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Nucleic acid based risk assessment and staging for clinical practice in multiple myeloma

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Abstract

The recently introduced Revised International Staging System (R-ISS) for multiple myeloma (MM) integrates albumin, β2 microglobulin, lactate dehydrogenase (LDH) with high-risk cytogenetic aberrations (CA), i.e., t(4;14) and t(14;16) and del17p using fluorescent in situ hybridization (FISH). We evaluated utility of nucleic acid-based tests of multiplex ligation-based probe amplification (MLPA) and quantitative real-time polymerase chain reaction (qRT-PCR) to define the CA and the R-ISS categories as per this approach were evaluated for their ability to predict outcome in terms of response, progression-free (PFS), and overall survival (OS). In this study (n = 180), 17 (9.4%), 118 (65.6%), and 45 (25%) patients were assigned to R-ISS1, R-ISS2, and R-ISS3 categories with statistically significant differences in median PFS (p = 0.02) and OS (p < 0.001).On univariate analysis, serum creatinine, LDH, 17p deletion, chromosome 1q gain, and response after first induction therapy were associated with statistically significant differences (p < 0.05) in PFS and in addition, age> 65 years and use of triplet therapy with OS. On multivariate analysis, only serum creatinine, LDH, and response after first induction therapy retained significance for predicting PFS and in addition, use of triplet therapy retained significance for the OS. The proposed nucleic acid-based algorithm using qRT-PCR and MLPA for R-ISS is resource-effective in terms of small quantities of sample required; feasibility of batch processing and reduced overall cost for the total number of regions evaluated and retained the prognostic significance of R-ISS, making it suitable for clinical practice for molecular characterization of MM.

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Funding

The financial support was provided by Department of Biotechnology (BT/ PR7136 /MED /30/901/2012 and BT/MED/30/SP11006/2015), Ministry of Science & Technology, Government of India, and All India Institute of Medical Sciences, New Delhi (A411/RS) to RG for carrying out the research work.

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Authors and Affiliations

  1. Laboratory Oncology Unit, Dr. B.R.A.IRCH, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, 110029, India

    Ritu Gupta, Gurvinder Kaur, Lata Rani, Nitin Mathur, Meetu Dahiya, Varun Shekhar, Sadaf Khan & Om Dutt Sharma

  2. Department of Medical Oncology, Dr. B.R.A.IRCH, All India Institute of Medical Sciences (AIIMS), Ansari Nagar, New Delhi, 110029, India

    Lalit Kumar, Atul Sharma & Anjali Mookerjee

Authors
  1. Ritu Gupta
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  2. Gurvinder Kaur
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  3. Lalit Kumar
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  4. Lata Rani
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  5. Nitin Mathur
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  6. Atul Sharma
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  7. Meetu Dahiya
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  8. Varun Shekhar
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  9. Sadaf Khan
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  10. Anjali Mookerjee
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  11. Om Dutt Sharma
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Contributions

RG designed the study, analyzed clinical and experimental data, and wrote the manuscript; GK analyzed clinical and experimental data and reviewed the manuscript; LR and NM performed the experiments under the guidance of RG; MD, VS, and SK assisted LR and NM in experimentation part; LK and AS evaluated the clinical data and reviewed the manuscript.

Corresponding author

Correspondence to Ritu Gupta.

Ethics declarations

This study was carried out according to the Helsinki declaration. The informed consent was obtained from all the participants included in this study as per the guidelines of Ethics Committee of All India Institute of Medical Sciences.

Conflict of interest

The authors declare that they have no conflict of interest.

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Gupta, R., Kaur, G., Kumar, L. et al. Nucleic acid based risk assessment and staging for clinical practice in multiple myeloma. Ann Hematol 97, 2447–2454 (2018). https://doi.org/10.1007/s00277-018-3457-8

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  • DOI: https://doi.org/10.1007/s00277-018-3457-8

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