Editor's Note: The "2024 Nanjing Lymphoma Forum" was held in Nanjing from May 11-12, 2024. The conference, primarily conducted through in-person exchanges, invited renowned experts in the field of lymphoid tumors from both domestic and international arenas. Through lectures, case discussions, and other forms of interaction, the forum focused on the latest achievements and advancements in the basic and clinical aspects of international lymphoid tumors. The goal was to further enhance the overall level of lymphoma diagnosis and treatment in China. At the conference, Professor Donglu Zhao from the Harbin Hematology and Oncology Research Institute gave a detailed presentation on the "CSCO Lymphoma Diagnosis and Treatment Guidelines — Interpretation of the Key Points of the Burkitt Lymphoma Guidelines." For a deeper understanding of this topic, "Oncology Frontier - Hematology Frontier" has compiled the content for readers' reference.1. Largest Real-World Study (RWS) of BL
A study by Andrew M. Evens et al., published in the 2021 BLOOD journal, represents the largest real-world study (RWS) of BL to date, collecting data from 702 newly diagnosed adult BL patients treated at 30 cancer centers in the United States from 2009 to 2018. After accounting for data loss due to missing follow-up information, 641 BL patients were included. The study aimed to analyze the differences in efficacy, survival impact, and prognostic factors of various treatment regimens for BL patients. The primary endpoints included progression-free survival (PFS), overall survival (OS), and treatment-related mortality (TRM). The results showed that the overall 3-year PFS and OS of BL patients after treatment were 64% and 70%, respectively.
Subgroup Analysis: There were no significant differences in PFS (P=0.220) and OS (P=0.390) among patients receiving the three main chemotherapy regimens (CODOX-M/IVAC, Hyper-CVAD/MA, and DA-EPOCH-R). Patients treated with rituximab had better survival rates than those who did not receive it (3-year PFS: 67% vs. 38%, P<0.001; 3-year OS: 72% vs. 44%, P<0.001).
Patients treated at academic hospitals had better survival rates than those treated at community hospitals (3-year PFS: 67% vs. 46%, P=0.006; 3-year OS: 72% vs. 53%, P=0.010).
Safety: The overall treatment-related mortality (TRM) was 10%, with common causes of death including infections (31 cases, 51%), gastrointestinal bleeding/perforation (9 cases, 15%), and respiratory failure (8 cases, 15%). Among the different treatment regimens, Hyper-CVAD/MA had the highest TRM at 11%, followed by DA-EPOCH (8%) and CODOX-M/IVAC (5%).
Prognostic Factors: Univariate analysis
showed that age ≥ 40 years, ECOG ≥ 2, advanced stage, bone marrow involvement, CNS involvement, LDH > 3×ULN, HB level < 11.5 g/dL, and ALB < 3.5 g/dL were adverse prognostic factors for PFS in adult BL patients. Multivariate analysis identified age ≥ 40 years, ECOG ≥ 2, LDH > 3×ULN, and CNS involvement as independent adverse prognostic factors (BL IPI).
2. NCI9177 Study
The 2020 JCO journal reported the results of the NCI9177 study, concluding that:
DA-EPOCH-R is safe and effective for both low-risk and high-risk patients. With a median follow-up of 58.7 months, the 4-year EFS for the overall population was 84.5% (95% CI: 76% ~ 90%), and the 4-year OS was 87.0% (95% CI: 79% ~ 92%). Among 15 low-risk patients, the 4-year EFS and OS were both 100%; among 98 high-risk patients, the 4-year EFS was 82.1% (95% CI: 73% ~ 89%), and the 4-year OS was 84.9% (95% CI: 76% ~ 91%).
DA-EPOCH-R was less effective for BL patients with CNS involvement. Under the BL-IPI model, the 5-year EFS for low-risk, intermediate-risk, and high-risk patients were 94.2%, 83.6%, and 66.7%, respectively. Regardless of risk level, patients with CNS/BM involvement had poorer prognosis compared to those without CNS/BM involvement.
3. HOVON/SAKK Study
In 2023, the Lancet Hematology journal published the follow-up results of the HOVON/SAKK study, which included 89 high-risk BL patients without CNS involvement from 2014 to 2021. A total of 84 patients were randomized (R-CODOX-M/R-IVAC group, n=43; DA-EPOCH-R group, n=41) with a median follow-up time of 19.1 months. The study aimed to evaluate the efficacy and safety of the two regimens. The results showed that for newly diagnosed high-risk BL patients without CNS involvement, DA-EPOCH-R had comparable efficacy to R-CODOX-M/R-IVAC but with less risk.
4. Research Progress on CAR-T±ASCT for R/R-BL Patients
A single-center study from China, published in the 2022 Front Immunol journal, evaluated the clinical efficacy and toxicity of CD19/CD22 CAR-T monotherapy (trial A) or combined with autologous stem cell transplantation (ASCT, trial B) in adult relapsed/refractory Burkitt lymphoma (R/R-BL) patients. A total of 28 R/R-BL patients were enrolled [trial A (n=15) and trial B (n=13)]. The results showed:
1. Overall population: 19 patients (67.9%) achieved an objective response rate (ORR), and 16 patients (57.1%) achieved complete remission (CR).
2. With a median follow-up of 12.5 months, 16 patients (trial A: 5 patients, trial B: 11 patients) survived, with estimated 1-year PFS and OS both at 55.6%. Trial B patients had significantly better 1-year PFS and OS than trial A patients.
3. Factors associated with achieving an objective response included TP53 mutation status, baseline LDH level, presence of bulky disease, and baseline ECOG score.
4. Adverse reactions: 2/4 grade CRS occurred in 39.3%, and ICANS in 10.7%.
Summary
1. BL is a highly aggressive NHL, often involving bone marrow and CNS. The c-MYC gene translocation is common, with 80% being t(8;14)(q24;q32), and Ki-67 above 95%. The BL-IPI prognostic assessment system helps risk stratification in adult patients, with poor prognosis for TP53-mutated patients.
2. BL patients are sensitive to chemotherapy, and rituximab combined with short-course, high-dose chemotherapy regimens has improved prognosis. Relapsed/refractory BL has a poor prognosis, and new drugs like CAR-T may offer new hope for these patients.
