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Record W7108475644 · doi:10.1182/blood-2025-3963

MGUS like phenotype in patients with AL amyloidosis: Impact on clinical outcomes for patients treated with bortezomib-containing regimens (BCR).

2025· article· en· W7108475644 on OpenAlexaboutno aff

Bibliographic record

VenueBlood · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicAmyloidosis: Diagnosis, Treatment, Outcomes
Canadian institutionsnot available
Fundersnot available
KeywordsAL amyloidosisMonoclonal gammopathy of undetermined significanceMultiple myelomaAmyloidosisLog-rank testRetrospective cohort studyStage (stratigraphy)Survival analysisMelphalan

Abstract

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Abstract Multiple Myeloma and Light-chain (AL) amyloidosis are clonal plasma cell disorders with different clinical expressions. Recently, Burgos L et al. described an algorithm to classify patients with Monoclonal Gammopathy of Clinical Significance (MGUS)-like phenotype that was developed based on two flow cytometry parameters as well as revised ISS stage, transplant eligibility and depth of response. In our analysis, we used the European modification of the Mayo staging system for AL amyloidosis that refines the original Mayo staging by incorporating NT-proBNP levels for further risk stratification within stage III patients and as such this system was used instead of the revised stage for our analysis. The calculator is available online (). Methods We performed a retrospective study in patients with new diagnosis of AL amyloidosis treated with Bortezomib-Containing Regimens (BCR) at the Amyloidosis Program of Calgary (APC).An algorithm to identify patients having MGUS-like phenotype was used as reported recently. In the current study, 114 patients treated with BCR from 01/2012 to 04/2025 were evaluated. The primary objective of the study was to assess the impact of MGUS-like phenotype on survival outcomes for patients treated with BCR at the APC.A p value of <0.05 was considered significant. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test. Progression-Free Survival (PFS) was defined as the time from treatment to disease progression or death, while overall survival (OS) was defined from the date of treatment to the date of death from any cause. All statistical analyses were performed by using the SPSS 24.0 software. Results A total of 114 patients were evaluated. Median age was 66 years (range 39-88) and 59.6% were male. All patients included in this study received first-line BCR, 50 patients were treated with CyBorD (Cyclophosphamide, Bortezomib and Dexamethasone), 27 with Daratumumab-CyBorD and 36 with CyBorMe (Cyclophosphamide, Bortezomib and Methylprednisolone) with a median of 4 cycles (1-54). In total, 83 (72.8%) and 84 patients (73.7%) had cardiac and renal involvement, respectively. Based on the results obtained from the MGUS-like classifier, 42 patients (36.8%) were described as having MGUS-like phenotype compared to 26 (22.8%) with intermediate phenotype and 46 (40.4%) with MM-like phenotype. VGPR or better was observed in 35/42 (83.3%) compared to 17/26 (65.3%) for the intermediate-like and 22/46 (47%) for the MM-like group, respectively (p=0.002). At the time of analysis, 62 patients (54.4%) are alive and 72 have progressed or died (63.2%). In addition, patients with AL amyloidosis and a MGUS-like phenotype had a better overall survival compared to patients with intermediate or MM-like phenotype (Estimated of 149 months vs Estimated 80.4 and 28.7 months, respectively, p=0.001). Further, Progression-Free survival was longer in the MGUS like phenotype group of patients compared to the intermediate and MM-like groups (72.4 versus 58.2 and 20.9 months, respectively, p=0.003). In a multivariate analysis, MGUS like phenotype, depth of response and less advanced staging correlated with better survival. Summary & Conclusion We report here the role of MGUS-like phenotype for patients with AL amyloidosis treated with BCR at the Amyloidosis Program of Calgary. Our data validates the effect of MGUS like phenotype on survival in a consecutive treated group of AL amyloidosis cases.

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How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.009
GPT teacher head0.294
Teacher spread0.284 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

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Citations0
Published2025
Admission routes1
Has abstractyes

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