P1132: long-term responses with loncastuximab tesirine: updated results from lotis-2, the pivotal phase 2 study in patients with relapsed/refractory diffuse large b-cell lymphoma

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical Background: Patients (pts) with diffuse large B-cell lymphoma (DLBCL) who relapse after stem cell transplant or chimeric antigen receptor therapy or are refractory to second-line therapy have poor prognosis and few treatment options (Chow et al. 2019). For these pts, long-term disease control with manageable toxicity is the goal. Loncastuximab tesirine (loncastuximab tesirine-lpyl; Lonca), an anti-CD19 antibody conjugated to a pyrrolobenzodiazepine dimer, demonstrated single-agent antitumor activity in LOTIS-2, the pivotal phase 2 study in heavily pretreated pts with relapsed/refractory (R/R) DLBCL (Caimi et al. 2021). In previously presented follow-up analyses (median follow-up: 7.8 months [mo; range: 0.3, 31.0]), durable responses to Lonca were observed (median duration of response [mDOR]: 13.4 mo; median duration of complete response [CR]: not reached [NR]; Zinzani et al. ICML 2021). Aims: To present updated long-term efficacy and safety from LOTIS-2 (NCT03589469) in pts with R/R DLBCL treated with Lonca, including subsets of pts with durable CR. Methods: LOTIS-2 was a multicenter, open-label, single-arm phase 2 study of Lonca monotherapy in pts with R/R DLBCL after ≥2 prior systemic therapies. Lonca was administered every 3 weeks (150 µg/kg for 2 cycles; 75 µg/kg thereafter). The primary efficacy endpoint was overall response rate (Lugano 2014 criteria). Secondary endpoints included DOR; CR rate; and relapse-free, progression-free (PFS; measured from start of therapy), and overall survival (OS). Efficacy and safety analyses were performed for all pts and subsets of pts with CR, and pts with CR who were event-free (no progressive disease or death) for ≥1 and ≥2 years (yr) from cycle 1, day 1. Results: As of final data cutoff (September 15, 2022; median follow-up: 7.8 mo [range: 0.3, 42.6]), 70 (48%) of 145 pts achieved response and 36 (25%) pts achieved CR; 16 (44%) and 11 (31%) of the 36 CR pts were event-free for ≥1 and ≥2 yr, respectively. Median numbers of doses were 12.5 and 13.0 for pts with CR who were event-free for ≥1 and ≥2 yr, respectively. All 11 pts with CR who were event-free for ≥2 yr were censored at study end. Among all pts, the mDOR was 13.4 mo (95% CI: 6.9, -), mPFS 4.9 mo (2.9, 8.3), and mOS 9.5 mo (6.7, 11.5). Among pts with CR, the mDOR, mPFS, and mOS were NR (Figure 1). All-grade treatment-emergent adverse events occurring in ≥30% of all pts were increased gamma-glutamyltransferase (42%), neutropenia (40%), and thrombocytopenia (33%). Summary/Conclusion: Among heavily pretreated pts in LOTIS-2, Lonca continued to demonstrate durable, long-term responses in pts with CR with a manageable safety profile; 31% of the 36 CR pts were event-free for ≥2 yr with no evidence of disease and no new anticancer therapy post-Lonca. Further study is needed to identify factors predictive of long-term response to Lonca. Funding: ADC Therapeutics SA; medical writing: CiTRUS Health Group.Keywords: Diffuse large B cell lymphoma, CD19, Long-term follow-up