POLATUZUMAB, BENDAMUSTINE & RITUXIMAB (POLA-BR) EFFICACY IN RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA (RRDLBCL) TRIAL-INELIGIBLE PATIENTS: AN AUSTRALIAN LYMPHOMA REGISTRY (LARDR) STUDY.

Abstract

Background: RRDLBCL outcomes remain poor despite autologous transplant and CAR-T therapies offering potential cure to a minority. Evidence for current therapies is mostly from phase II trials with stringent eligibility criteria. Applicability to realworld populations is poorly understood. PolaBR efficacy in RR DLBCL was shown in the landmark GO29365 study (BCT02600897; Sehn Blood Adv 2022). However, the efficacy of PolaBR in routine care RR DLBCL patients (pts) who fail to meet original study eligibility criteria is unknown. Here we report outcomes of Australian RR DLBCL pts receiving compassionate PolaBR according to their eligibility for the GO29365 trial. Aim(s): To describe outcomes of pts treated with compassionate access PolaBR for RRDLBCL in Australia. Method(s): This was a retrospective study of RR DLBCL pts >=18y receiving Pola+/-BR from the Australian Lymphoma Registry (LaRDR). Data analysed included: demographics, pt demographics, disease & prior therapy details, trial eligibility criteria, outcomes and toxicity. Descriptive statistics were used to report frequency. Kaplan-Meier method and the Cox proportional hazard model were used for comparison of survival & comparisons according to prognostic factors. Result(s): 58 pts were identified between 2019-2022, median age 63.0y, 62% were male; 86% had stage III-IV disease; 61% had R-IPI >3. 70% had >=2 prior therapies (38% >3 prior lines) with most treatment lines being chemotherapy with rituximab. Pola was given with BR in 59%, Ritux only in 24%; and single-agent in 8%. Just 27% completed all 6 planned cycles. Reasons for cessation included progressive disease 52%; bridging to other therapy 10%; death 6%; toxicity 4%. 8 pts received up to 2 subsequent lines of therapy, with 2 receiving CAR-T therapy. Overall response rate was 38% (25% CR). Median follow up was 3.2m (range 0-31). Median overall survival was 3.9m (95% CI 2.9-7.3m). Median PFS was 2.5m (95% CI 1.9-4.1m). No difference in OS or PFS was observed for eligible vs non-eligible pts and failure of any one eligibility criteria category did not impact outcome. No difference in OS observed between pola-BR and pola-R (p=0.32). Summary/Conclusion: While response rates were similar to other real-world studies (Northend et al 2022; Dimou et al 2021; Wang et al 2022) they were lower than the registration trial. The high proportion of pts ineligible for the landmark pola-BR registration study and limited access to subsequent therapy potentially explain inferior response and survival outcomes in our cohort. Although acknowledging our modest sample size impacts the results, outcomes of novel therapies in real-world pts are likely influenced by factors outside of those related to trial eligibility such as adverse disease biology and additional comorbidites. .