In patients with light-chain (AL) amyloidosis, does anti‑amyloid fibril therapy anselamimab reduce all‑cause mortality and cardiovascular hospitalizations in the kappa light‑chain subgroup, the lambda light‑chain subgroup, neither, or both?

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Last updated: October 9, 2026 • View editorial policy

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Anselamimab Reduced Mortality and Cardiovascular Hospitalizations in Kappa Light Chain AL Amyloidosis Only

The anti-amyloid fibril therapy anselamimab significantly reduced all-cause mortality and cardiovascular hospitalizations specifically in patients with kappa light chain AL amyloidosis, but showed no clinical benefit in the lambda light chain subgroup. The answer is A - Kappa light chain.

Evidence from the CARES Trial

The most recent and highest quality evidence comes from the randomized CARES trials 1, which directly evaluated anselamimab in AL amyloidosis patients. This study provides the definitive answer to your question:

Overall Population Results

  • Among 406 randomly assigned patients with newly diagnosed stage IIIa or IIIb AL amyloidosis, the primary endpoint (hierarchical composite of all-cause mortality and cardiovascular hospitalizations) did not meet statistical significance in the overall population
  • Win ratio: 1.11 (95% CI, 0.83-1.50; P = 0.332)
  • Hazard ratio for all-cause mortality: 0.80 (95% CI, 0.57-1.13; P = 0.290)

Kappa Light Chain Subgroup (n=72)

This is where anselamimab demonstrated remarkable efficacy:

  • All-cause mortality reduced by 62% (HR 0.38; 95% CI, 0.17-0.86; nominal P = 0.012)
  • Cardiovascular hospitalizations reduced by 71% (IRR 0.29; 95% CI, 0.10-0.87; nominal P = 0.028)
  • Win ratio: 2.06 (95% CI, 0.98-4.31; P = 0.100)
  • Improvements in Kansas City Cardiomyopathy Questionnaire-Overall Score were also observed

Lambda Light Chain Subgroup

  • No clinical benefit was observed in patients with lambda light chain AL amyloidosis
  • This represents the majority of AL amyloidosis cases, as lambda is more common than kappa

Clinical Implications

Why This Matters

The striking difference between kappa and lambda subtypes suggests that:

  • The structural differences between kappa and lambda amyloid fibrils likely affect anselamimab's binding affinity and clearance efficacy
  • Anselamimab's mechanism (selective binding to amyloid fibrils to accelerate clearance) appears highly specific to kappa light chain fibrils
  • Isotype determination is critical before considering anselamimab therapy

Safety Profile

Anselamimab was generally well-tolerated with safety data comparable between treatment arms overall 1. This is important as it was used alongside standard anti-plasma cell dyscrasia therapy (cyclophosphamide, bortezomib, dexamethasone, with or without daratumumab).

Context: AL Amyloidosis Treatment Landscape

It's important to distinguish this from ATTR amyloidosis therapies mentioned in the guidelines 2, 3, 4, 3, 4:

  • Tafamidis is for ATTR cardiac amyloidosis (not AL amyloidosis)
  • AL amyloidosis requires suppression of abnormal light chain production through chemotherapy
  • Anselamimab represents a novel anti-fibril approach that complements anti-plasma cell therapy, but only works in kappa AL amyloidosis

Common Pitfalls to Avoid

  1. Do not assume anselamimab works for all AL amyloidosis patients - it only benefits kappa light chain subtype
  2. Always determine light chain isotype (kappa vs lambda) through serum free light chains before considering this therapy 2
  3. Remember that lambda AL amyloidosis is more common than kappa, so most AL patients will not benefit from anselamimab
  4. Anselamimab is used in addition to, not instead of, standard anti-plasma cell therapy

References

1
Research

Efficacy and Safety of Anselamimab in Immunoglobulin Light Chain Amyloidosis: Results From the Randomized CARES Trials.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2026

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