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Deep Sequencing Accurately Predicts Prolonged Survival in Multiple Myeloma Patients

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Key Points

  • A comparison of traditional response criteria and minimal residual disease measurement by deep-sequencing analysis and multiparameter flow cytometry in patients with multiple myeloma found that minimal residual disease negativity by sequencing may be a better prognostic indicator than complete response by traditional response criteria.
  • Patients who were minimal residual disease–negative by sequencing analysis had significantly improved overall and progression-free survival than those who were minimal residual disease–positive.
  • When the analysis was limited to patients in conventional complete response, there was a significantly improved overall survival in the minimal residual disease–negative group.

A study by the Spanish Myeloma Group comparing the prognostic value of traditional response criteria and minimal residual disease measurement in patients with multiple myeloma found that a sequencing-based method called LymphoSIGHT and multiparameter flow cytometry analysis both accurately identified patients negative for minimal residual disease. The findings were presented at the 2013 ASCO Annual Meeting (Abstract 8511).

Study Details

The study compared a deep sequencing–based method called LymphoSIGHT and multiparameter flow cytometry analysis to measure minimal residual disease in patients with multiple myeloma. Investigators found that these methods better predicted prolonged survival than complete response as measured by traditional response criteria. Most patients with multiple myeloma will relapse due to persistent minimal residual disease, said the study authors.

In this study of 68 uniformly treated patients with multiple myeloma enrolled in the Spanish Myeloma Group trials GEM00 and GEM05, the researchers used bone marrow samples obtained from the patients at diagnosis to identify the myeloma clonotype and measure minimal residual disease following treatment.

Using LymphoSIGHT, the researchers identified clonal rearrangements of immunoglobulin genes IGH-VDJ, IGH-DJ, and IGK in diagnostic samples. The deep sequencing assay detected a myeloma-specific gene rearrangement in 59 of the 68 samples (87%). Fifty-six of the 59 patients were tested for minimal residual disease.

Improved Survival in Minimal Residual Disease–negative Group

Of the 56 patients, 45 were positive by deep sequencing at minimal residual disease levels of 10-5 or higher and 11 were minimal residual disease–negative. The investigators found significantly improved overall survival in the minimal residual disease–negative group vs the minimal residual disease–positive group and similar differences in progression-free survival.

When limiting the analysis to the 35 patients in conventional complete response, 24 of the 35 patients were positive by sequencing at minimal residual disease levels of 10-5 and higher, and 10 were minimal residual disease–negative. There was significantly improved overall survival in the minimal residual disease–negative group vs the minimal residual disease–positive group (median not reached vs 80.92 months, P = .041).

The study findings show a strong correlation between multiparameter flow cytometry and deep sequencing minimal residual disease levels in patients with multiple myeloma. For patients in complete response as measured by traditional response criteria, the presence or absence of minimal residual disease by sequencing delineated two groups of patients with significantly different overall survival.

Deep-sequencing analysis of patients who were negative for minimal residual disease, concluded the study researchers, may be a better prognostic indicator than complete response as measured by traditional response criteria.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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