Induction treatment in high-grade B-cell lymphoma with a concurrent MYC and BCL2 and/or BCL6 rearrangement: a systematic review and meta-analysis

Vanja Zeremski; Siegfried Kropf; Michael Koehler; Niklas Gebauer; Ellen D McPhail; Thomas Habermann; Francesca Schieppati; Dimitrios Mougiakakos

doi:10.3389/fonc.2023.1188478

Induction treatment in high-grade B-cell lymphoma with a concurrent MYC and BCL2 and/or BCL6 rearrangement: a systematic review and meta-analysis

Front Oncol. 2023 Jul 20:13:1188478. doi: 10.3389/fonc.2023.1188478. eCollection 2023.

Authors

Vanja Zeremski¹, Siegfried Kropf², Michael Koehler^{1

3}, Niklas Gebauer⁴, Ellen D McPhail⁵, Thomas Habermann⁶, Francesca Schieppati⁷, Dimitrios Mougiakakos¹

Affiliations

¹ Department of Hematology and Oncology, Medical Center, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
² Department for Biometry and Medical Informatics, Otto-von-Guericke University Magdeburg, Magdeburg, Germany.
³ Specialty Practice for Psycho-Oncology, Magdeburg, Germany.
⁴ Department of Hematology and Oncology, University Hospital of Schleswig-Holstein, Luebeck, Germany.
⁵ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, United States.
⁶ Division of Hematology, Mayo Clinic, Rochester, MN, United States.
⁷ Hematology, ASST Spedali Civili di Brescia, Lombardy, Italy.

Abstract

Background and aim: High-grade B cell lymphomas with concomitant MYC and BCL2 and/or BCL6 rearrangements (HGBCL-DH/TH) have a poor prognosis when treated with the standard R-CHOP-like chemoimmunotherapy protocol. Whether this can be improved using intensified regimens is still under debate. However, due to the rarity of HGBCL-DH/TH there are no prospective, randomized controlled trials (RCT) available. Thus, with this systematic review and meta-analysis we attempted to compare survival in HGBCL-DH/TH patients receiving intensified vs. R-CHOP(-like) regimens.

Methods: The PubMed and Web of Science databases were searched for original studies reporting on first-line treatment in HGBCL-DH/TH patients from 08/2014 until 04/2022. Studies with only localized stage disease, ≤10 patients, single-arm, non-full peer-reviewed publications, and preclinical studies were excluded. The quality of literature and the risk of bias was assessed using the Methodological Index for Non-Randomized Studies (MINORS) and National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Random-effect models were used to compare R-CHOP-(like) and intensified regimens regarding 2-year overall survival (2y-OS) and 2-year progression-free survival (2y-PFS).

Results: Altogether, 11 retrospective studies, but no RCT, with 891 patients were included. Only four studies were of good quality based on aforementioned criteria. Intensified treatment could improve 2y-OS (hazard ratio [HR]=0.78 [95% confidence interval [CI] 0.63-0.96]; p=0.02) as well as 2y-PFS (HR=0.66 [95% CI 0.44-0.99]; p=0.045).

Conclusions: This meta-analysis indicates that intensified regimens could possibly improve 2y-OS and 2y-PFS in HGBCL-DH/TH patients. However, the significance of these results is mainly limited by data quality, data robustness, and its retrospective nature. There is still a need for innovative controlled clinical trials in this difficult to treat patient population.

Systematic review registration: https://www.crd.york.ac.uk/prospero, identifier CRD42022313234.

Keywords: double-hit lymphoma (DHL); high-grade B cell lymphoma; induction treatment; meta-analysis; triple-hit lymphoma (THL).

Publication types

Systematic Review

Grants and funding

TH reported funding by MER P50 CA97274.