed because symptoms at onset can mimic those of other common conditions. Current treatments are aimed at eliminating the clonal plasma cells that produce the toxic light chains; however, optimal treatment regimens are undefined, and no therapies have received regulatory approval. Physicians were surveyed to identify potential investigators for clinical trials of AL amyloidosis and to detect regional treatment patterns. Here we present characteristics of physicians who typically treat this rare disease, the treatments they use, and differences across countries and regions.

Method: The survey was designed and conducted by Prothena Biosciences in association with a contract research organization. Physicians (n = 133) in 22 countries were supplied the survey by email, and data were evaluated using descriptive statistics and χ² tests.

Results: Respondents (N = 116) represented 21 countries and 5 continents. The primary therapeutic area was hematology (80.2%), followed by oncology (14.7%), with the remaining physicians specializing in cardiology (2.6%) and internal medicine (2.6%). Most physicians (90.5%) practiced in an academic or university setting. The majority (99; 85.3%) self-identified as practitioners at major referral centers. These physicians saw an average of 65 patients with confirmed diagnoses of AL amyloidosis each year; 23 reported seeing ≥50 such patients each year, and 6 reported seeing ≥100 such patients each year. With the exception of one institution, physicians at nonreferral centers saw ≤18 patients with confirmed AL amyloidosis each year. Patients with newly diagnosed AL amyloidosis and those who were treatment naive accounted for 53.9% of all patients seen; of these, 60.4% had cardiac involvement. Most institutions (75.4%) preferred to use proteasome-inhibiting (PI) agents (bortezomib or combination) or marrow ablation followed by autologous stem cell transplantation (ASCT) in select patients (21.1%); these values generally paralleled actual treatments provided (64.0% and 20.6%, respectively). The remaining patients received treatments that did not include PI agents or ASCT. Equal percentages of European and North American responding physicians (65.4% vs 63.7%) reported using PI agents as initial treatment. However, significantly fewer European physicians than North American physicians used marrow ablation followed by ASCT (16.7% vs 26.4%; P < 0.05). Respondents from Asia, Australia, and South America, though fewer, primarily used PI agents as initial therapy and least frequently used marrow ablation and ASCT. Among all respondents, ASCT was performed primarily after chemotherapy (30%) rather than as initial treatment (13%); however, average timing to proceed to ASCT varied broadly (weeks to months).

Conclusions: AL amyloidosis is treated primarily by hematologists with the use of proteasome-inhibiting agents, either alone or in combination. There is marked regional variation in the use of marrow ablation with ASCT. AL amyloidosis is a rare disease that, despite these treatments, remains progressive and fatal. Optimal treatment regimens remain undefined, and no specific therapeutic approaches exist that reverse organ dysfunction.