Polatuzumab vedotin (Pola) is an approved therapy in combination with rituximab and bendamustine for relapsed or refractory diffuse large B-cell lymphoma (RR-DLBCL) based on positive results of the landmark phase II randomised G029365 trial. However, trial results for many approved novel therapies in RR-DLBCL have not been replicated in routine care cohorts, as RR-DLBCL patient populations are heterogeneous and trial eligibility is increasingly restrictive. We evaluated outcomes from pola ± bendamustine and rituximab in patients with RR-DLBCL enrolled in a compassionate access program with no alternative treatment options identified via the Australasian Lymphoma and Related Diseases Registry according to their eligibility for the original phase II published study. Of 58 eligible patients, 74% met the criteria deeming them ineligible for the G029365 original study at the time of pola's commencement. Median progression-free survival and overall survival in our cohort were 2.3 and 3.5 months, respectively. In contrast to the landmark trial cohort, more of our patients ceased therapy prior to completion, the majority due to progressive disease and only 8/58 received any subsequent treatment. Dismal outcomes in this Australian real-world population demonstrate trial eligibility is challenging to meet, and newer treatments can be difficult to deliver in routine care. Clinically applicable results from therapeutic studies require trial cohorts to reflect representative clinical populations wherever possible, and more research is required to address the benefit of novel agents in the increasing majority who are ineligible for modern studies.

Topic: 19. Aggressive Non-Hodgkin lymphoma - Clinical 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 real-world 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. Aims: To describe outcomes of pts treated with compassionate access PolaBR for RRDLBCL in Australia. Methods: 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. Results: 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. 74% failed > 1 eligibility criteria of the landmark PolaBR study and 47% failed >2 ineligibility criteria (table 1). 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. Keywords: Diffuse large B cell lymphoma, relapsed/refractory, Relapsed lymphoma, Monoclonal antibody

BackgroundImmune thrombocytopenia (ITP) has been reported following COVID-19 vaccination. After index case fatalities, there was concern among patients both with and without a prior history of ITP in Australia.ObjectivesTo describe treatment outcomes of ITP after COVID-19 vaccination and compare relapsed vs historical pre-COVID-19 ITP cohorts.MethodsWe collected ITP cases in Australia within 6 weeks of receiving any COVID-19 vaccination as part of primary vaccination (up to October 17, 2021). Second, we reviewed platelet charts in a historical ITP cohort to determine whether platelet variability was distinct from relapsed ITP after vaccination.ResultsWe report on 50 patients (37 de novo, 13 relapsed ITP) vaccinated from March 22, 2021, to October 17, 2021. Although there was 1 fatality, bleeding was otherwise mostly minor: (70% WHO bleeding grade <2). De novo ITP was more likely after AstraZeneca ChAdOx1 nCoV-19 (89%) than Pfizer BNT162b2 (11%). Most patients responded quickly (median, 4 days; complete response, 40 of 45 [89%]). In the historical cohort, only 6 of 47 patients exhibited platelet variability (>50% decrease and platelets <100 × 109/L), but median platelet nadir was significantly higher than vaccination relapse (27 vs 6 × 109/L, P =.005).ConclusionITP was more frequently reported after AstraZeneca ChAdOx1 nCoV-19 than Pfizer BNT162b2 vaccination. Standard ITP treatments remain highly effective for de novo and relapsed ITP (96%). Although thrombocytopenia can be severe after vaccination, bleeding is usually mild. Despite some sampling bias, our data do not support a change in treatment strategies for patients with ITP after vaccination.

Background and Objectives Transfusion-associated circulatory overload is a leading cause of transfusion-related adverse events. The frequency and risks for transfusion-associated circulatory overload in ambulatory haematology patients are not known. Materials and Methods A retrospective cohort analysis of ambulatory patients transfused in a tertiary haematology centre, using medical records and an electronic transfusion database, was undertaken between January and December 2014. Variables studied included age, gender, diagnosis, heart failure, kidney disease and details of transfusions. Transfusion-associated circulatory overload was defined according to proposed International Society of Blood Transfusion criteria. Patients with clinical evidence of hypervolaemia, not meeting the TACO definition and/or who were prescribed otherwise unscheduled diuretic agent, were collectively deemed to be at 'risk of clinically significant hypervolaemia' (ROCSH). Results In the study period, 93 ambulatory patients (male = 49, female = 44, mean age = 75 center dot 89 +/- 11 center dot 37 years) attended 715 transfusion encounters, totalling 1536 packed red cell units. No cases of TACO occurred whilst 'ROCSH' events occurred in 57/715 (8%) of transfusion encounters. In a univariate model, age was significantly associated with 'ROCSH', odds ratio = 1 center dot 05 (P = 0 center dot 017 95%, CI 1 center dot 01-1 center dot 09) and no factors were significant on multivariate analysis. Conclusions Transfusion-associated circulatory overload occurs infrequently haematology patients receiving ambulatory blood transfusions. To our knowledge, this is the first study to report on occurrence and risk factors for circulatory overload in ambulatory transfusions. This study provides vital baseline data for future prospective studies on this important aspect of haemovigilance.

Introduction: Transfusion Associated Circulatory Overload (TACO) is a leading cause of transfusion related adverse events. Existing estimates of TACO incidence are derived from observations in a predominantly inpatient setting, where, incidence estimates range from 1 to 8% of transfusions (Bachowski G, et al. A Compendium of Transfusion Practice Guidelines Third Edition 2017: American Association Blood Banks). This is the first report of incidence and risk factors for TACO in ambulatory transfusions.