DOI: 10.4103/ijh.ijh_106_26 ISSN: 2072-8069

Frontline treatment strategies for diffuse large B-cell lymphoma-type Richter transformation from chronic lymphocytic leukemia: A systematic review

Ahmed Salleh Barefah
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BACKGROUND:

Diffuse large B-cell lymphoma (DLBCL)-type Richter transformation (RT) is the most common and most aggressive transformation of chronic lymphocytic leukemia. Frontline treatment is largely extrapolated from de novo DLBCL, although RT is biologically distinct and enriched for adverse genomic features.

OBJECTIVES:

To synthesize the evidence for frontline systemic therapy in DLBCL-type RT, separating treatment-naive cohorts from relapsed/refractory or mixed populations.

MATERIALS AND METHODS:

MEDLINE/PubMed, Embase, Cochrane CENTRAL, Web of Science, and major hematology congress proceedings were searched from inception through May 2026 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 and MOOSE guidance (PROSPERO CRD420261425279). Eligible studies enrolled adults with biopsy-confirmed DLBCL-type RT and reported a verifiable overall response rate (ORR). Proportions were pooled using the Freeman-Tukey transformation and DerSimonian–Laird random-effects models; leave-one-out and restricted maximum likelihood analyses assessed robustness. Risk of bias was appraised with the Newcastle–Ottawa and Joanna Briggs Institute tools.

RESULTS:

Sixteen studies/cohorts (approximately 510 patients) were included; seven were genuinely first-line. Pooled ORR was 48.8% (95% confidence interval [CI]:38.4%–59.2%; I 2 = 71.3%) across four first-line chemoimmunotherapy cohorts and 61.9% (95% CI: 50.4%–72.8%; I 2 = 0.0%) across three first-line venetoclax-or immune-based cohorts. Seven relapsed/refractory or mixed novel-agent cohorts yielded 52.1% (95% CI: 38.3%–65.8%; I 2 = 64.4%). Pooled estimates were stable on sensitivity analysis, but prediction intervals were wide. Six of 15 assessed studies were at low risk of bias.

CONCLUSION:

Conventional frontline chemoimmunotherapy for DLBCL-type RT remains unsatisfactory. First-line venetoclax-and immune-based combinations produced a higher pooled ORR, but this derives from three small uncontrolled trials and does not establish superiority. Biopsy confirmation, molecular characterization, trial enrollment, and early transplant referral for fit responders should be prioritized.

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