Impact of cytogenetic abnormalities on treatment outcomes in patients with amyloid light-chain amyloidosis: subanalyses from the ANDROMEDA study

Amyloid. 2023 Sep;30(3):268-278. doi: 10.1080/13506129.2022.2164488. Epub 2023 Feb 13.

Abstract

Background: Cytogenetic abnormalities are common in patients with amyloid light-chain (AL) amyloidosis; some are associated with poorer outcomes. This post hoc analysis of ANDROMEDA evaluated the impact of certain cytogenetic abnormalities on outcomes in this patient population.

Methods: Patients with newly diagnosed AL amyloidosis were randomised 1:1 to daratumumab, bortezomib, cyclophosphamide, and dexamethasone (D-VCd) or VCd. Outcomes were evaluated in the intent-to-treat (ITT) population and in patients with t(11;14), amp1q21, del13q14, and del17p13.

Results: Overall, 321 patients had cytogenetic testing (D-VCd, n = 155; VCd, n = 166); most common abnormalities were t(11;14) and amp1q21. At a median follow-up of 20.3 months, haematologic complete response rates were higher with D-VCd vs VCd across all cytogenetic subgroups and organ response rates were numerically higher with D-VCd vs VCd across most subgroups. Point estimates for hazard ratio of major organ deterioration-PFS and -EFS favoured D-VCd over VCd for all cytogenetic subgroups. Deep haematologic responses (involved minus uninvolved free light chains [FLC] <10 mg/L or involved FLC ≤20 mg/L) were seen in more patients with D-VCd than VCd in all ITT and t(11;14) cohorts.

Conclusions: These results support the use of D-VCd as standard of care in patients with newly diagnosed AL amyloidosis regardless of cytogenetic abnormalities.

Keywords: haematologic response; AL amyloidosis; cytogenetic; daratumumab; organ response.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Bortezomib / therapeutic use
  • Chromosome Aberrations
  • Cyclophosphamide / therapeutic use
  • Dexamethasone / therapeutic use
  • Humans
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Light-chain Amyloidosis* / drug therapy
  • Immunoglobulin Light-chain Amyloidosis* / genetics
  • Treatment Outcome

Substances

  • Bortezomib
  • Cyclophosphamide
  • Immunoglobulin Light Chains
  • Dexamethasone