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

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:

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

Disclosure statement

S. Kumar served in consultancy roles for AbbVie, Adaptive Biotechnologies, Amgen, Bristol-Myers Squibb, Celgene/Bristol-Myers Squibb, Genecentrix, Genentech/Roche, Janssen Oncology, Karyopharm, Kite Pharma, Merck, Oncopeptides, and Takeda, on advisory boards for AbbVie, Amgen, Celgene/Bristol-Myers Squibb, Genentech/Roche, Janssen Oncology, and Takeda, and on an independent review committee for Oncopeptides; and received honoraria from Dr. Reddy’s Laboratories, funding from Amgen, Bristol-Myers Squibb, Cargen, Kite Pharma, MedImmune, Merck, Novartis, Sanofi, and Tenebio, and clinical trial funding from AbbVie, Celgene/Bristol-Myers Squibb, Genentech/Roche, Janssen Oncology, and Takeda.

A. Dispenzieri has received research funding from Alnylam, Celgene, Intellia, Janssen, Pfizer, and Takeda.

D. Bhutani has received clinical trial funding from Sanofi pharmaceuticals and served as a consultant for Sanofi Genzyme.

M. Gertz has received honoraria from Spectrum, Janssen, Celgene, Alnylam, and Ionis, and research funding from Spectrum.

A. Wechalekar has received honoraria from Celgene, Janssen, and Takeda, served on advisory boards for Caelum and Janssen, and received travel funding from Takeda.

G. Palladini has served on the advisory boards of Alexion, Argobio, Janssen, and Protego, received honoraria from Alexion, Argobio, Janssen, Pfizer, Protego, Prothena, Sebia, Siemens, and The Binding Site, and received research funding from Gate Bioscience and The Binding Site.

R. Comenzo has served on advisory boards for Amgen, Caleum, Janssen, Karyopharm, Prothena, Sanofi, Takeda, and Unum, and received research funding from Amgen, Janssen, Karyopharm, and Takeda.

R. Fonseca served as a consultant for AbbVie, Aduro, Amgen, Bayer, BMS/Celgene, GlaxoSmithKline, Janssen, Juno, Kite, Merck, Novartis, Oncotracker, Pharmacyclics, and Sanofi; and participated in an advisory board for Adaptive Biotechnologies.

A. Jaccard has served in consulting or advisory roles for Janssen and received honoraria and research and travel funding from Janssen.

E. Kastritis has served in a consulting role for Amgen, Genesis Pharma, Janssen, Pfizer, GSK, Prothena and Takeda, received honoraria from Amgen, Genesis Pharma, Janssen, Pfizer, GSK and Takeda, and received research funding from Amgen and Janssen.

S. Schönland received honoraria and travel support or research funding by Janssen, Prothena, and Takeda.

C. la Porte was employed by Janssen at the time of this research.

H. Pei and N.P. Tran are employed by Janssen and hold company stock.

G. Merlini has nothing to disclose.

Data availability statement

The data sharing policy of Janssen Pharmaceutical Companies of Johnson & Johnson is available at https://www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at http://yoda.yale.edu.

Additional information

Funding

This study was sponsored by Janssen Research & Development, LLC. Medical writing and editorial support were provided by Justine Lempart, PhD, and Karen Pemberton, PhD, of Eloquent Scientific Solutions and funded by Janssen Global Services, LLC.