Large Study Identifies Predictors of Inferior Survival in Patients With Burkitt Lymphoma

A retrospective analysis of data from 30 U.S. cancer centers found that adults with newly diagnosed Burkitt lymphoma (BL) have modest survival rates and higher treatment-related mortality, compared with survival outcomes reported in clinical trials and case series. Results from the study, reported in Blood, also identified several factors predictive of better survival rates, including treatment with rituximab and treatment at an academic medical center.

“These data represent the largest report to date for adults with newly diagnosed BL,” study author Andrew Evens, DO, of Rutgers Cancer Institute of New Jersey, told ASH Clinical News. In comparison, previously published studies have been small, leading to findings that are challenging to generalize. “Most reports have not had large enough sample size to adequately compare therapeutic regimens in ‘real-world’ cohorts or to robustly examine the potential impact on patient outcomes as well as prognostication,” he added.

The retrospective analysis conducted by Dr. Evens and his colleagues included 641 patients with newly diagnosed BL treated between 2009 and 2018 across 30 cancer centers. The authors reviewed a deidentified database to determine patient demographics, clinicopathologic information, progression-free survival (PFS), overall survival (OS), and treatment-related mortality.

In the overall cohort, the median age was 47 years (range = 18-88), and most patients (76%) were men. Approximately 72% of patients presented with decreased functional status, whereas 28% of patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0.

The treatment-related mortality rate was 10% and most deaths were related to sepsis, followed by gastrointestinal bleed/perforation and respiratory failure. Treatment-related mortality more frequently occurred with the regimen of cyclophosphamide, vincristine, doxorubicin, and a dexamethasone/high-dose methotrexate and cytarabine (hyperCVAD/MA). “This may be partly explained by a less biased case selection enriched with patients presenting with higher-risk features such as poor performance status, organ dysfunction, and/or central nervous system (CNS) disease,” said Dr. Evens, “which may represent exclusion criteria for clinical trials.”

The 3-year PFS rate was 64%, and the 3-year OS rate was 70%. Patients who were treated with rituximab had improved OS and PFS rates, compared with patients who did not receive rituximab:

  • OS: 72% vs. 44% (p<0.001)
  • PFS: 67% vs. 38% (p<0.001)

Patients treated at academic centers also had better survival compared with patients treated at community centers, both in terms of PFS (67% vs. 46%, p=0.006) and OS (72% vs. 53%; p=0.01).

However, older age, poorer ECOG performance status, higher lactate dehydrogenase levels, and CNS involvement were associated with inferior survival (TABLE).

Dr. Evens noted that the absence of any of these four prognostic factors described a group of patients with newly diagnosed BL who had PFS exceeding 90%. “Although our index showed good performance upon internal validation,” he said, “further external validation is warranted in a different geographic and/or temporal setting to fully assess its calibration and clinical usefulness.”

The primary limitation of this study is its retrospective nature. “Staging evaluations and therapy were completed at the discretion of treating physicians, the latter which likely induced bias,” said Dr. Evens. In spite of these limitations, he added, the large sample size produced “sufficient power to establish optimal cutoffs for key baseline factors, such as age and lactate dehydrogenase, that were able to be integrated in the prognostic survival model.”

“Despite astoundingly optimistic results of some clinical trials, the reality of BL is starker, with only 64% of patients achieving long-term survival without relapse, and 10% dying early from toxicities of current regimens which rely on intensive cytotoxic chemotherapy,” corresponding author Adam Olszewski, MD, of Rhode Island Hospital, told ASH Clinical News. Dr. Olszewski hopes the findings from this study may inspire additional research on improved therapies that are more effective and less toxic – an ongoing need for BL.

 The authors report no relevant conflicts of interest.

Reference

Evens AM, Danilov AV, Jagadeesh D, et al. Burkitt lymphoma in the modern era: real world outcomes and prognostication across 30 US cancer centers. Blood. 2020 July 14. [Epub ahead of print]