Serum-free light chains combined with the Revised International Staging System could further distinguish the superior and inferior clinical outcome of multiple myeloma patients


The Revised International Staging System (R-ISS) was introduced as a powerful prognostic system to stratify patients with newly diagnosed multiple myeloma (NDMM). The serum-free light chain (sFLC) has been developed as a valuable marker to monitor multiple myeloma (MM) progression and response. Therefore, it is imperative to combine R-ISS and sFLC prognostic factors as modified R-ISS (MR-ISS) to better stratify patients into homogeneous survival subgroups, especially to further distinguish the high-risk MM patients who are likely to experience rapid progression or relapse. A total of 595 patients with NDMM were studied retrospectively. We performed the K-adaptive partitioning in 595 NDMM patients to define the MR-ISS classification: stage I includes R-ISS stage I and sFLC ratio < 80 (n = 66); stage III includes R-ISS stage III with sFLC ratio ≥ 80 (n = 87); stage II includes all the remaining conditions (n = 442). The median OS was not reached for MR-ISS stage I, 48.67 months for stage II, and 21.13 months for stage III. A significant OS difference of MR-ISS stage I and III patients has a particularly superior and inferior outcome compared with R-ISS stage I and III, respectively, which showed the similar results in PFS analysis. Validation of results was performed in an independent cohort. Our data indicate that the MR-ISS provides an improved prognostic power compared with R-ISS.

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The authors would like to thank Dr. Brian Durie from Cedars-Sinai Medical Center, Los Angeles, USA, and Dr. Antonio Palumbo from Azienda Ospedaliero-Universitaria Citta` della Salute e della Scienza di Torino, Dipartimento di Oncologia ed Ematologia, Torino, Italy, for the review and editorial assistance.


This work was supported by the International Myeloma Foundation (IMF) Special Research Grant (2013) and in part by the National Natural Science Foundation of China (NFSC 81372543).

Author information




J. Du, W. Fu, and J. Hou were responsible for the study conception and design; J. lu, W. Gao, J. Li, H. He, L. Li, R. Li, L. Zhou, H. Jiang, and W. Chen provided care for study patients; J. Lu, J. Li, and H. He were involved in the collection and assembly of data; J. Du and W. Fu performed the study analysis; all authors participated in data analysis and interpretation, manuscript writing, and provided their final approval of the manuscript.

Corresponding authors

Correspondence to Juan Du or Weijun Fu or Jian Hou.

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The study was conducted in accordance with the principles of the Declaration of Helsinki principles. It was approved by the Ethics Committee at Shanghai Changzheng Hospital.

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The authors declare that they have no competing interest.

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Supplementary Fig. 1

ROC curve demonstrating the sensitivity and specificity of the initial involved/uninvolved sFLC ratio for prognostic value of 595 NDMM patients. The optimal cut-off point for involved/uninvolved sFLC ratio with the highest sensitivity and specificity estimating survival was 80 (AUC = 0.563 (95% CI; 0.468, 0.675), p = 0.007). (PNG 334 kb)

Supplementary Fig. 2

OS and PFS in MR-ISS stages by type of treatment. (A) OS in Pis–based regimens. (B) OS in IMIDs-based regimens. (C) OS in Pis combined with IMIDs–based regimens. (D) PFS in Pis–based regimens. (E) PFS in IMIDs-based regimens. (F) PFS in Pis combined with IMIDs–based regimens. (PNG 4095 kb)

Supplementary Fig. 3

OS and PFS in MR-ISS stages by received transplantation or not. (A) OS in patients received non-transplantation. (B) OS in patients received transplantation. (C) PFS in patients received non-transplantation. (D) PFS in patients received transplantation. (PNG 2995 kb)

Supplementary Fig. 4

OS and PFS in MR-ISS stages by received maintenance therapy or not. (A) OS in patients with maintenance therapy. (B) OS in patients with non-maintenance therapy. (C) PFS in patients with maintenance therapy. (D) PFS in patients with non-maintenance therapy. (PNG 2848 kb)

Supplementary Fig. 5

OS and PFS in MR-ISS stages by renal function. (A) OS in patients with normal renal function. (B) OS in patients with abnormal renal function. (C) PFS in patients with normal renal function. (D) PFS in patients with abnormal renal function. There was no patient in MR-ISS stage III with abnormal renal function so that no plot of stage III showed in curves of Fig. 5B and Fig. 5D. (PNG 2947 kb)

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Du, J., Lu, J., Gao, W. et al. Serum-free light chains combined with the Revised International Staging System could further distinguish the superior and inferior clinical outcome of multiple myeloma patients. Ann Hematol 99, 1779–1791 (2020).

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  • Multiple myeloma
  • Serum-free light chains
  • Revised International Staging System
  • Clinical outcome