External validation and comparison of IPI, R-IPI, and NCCN-IPI in diffuse large B-cell lymphoma patients treated with R-CHOP to predict 2-year progression-free survival

Hematology. 2022 Dec;27(1):1237-1245. doi: 10.1080/16078454.2022.2147916.

Abstract

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive lymphoma. The standard first-line therapy for DLBCL consists of rituximab cyclophosphamide doxorubicin vincristine and prednisone (R-CHOP). About 50-70% of patients may be cured by R-CHOP. There was no data on external validation and comparison of the international prognostic index, revised-IPI (R-IPI), and enhanced-IPI (NCCN-IPI) to predict treatment outcomes in the middle-income country with a resourced-limited setting.

Objectives: We aimed to externally validate and compare IPI, R-IPI, and NCCN-IPI in predicting 2-year progression-free survival (2-y PFS) of newly diagnosed DLBCL patients treated with R-CHOP.

Methods: This ambispective observational study recruited consecutive patients diagnosed between 1 January 2014 and 30 June 2020, with the last follow-up on 1 July 2022 from Thammasat University Hospital and Ramathibodi Hospital. We assessed discrimination by Harrell's concordance index (c-index), calibration by calibration plot, and absolute difference in survival (ADS) between the lowest-and the highest-risk groups.

Results: The cohort of 292 patients (median age 63 years and median follow-up 3.6 years) had 131 progressions and 96 deaths. The 2-y PFS was 63%. The c-indices were NCCN-IPI 0.6216, R-IPI 0.6004 (P = 0.215), and IPI 0.6104 (P = 0.463). The calibration plots of NCCN-IPI and R-IPI showed nearly perfect agreement (moderate strength), while IPI had miscalibrations. The ADSs were NCCN-IPI 52%, R-IPI 42%, and IPI 25%.

Conclusion: NCCN-IPI is the best prognostic index compared to IPI and R-IPI in prior studies. However, the prognostic model for DLBCL patients treated with R-CHOP requires updating or integrating biomarkers to improve discrimination to the acceptable level (c-index 0.7).

Keywords: Diffuse large B-cell lymphoma; R-CHOP; comparison; enhanced-international prognostic index; external validation; international prognostic index; progression-free survival; revised-international prognostic index.

Publication types

  • Observational Study

MeSH terms

  • Cyclophosphamide / therapeutic use
  • Doxorubicin / therapeutic use
  • Humans
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Middle Aged
  • Prednisone / therapeutic use
  • Progression-Free Survival
  • Rituximab / therapeutic use
  • Vincristine / therapeutic use

Substances

  • Vincristine
  • Rituximab
  • Prednisone
  • Cyclophosphamide
  • Doxorubicin