Burkitt Lymphoma International Prognostic Index

Abstract

Purpose: Burkitt lymphoma (BL) has unique biology and clinical course but lacks a standardized prognostic model. We developed and validated a novel prognostic index specific for BL to aid risk stratification, interpretation of clinical trials, and targeted development of novel treatment approaches.

Methods: We derived the BL International Prognostic Index (BL-IPI) from a real-world data set of adult patients with BL treated with immunochemotherapy in the United States between 2009 and 2018, identifying candidate variables that showed the strongest prognostic association with progression-free survival (PFS). The index was validated in an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019.

Results: In the derivation cohort of 633 patients with BL, age ≥ 40 years, performance status ≥ 2, serum lactate dehydrogenase > 3× upper limit of normal, and CNS involvement were selected as equally weighted factors with an independent prognostic value. The resulting BL-IPI identified groups with low (zero risk factors, 18% of patients), intermediate (one factor, 36% of patients), and high risk (≥ 2 factors, 46% of patients) with 3-year PFS estimates of 92%, 72%, and 53%, respectively, and 3-year overall survival estimates of 96%, 76%, and 59%, respectively. The index discriminated outcomes regardless of HIV status, stage, or first-line chemotherapy regimen. Patient characteristics, relative size of the BL-IPI groupings, and outcome discrimination were consistent in the validation cohort of 457 patients, with 3-year PFS estimates of 96%, 82%, and 63% for low-, intermediate-, and high-risk BL-IPI, respectively.

Conclusion: The BL-IPI provides robust discrimination of survival in adult BL, suitable for use as prognostication and stratification in trials. The high-risk group has suboptimal outcomes with standard therapy and should be considered for innovative treatment approaches.

FIG 1.

Characteristics of the BL-IPI in the derivation (US) cohort: (A) proportion of patients according to the number of risk factors; (B) PFS according to the number of risk factors; PFS of patients with two versus three, and three versus four risk factors was not statistically significantly different, and hence, these groups were combined in the high-risk category; (C) PFS according to BL-IPI risk group; (D) OS according to BL-IPI risk group; 3-year PFS and OS estimates are listed with 95% CIs (in parentheses); P values are from log-rank tests comparing groups sequentially and from an overall log-rank test. BL-IPI, Burkitt lymphoma International Prognostic Index; LDH, lactate dehydrogenase; OS, overall survival; PFS, progression-free survival; ULN, upper limit of normal.

FIG 2.

Performance of the BL-IPI in the validation (international) cohort: (A) PFS according to BL-IPI risk group, (B) OS according to BL-IPI risk group; 3-year PFS and OS estimates are listed with 95% CIs (in parentheses); P values are from log-rank tests comparing groups sequentially and from an overall log-rank test. BL-IPI, Burkitt lymphoma International Prognostic Index; OS, overall survival; PFS, progression-free survival.