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

Shaji Kumar, Angela Dispenzieri, Divaya Bhutani, Morie Gertz, Ashutosh Wechalekar, Giovanni Palladini, Raymond Comenzo, Rafael Fonseca, Arnaud Jaccard, Efstathios Kastritis, Stefan Schönland, Charles la Porte, Huiling Pei, Nam Phuong Tran, Giampaolo Merlini

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)268-278
Number of pages11
JournalAmyloid
Volume30
Issue number3
DOIs
StatePublished - 2023

Keywords

  • AL amyloidosis
  • cytogenetic
  • daratumumab
  • haematologic response
  • organ response

ASJC Scopus subject areas

  • Internal Medicine

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