Loncastuximab tesirine in heavily pretreated patients with large B-cell lymphoma: a German Lymphoma Alliance analysis.

For patients with large B-cell lymphoma progressing after multiple lines of therapy few treatment options remain, including the new CD19-directed antibody-drug conjugate loncastuximab tesirine (lonca). To further elucidate its efficacy and safety, we conducted a real-world analysis including data from 31 German centers. Ninety-three heavily pre-treated patients received lonca in third and later line of therapy. 76% had received treatment with chimeric antigen receptor T-cells (n=55), bispecific antibodies (BsAbs) (n=56) or both (n=40). The overall response rate was 27% and complete response rate was 10%. Median progression-free (mPFS) and overall survival (mOS) were 2.2 and 4.4 months, respectively. Median PFS of responders was 11.4 months. Toxicity was acceptable, with grade ≥ 3 infections (13%) being the most common adverse event. Patients receiving subsequent allogeneic stem cell transplantation survived significantly better than the remaining non-consolidated patients (mOS: 15.2 vs. 3.8 months, p=0.048). In multivariable analysis, no response to the last therapy prior to lonca (OS - HR: 2.5, p=0.014) and secondary IPI (PFS/OS - HR: ≥2.0, p≤0.024) were significantly associated with poor outcomes. Lonca demonstrated a favorable safety profile with moderate efficacy in heavily pretreated patients. While enabling timely access to subsequent therapy, efficacy in earlier lines with combination partners may further increase response rates and durability of response.