Outcomes in patients (pts) with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL) treated with systemic therapy from real world experience (ORCHID) study.
Authors: Damaj Gandhi Laurent , Hampp Christian , Bachy Emmanuel , Prochazka Katharina , Jo Jae-Cheol , Kim Tae Min , Oberic Lucie , Townsend William , Jalbert Jessica J , Ma Qiufei , Kamat Siddhesh , Wang Joy , Ambati Srikanth R , Mohamed Hesham , Chaudhry Aafia , Thorley Eileen , Rippin Gerd , Harnett James , Thieblemont Catherine 
Published: June 2024

e19067

Background: Odronextamab, an off-the-shelf CD20×CD3 bispecific antibody, has shown compelling efficacy (objective response rate [ORR] 52%, complete response [CR] rate 31.5%) and a generally manageable safety profile in pts with heavily pretreated R/R DLBCL in the single-arm ELM-2 trial (NCT03888105; Ayyappan et al. ASH 2023). We evaluated outcomes in pts with R/R DLBCL treated with currently available third-line or later (3L+) therapies in a real-world setting (ORCHID; NCT05338892) to better evaluate results from ELM-2 in the absence of a randomized control arm. Methods: ORCHID is a multicenter, retrospective, observational study, using electronic medical record or research databases, of pts with R/R DLBCL who have received ≥2 prior lines of therapy (LoTs; including an anti-CD20 and an alkylator) and initiated 3L+ systemic therapy for DLBCL between January 1, 2015 and June 30, 2021. After applying similar eligibility criteria to those in the ELM-2 trial, inverse-probability of treatment weighting (IPTW) was used to balance key prognostic variables between the trial and real-world cohorts. Pts were followed from the start of qualifying LoT until death, end of study period (December 31, 2021), or loss to follow up, whichever occurred first. The primary endpoint was ORR per Lugano criteria assessed by independent central review (ICR). Secondary endpoints included ICR-assessed CR rate, disease control rate (DCR), progression-free survival (PFS), duration of response (DOR), and overall survival (OS) (see Thieblemont et al. ASH 2022). Results: Pts in ORCHID (N=148) generally had less severe disease than trial pts prior to IPTW. The most commonly used regimens were anti-CD20 based therapies, CAR T, and chemotherapy alone. The IPTW cohort had a median age 65 y, 79% Ann Arbor stage III/IV, 66% primary refractory, 88% refractory to last LoT, and median (range) prior LoT: 2 (2–6). In the IPTW cohort, ORR was 44%, CR 18%, and DCR 50%. Median (m) PFS (mPFS), DOR (mDOR), and OS (mOS) were 7.2, 9.0, and 10.8 mo, respectively. Given the lack of regular scans in routine practice (47% of pts had only one ICR response assessment over the study period), sensitivity analysis that considered subsequent treatment as progression resulted in shorter mPFS (4.6 mo) and mDOR (6.1 mo). In the majority of LoTs initiating non-CAR T therapy (n=111), ORR was 33%, CR 15%, DCR 43%. The mOS in non-CAR T group was 7.5 mo and was not reached in those intended for CAR T. Conclusions: Pts in the ORCHID study, especially those who did not receive CAR Ts, had markedly lower response rates than those in the R/R DLBCL cohort of ELM-2. Despite prior failure, most pts still received an anti-CD20 based regimen in 3L+ setting in routine practice, highlighting the need for treatment options with different mechanisms of action that provide deep and durable responses and improve outcomes in this pt population. Clinical trial information: NCT05338892 .