Outcomes in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are poor. Loncastuximab- teserine (Lonca) is an antibody-drug conjugate which was approved by the Food and Drug Administration for the treatment of patients with R/R DLBCL who have received at least two prior lines of therapy, based on the results of the LOTIS-2 trial. However, there are limited data regarding its efficacy in the real-world setting. This retrospective study included 21 US centers and evaluated outcomes of patients with R/R DLBCL treated with Lonca. Our analysis comprises 187 patients with notably higher-risk baseline features compared to those of the LOTIS-2 population, including a higher proportion of patients with bulky disease (17% vs. 0%), high-grade B-cell histology (22% vs. 8%), and increased number of prior lines of therapy (median 4 vs. 3). The complete response rate was 14% and overall response rate was 32%. The median event-free survival and overall survival were 2.1 and 4.6 months, respectively. Those with bulky disease and high-grade B-cell histology had significantly worse outcomes, and those with non-germinal center cell of origin and a complete response to the most recent line of therapy demonstrated superior outcomes. In summary, in this largest retrospective cohort study of Lonca in the real-world setting, the response rates, event-free survival and overall survival were lower than those reported in LOTIS-2, which is likely reflective of its use in higher risk and more heavily pre-treated patients in the real world compared to the patients enrolled on a clinical study.

7542 Background: Brentuximab vedotin (BV) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is the new standard of care for newly diagnosed stage III/IV cHL. In the pivotal ECHELON-1 trial, peripheral neuropathy (PN) was the most common toxicity, seen in 67% of patients (pts) and leading to discontinuation of BV in 6.6%. However, PN from BV+AVD in cHL has not been studied in a non-trial setting, where clinicians may have different strategies for managing it. Methods: We conducted a multi-site, retrospective study to characterize PN in pts who were planned to receive 6 cycles of BV+AVD for newly diagnosed cHL before 9/2022. Data was obtained from medical records and PN was graded retrospectively using CTCAE v5.0 criteria. Multivariable logistic regression was used to assess factors associated with PN. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan Meier method. A Cox proportional hazards model was used to test the effect of discontinuation on PFS. Results: 153 pts from 10 US institutions were eligible. Median age was 35 years (range 18-76) with 22% of pts over 60 years old. Thirty-four pts (22%) had at least 1 ineligibility criteria for ECHELON-1, including stage (8% stage I/II), performance status (3% ECOG 3+), preexisting PN (6%), or other comorbidities including HIV and other malignancies (10%). Of advanced stage pts, 41% had IPS 4-7. Median no. BV+AVD cycles was 6 (range 1-6). PN was reported by 80% of pts during treatment; 39% experienced grade (G) 1, 31% G2, and 10% G3. In total, BV was modified in 44% of pts due to PN leading to BV discontinuation in 23% with median no. of doses omitted of 4 (range 1-10), dose reduction in 17% and temporary dose hold in 4%. Vinblastine was modified in 17% of pts due to PN including discontinuation or temporary hold in 10% and dose-reduction in 7%; in 35% of pts with vinblastine modification, BV was continued. None of the factors assessed (age, sex, baseline PN, diabetes mellitus) predicted development of any grade PN. However, higher initial dose of BV in mg (based on weight) was associated with increased risk of grade 2+ PN (OR 1.03, 95% CI 1.01-1.05, p = 0.002). With median follow up of 24 months (range 0.33-87), PN resolution was documented in 36% and improvement in 33% at last follow up. Ongoing G2+ PN was present in 13% of pts at last follow up. 2-year PFS for the advanced stage patients was 82.7% (95% CI 0.76-0.90) and OS was 97.4% (95% CI 0.944-1). Discontinuation of BV due to neuropathy did not affect PFS (HR 1.1, 95% CI 0.45-2.5). Conclusions: In the non-trial setting, BV+AVD was associated with a high incidence of PN. In our cohort, which includes pts who would not have been eligible for the pivotal ECHELON-1 trial, BV discontinuation rates were higher than previously reported, but 2-year outcomes remain comparable; discontinuation of BV was not associated with inferior PFS.