Researchers have created a prognostic index specific to Burkitt lymphoma (BL) that will allow for simplified stratification and comparison of risk distribution in geographically diverse cohorts. Adam J. Olszewski, MD, of Lifespan Cancer Institute at Rhode Island Hospital and the Warren Alpert Medical School of Brown University, presented information on the new prognostic index (BL-IPI) at the 2020 ASH Annual Meeting.
“Unfortunately, the traditional International Prognostic Index [IPI] is not very useful in this disease primarily because BL is quite different from diffuse large B-cell lymphoma,” Dr. Olszewski said. “It presents at a younger age, the vast majority of patients present with advanced disease and abnormal lactate dehydrogenase [LDH] levels, which means these factors are not useful in identifying patients that are truly high risk.”
The prognostic index was derived using a large real-world evidence cohort of 633 U.S. adults treated for BL from 2009 to 2018. The primary outcome was progression-free survival (PFS), defined as the time from diagnosis until recurrence, progression, death, or censoring. The researchers identified optimal prognostic cutoffs of age 40 or older, LDH >3 times the upper limit of normal (ULN), hemoglobin <11.5 g/dL, and albumin <3.5 g/dL.
The multivariable model established four independent factors prognostic of disease severity: age 40 and older, LDH >3 times ULN, ECOG performance status of 2 or more, and central nervous system (CNS) involvement. Of note, adding stage did not enhance the model. The model categorized the 633 patients in the derivation cohort as:
- low-risk (0 factors; 18%)
- intermediate-risk (1 factor; 36%)
- high-risk (2-4 factors; 46%)
The rates of three-year PFS were 92% for low-risk, 72% for intermediate-risk, and 53% for high-risk patients (p<0.001). For overall survival (OS), rates were 96%, 76%, and 59%, respectively, for the three risk groups (p<0.001).
The researchers also found that the index discriminated outcomes in patients with or without HIV, in those with MYC rearrangements, or those who had been treated with rituximab. BL-IPI also discriminated survival regardless of first-line chemotherapy.
The performance of the prognostic index was validated in an external retrospective dataset of 457 patients treated in centers in the United Kingdom, Scandinavia, Canada, and Australia. In the validation cohort, fewer patients had CNS involvement, while more patients had a performance status or 2 or more and had received treatment with cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC).
The BL-IPI categories were of similar size in the international validation cohort: 15% of patients were low-risk, 35% were intermediate-risk, and 50% were high-risk. The investigators also reported that the index provided similar risk discrimination. PFS and OS estimates at three years were higher in the international cohort compared with the U.S. cohort. Three-year PFS was 96% for low-risk, 82% for intermediate-risk, and 63% for high-risk patients (p<0.001), while OS was 99%, 85%, and 64%, respectively (p<0.001). However, the prognostic index remained predictive in subsets of patients that received rituximab (p<0.001) and in those with advanced stage disease (p<0.001).
Based on these results, Dr. Olszewski said that low-risk patients could be targeted for treatment de-escalation in future studies, while high-risk groups with a low cure rate on current therapies would need new approaches.
The authors report no relevant conflicts of interest.
Olszewski AJ, Jakobsen LH, Collins GP, et al. The Burkitt Lymphoma International Prognostic Index (BL-IPI). Abstract #705. Presented at the 2020 American Society of Hematology Annual Meeting, December 7, 2020.