Outcomes of loncastuximab tesirine in heavily pretreated patients with diffuse large B-cell lymphoma, including the post-CAR T-cell therapy setting: A meta-analysis.

BACKGROUND

Loncastuximab tesirine, a CD19-directed antibody-drug conjugate, is a therapy for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), including after chimeric antigen receptor T-cell therapy. This study summarized efficacy and safety across published cohorts.

METHODS

The authors did a systematic review and meta-analysis of loncastuximab tesirine monotherapy in adults with relapsed or refractory DLBCL. They searched PubMed, Embase, and the Cochrane Library from inception to October 25, 2025, plus American Society of Hematology 2025 abstracts. They pooled single-arm proportions using random-effects proportional meta-analyses with Freeman-Tukey transformation and reconstructed individual patient data from Kaplan-Meier curves for time-to-event pooling (protocol: PROSPERO CRD420251156779). Seven studies (596 patients) met inclusion criteria.

RESULTS

Seven studies (596 patients) contributed to clinical outcomes across all analyses. Pooled overall response was 45.76% (95% CI, 28.75-63.28; I2 = 94.3%), and the complete response was 18.83% (95% CI, 10.60-28.70, I2 = 85.5%). Reconstructed data yielded a pooled median progression-free survival of 5.18 months (95% CI, 3.97-6.15) and median overall survival was 9.01 months (95% CI, 7.60-10.73; four studies). Among responders, median duration of response was 10.22 months (95% CI, 6.37-not estimable). Grade ≥3 thrombocytopenia, neutropenia and anemia occurred in 23.71%, 18.80%, and 11.01% of patients, respectively, and treatment discontinuation due to adverse events occurred in 12.61% (95% CI, 5.85-21.18).

CONCLUSIONS

Loncastuximab tesirine shows clinically meaningful activity in heavily pretreated R/R DLBCL, including post-CAR T-cell therapy settings, with frequent but manageable cytopenias. Pooled estimates showed substantial heterogeneity, driven mainly by real-world cohorts, and should be interpreted with caution.