Patients (pts) with large B-cell lymphoma (LBCL) relapsing or being refractory (r/r) following two prior systemic therapies are particularly difficult to treat. CD19-directed antibody-drug conjugate loncastuximab tesirine (lonca) represents one of the treatment options for these pts. In the LOTIS-2 trial lonca showed promising efficacy data with an overall response rate (ORR) of 48.3% and a complete response rate (CRR) of 24%. In the real-world setting in Europe, data on the efficacy and safety of lonca are scarce to date.

To assess the efficacy and feasibility of lonca we conducted a retrospective, multicenter analysis, enrolling 72 pts with r/r LBCL treated with lonca as a single agent in 24 centers from Germany.

We included de novo diffuse large B-cell lymphoma (DLBCL) (40/72), high grade B-cell lymphoma (HGBL) [(17/72; MYC & BCL2 rearrangements (11/17); not otherwise specified (NOS) (6/17)], transformed indolent lymphoma (14/72) and T-cell/histiocyte-rich large B-cell lymphoma (TCRLBCL) (1/72). Median age at lonca initation was 62 with almost equal gender distribution. Pts were heavily pretreated: 28 pts (38%) and 33 pts (46%) underwent lonca in forth line (4L) or later (5L+); only 11 pts (15%) received lonca in third line (3L). Seventy seven% pts were refractory to the last therapy prior lonca while 71% pts presented with IPI ≥ 3, 36% pts with bulky disease (≥ 7.5 cm) and 15% pts with ECOG 3-4 at lonca initiation. Of pts receiving lonca in 3L, 45% had bulky disease and IPI ≥ 3, 63% had a primary refractory or early relapsed disease after first line therapy. Finally, 43 pts (60%) had prior CAR-T treatment and 50 pts (69%) had prior bispecific antibodies (BsAb). Just 10% of pts (7/72) had no prior exposure to either CAR-T or BsAb. Of 72 pts, 20 received lonca with intent to consolidate with CAR-T cell therapy (14/20) or allogeneic stem cell transplantation (allo-SCT) (6/20).

Infections were documented in 31% of pts, with grades 3 in 13% of all pts. The incidence of liver enzyme elevation was 28% with only 1 grade 3 (1.3%). The frequency of edema was 13% with two pts suffering from grade 3. Skin reactions occurred in 14% of pts (all grades 1-2). Anemia, leukopenia and thrombocytopenia grade ≥3 were documented in 15%, 21% and 29% of pts, respectively.

Overall, 24% of pts responded to lonca, with 6% achieving CR and 18% partial response (PR). The ORR did not differ significantly in lonca administered in 3L, 4L, or 5L+: 18% vs. 21% vs. 27% (p=0.779). Similarly, ORR was 21% and 25% (p=0.728) in CAR-T naive/pretreated, and 23% and 24% (p=0.9) in BsAb naive/pretreated pts. Lonca was associated with numerically higher ORR in pts treated with intent to bridge (30% vs. 21%; p=0.429) and significantly higher in those pts (9/20) who underwent subsequent consolidation with CAR-T or allo-SCT: 56% vs. 20% without consolidation (p=0.017). The median progression-free survival (mPFS) was 2.1 months (mo), and the median overall survival (mOS) was 3.7 mo, while being significantly higher in responders (mPFS 7.2 mo; mOS 8.6 mo; p≤0.002 for both). Finally, pts achieving CR showed significantly higher PFS and OS rates than those in PR: mPFS 13.7 vs. 4.6 mo (p=0.037) and mOS 14.9 vs. 5.2 (p=0.012).

In the multivariate analysis, ECOG at lonca administration (PFS - [HR=2.09, p=0.042]) and LDH at the time of lonca considered as continuous variable (p=0.01 for OS) were the strongest predictors of survival after initiation of lonca.

In this real-world cohort representing a particularly difficult-to-treat population, with almost half of pts treated in 5L+, lonca as a single-agent showed a response rate of roughly 25% in r/r LBCL pts with a low CR rate due to a high proportion of pts who were high risk and heavily pretreated. The safety profile observed was consistent with known toxicities and was manageable in routine clinical practice with no new signals detected. Lonca is currently explored in earlier lines and in combination in ongoing clinical studies.

This content is only available as a PDF.
2025
Sign in via your Institution