Novel Prognostic and Stratification Index Determined Survival Outcomes for Burkitt Lymphoma

Andrew M. Evens, DO, MSc, FACP

A collaborative effort between Rutgers Cancer Institute of New Jersey and RWJBarnabas Health has led to the discovery and validation of the novel Burkitt Lymphoma International Prognostic Index (BL-IPI), a model for prognostication of patients with Burkitt lymphoma.

“As part of an international collaborative, we developed and validated a simple yet robust prognostic model that accounts for the unique characteristics of Burkitt lymphoma to aid in risk stratification, interpretation of clinical trials, and targeted development of innovative treatment approaches," Andrew M. Evens, DO, MSc, FACP, professor of medicine at Rutgers Robert Wood Johnson Medical School, associate director for clinical services, director of the Lymphoma Program at Rutgers Cancer Institute, medical director of the Oncology Service Line at RWJBarnabas Health, and lead investigator of the study, said in a statement.

According to findings from a real-world validation study published in the Journal of Clinical Oncology, BL-IPI can aid in the prognostication and stratification of patients with Burkitt lymphoma who are enrolled in clinical trials.

The data set analyzed included 633 adult patients who were treated in 30 United States centers between 2009 and 2018. Further validation came from an external data set of patients treated in Europe, Canada, and Australia between 2004 and 2019. The goal of the study was to identify patients with candidate variables that highly correlated with progression-free survival (PFS) and overall survival (OS).

Of the patients who were assessed in the derivation cohort, the median age was 47 years (range, 33-59). At baseline, 22% of the population had an ECOG performance status of ≥ 2, 22% were HIV-positive, 78% had stage III or IV disease, 19% had central nervous system involvement, and 42% had serum lactate dehydrogenase level of > 3× the upper limit of normal. Select patients in the study had central nervous system involvement.

Patients were divided into 3 risk categories: 18% had low-risk disease based on 0 risk factors, 36% had intermediate-risk disease based on 1 risk factor, and the remaining 46% had high-risk disease based on 2 or more risk factors.

The BL-IPI was able to show 3-year OS and PFS rate estimates for each risk group. First, the 3-year PFS rate for patients with low-risk disease was 92%. Among patients with intermediate-risk disease, the 3-year PFS rate was 72%, and the rate was 53% in the high-risk group. The OS rate at 3 years was 96% for patients with low-risk features, 76% in the intermediate-risk group, and 59% in patients with high-risk disease.

Even et al determined from the real-world study that patients with high-risk Burkitt lymphoma had poor outcomes and are unlikely to have improved outcomes using standard therapy. The BL-IPI, therefore, identified a population that would greatly benefit from novel treatment strategies.

"This novel, validated index can help clinicians more accurately identify a prognosis for their adult Burkitt lymphoma patients, as well as advance, targeted clinical research studies," said Adam J. Olszewski, MD, associate professor of medicine, The Warren Alpert Medical School of Brown University, and lead author of the published study, in a statement. "It may engender dual goals of de-escalating treatment intensity for patients with low-risk disease and improving survival rates for the high-risk group, the latter which has suboptimal outcomes with standard therapy and should be considered for novel therapeutic strategies.”

The validation study of the BL-IPI was limited by its retrospective design as well as the fact that no central pathology review was performed. Even et al noted that the prognostic index may not fully predict patient benefit from any therapy. Additionally, the findings of the study may not apply to the elderly Burkitt lymphoma population, because their outcomes are usually impacted by the presence of comorbidities and their ability to tolerate intensive therapy.

"In addition, the availability of BL-IPI may also foster inquiry into molecular differences that lead to divergent clinical outcomes, which are not well explained by the gross indicators of disease burden at diagnosis," Evens stated, in a press release.

_References:

_{Validation of novel prognostic index may better inform Burkitt lymphoma treatment. News release. Rutgers Cancer Institute of New Jersey and RWJBarnabas Health. January 28, 2021. Accessed February 4, 2021.}

_{Olszewski AJ, Jakobsen LH, Collins GP, et al. Burkitt Lymphoma International Prognostic Index. J Clin Oncol. Published online January 27, 2021. doi:10.1200/JCO.20.03288}