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Outcomes for marginal zone lymphoma (MZL) and follicular lymphoma (FL) remain suboptimal, owing to the limited number of approved agents and the incurable nature of the diseases. BGB-3111-AU-003 was a phase 1/2, open-label, multicenter, single-agent study of the selective Bruton's tyrosine kinase inhibitor zanubrutinib in 385 patients with B-cell malignancies. Here, we present safety and efficacy outcomes for the 53 enrolled patients with relapsed/refractory MZL (n = 20) and relapsed/refractory FL (n = 33), all of whom were enrolled during the Part 2 dose expansion, and therefore received zanubrutinib at the recommended phase 2 dose. Treatment with zanubrutinib was generally well tolerated, with most adverse events being <=grade 2. Atrial fibrillation/flutter was not reported. Two patients required dose reduction, and 4 patients discontinued treatment due to adverse events. Response was assessed by an independent review committee (IRC) for MZL and the investigators for FL, per Lugano 2014 classification for non-Hodgkin lymphoma. In patients with MZL, the overall response rate (ORR) was 80%, and complete response (CR) rate was 20%. With median follow-up of 33.8 months, median progression-free survival (PFS) was not reached. In patients with FL, the ORR was 36.4%, and the CR rate was 18.2%. After a median follow-up of 33.9 months, median PFS was 10.4 months. In conclusion, the results of this study suggest a favorable benefit-risk profile and support zanubrutinib as a potentially meaningful addition to available therapies for patients with relapsed/refractory MZL and FL. This study is registered on www.clinicaltrials.gov (NCT02343120).Copyright © 2022 American Society of Hematology.

Polatuzumab vedotin plus bendamustine and rituximab (pola+BR) received regulatory approvals in relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) based on primary results from the randomized arms of the GO29365 study. Following the randomized phase, 106 additional patients received pola+BR in a single-arm extension cohort. We report updated results from the randomized arms, and results of the extension cohort. In this phase Ib/II study, patients with R/R DLBCL who were transplant-ineligible received up to six 21-day cycles of pola+BR or BR. The primary endpoint of the randomized arms was complete response (CR) rate at end of treatment. Primary objectives of the extension cohort were safety, pharmacokinetics, and efficacy of pola+BR. As of July 7, 2020, 192 patients with R/R DLBCL were enrolled into pola+BR cohorts (n=152 [safety run-in: n=6; randomized: n=40; extension cohort: n=106]) or the BR cohort (n=40). Significant survival benefit with pola+BR versus BR persisted in the randomized arms (median progression-free survival [PFS]: 9.2 vs 3.7 months, hazard ratio [HR]: 0.42, 95% confidence interval [CI] 0.25-0.71 months; median overall survival [OS]: 12.4 vs 4.7 months, HR: 0.42, 95% CI 0.24-0.72 months). In the extension cohort, the independent review committee (IRC)-assessed objective response rate was 41.5% and CR rate was 38.7%; median IRC-assessed PFS and OS were 6.6 months and 12.5 months, respectively. No new safety signals with pola+BR were identified. Pola+BR is an effective treatment option for patients with R/R DLBCL, with a well-characterized and manageable safety profile. ClinicalTrials.gov: NCT02257567.Copyright © 2021 American Society of Hematology.

Introduction. Elderly patients (>60 years old) with Hodgkin lymphoma have inferior rates of survival compared to patients <60 years old due to multiple factors including treatment toxicity and comorbidities influencing the intensity of chemotherapy that can be successfully delivered. Hodgkin lymphoma is derived from germinal centre B-cells and contributed to by latent Epstein Barr Virus (EBV) infection in a number of patients. Aims. To examine the incidence and treatment outcomes of Bcell NHL following completion of treatment for CHL in elderly patients compared with younger patients. Methods. Adult patients diagnosed with CHL at our institutions from 2000-2015 were followed prospectively following initial treatment for survival and toxicity outcomes. Any subsequent diagnosis of B-cell NHL was confirmed by two expert lymphoma anatomical pathologists consistent with WHO 2008 diagnostic criteria. Results. 165 adult patients were available for analysis, of which 56 (34%) patients were >60 years old. There was no significant difference between elderly and young cohorts in the number of patients with early stage favourable, unfavourable or advanced stage CHL. Less elderly patients received ABVD-like chemotherapy (71% vs 95%). There was a higher number of relapses of CHL in elderly patients (31% vs 20%). At a median follow-up of surviving patients at 2.7 years, there was a much higher incidence of secondary malignancy in elderly patients n=11 vs n=2 (24% vs 2%), of which there were far more haematological compared to solid malignancies n=8 (17%) vs n=3 (6%). Specific histologies included Diffuse Large B-cell Lymphoma (5), Follicular lymphoma (1), Lymphoplasmacytic lymphoma (1) and Chronic lymphocytic leukaemia (1). Patients with DLBCL were treated with R-CEOP and resulted in 2 patients achieving long-term relapse free survival. Conclusions. There is a high incidence of B-cell NHL in elderly patients with CHL, suggestive of a common germinal centre derived progenitor cell

Introduction: While the majority of patients with DLBCL can expect to be cured with R-CHOP chemotherapy, the outcome for those with R-IPI >= 3 is poor with approximately 50% eventually succumbing to progressive lymphoma. Dose-intense regimens have failed to improve outcomes for the majority mainly due to toxicity. Since 2007, our centre has been consolidating poor risk patients with 2 cycles of systemic R-HD-MTX for the purpose of CNS prophylaxis. Aim(s): The purpose of this study was to examine the effect of R-HD-MTX following completion of R-CHOP on overall survival (OS), progression-free survival (PFS) and CNS relapse in patients with R-IPI >=3 DLBCL. Method(s): Patients with DLBCL and R-IPI >= 3 in remission after R-CHOP were included in the study. Patients receiving HD-MTX were compared with an historical cohort that received otherwise similar therapy. Cell of origin was performed by IHC according to Choi in 54 cases. Survival correlates were analysed by Cox regression using SPSS. Result(s): One hundred four patients with newly diagnosed DLBCL and an R-IPI >= 3 completed R-CHOP-like chemotherapy. Forty-two patients received 2 cycles of HDMTX 3 g/m2 with rituximab. Patients receiving HD-MTX were younger (median age 67 v. 72 yrs), though the proportion over 60 yrs (HD-MTX 76% v. standard 85%), proportion with advanced stage (98% v. 87%) and raised LDH (86% v. 74%) were similar. At a median follow-up of surviving patients at 2.6 years, patients who received HDMTX had improved 2-year OS (84% v. 66%, HR 0.47, P = 0.06) and PFS (81% v. 56%, HR 0.46, P = 0.02). This was attributable to a reduction in the 2-year systemic relapse rate (19% v. 32% (HR 0.49, P = 0.07) and CNS relapse rate 3% v. 15% (HR 0.42, P = 0.15). The benefit of HD-MTX was only seen in GCB phenotype (PFS 88% v. 50%, (HR 0.25, P = 0.04) cf ABC phenotype 63% v. 57% (HR 0.83 P = 0.92). The regimen was well tolerated with no severe toxicity. Conclusion(s): The use of consolidative R-HD-MTX is associated

Summary: Lumiliximab is a chimeric monoclonal antibody that targets CD23 on the surface of chronic lymphocytic leukaemia (CLL) B-cells. Early phase clinical studies with lumiliximab alone and in combination with fludarabine, cyclophosphamide and rituximab (FCR) established its potential efficacy and tolerability. The 152CL201 trial [Lumiliximab with fludarabine, cyclophosphamide and rituximab (FCR) versus FCR alone in subjects with relapsed CLL; LUCID] was a phase 2/3, randomized (1:1), open-label, multicentre study of lumiliximab in combination with FCR versus FCR alone in patients with relapsed CLL. Six hundred and twenty-seven patients were randomized to either arm. Overall the combination of lumiliximab with FCR was not significantly better than FCR alone (overall response rate 71% vs. 72%, complete response rate 16% vs. 15%, median progression-free survival 24.6 vs. 23.9 months respectively, for FCR with and without lumiliximab). There was a slightly increased incidence of adverse events with lumiliximab but these increases did not appear to lead to differences in eventual outcomes. An interim analysis failed to show sufficient efficacy of the combination of lumiliximab with FCR. The study was therefore stopped early for lack of efficacy. Despite the eventual outcome, the LUCID trial is one of the largest studies that provides valuable insight into the efficacy and tolerability of FCR as a therapeutic option for patients with relapsed CLL.Copyright © 2014 John Wiley & Sons Ltd.

Background:While the majority of patients with Diffuse large B-cell lymphoma (DLBCL) can expect to be cured with R-CHOP chemotherapy, the outcome for patients with poor risk disease is less certain with approximately 50% of patients eventually succumbing to their disease. Dose intense regimens have largely failed to improve outcomes, and are associated with increased toxicity. However certain regimens may have a role in younger poor risk patients. The association of poor-risk disease with central nervous system (CNS) recurrence has led many centres to advocate the use of systemic high-dose methotrexate (HD-MTX) consolidation in poor-risk patients. Since 2007 our centre has been consolidating patients deemed to be at high-risk of CNS recurrence including those with IPI>=3, involvement of a high-risk site (testis, ovary, breast, kidney, extradural or skin) or those with two involved extra nodal sites and a raised lactate dehydrogenase with two cycles of intravenous methotrexate 3g/m2 and rituximab 375mg/m2 following the completion of RCHOP. HD-MTX is only administered to patients in CR after completion of RCHOP with adequate performance status. Aim(s): In this study we examine the effect of HD-MTX on overall survival (OS) and Progression Free Survival (PFS) in patients with poor-risk DLBCL. Method(s): Patients were included in the study if they had DLBCL diagnosed according to WHO 2008 criteria, an R-IPI >= 3, received two or more cycles of R-CHOP-like chemotherapy, and had adequate clinical information that included baseline clinical characteristics, treatment regimens and clinical outcome. Patients were excluded if they were too frail to receive chemotherapy or failed to achieve a CR following R-CHOP therapy. A total of 92 patients met the entry criteria of which 17 received HD-MTX. Survival correlates were analysed by Cox regression using SPSS. Result(s):While patients receiving HD-MTX were younger (median age 69 v. 74), the proportion over 60 years was similar in

Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a devastating complication; the optimal prophylactic strategy remains unclear. We performed a multicentre, retrospective analysis of patients with DLBCL with high risk for CNS relapse as defined by two or more of: multiple extranodal sites, elevated serum LDH and B symptoms or involvement of specific high-risk anatomical sites. We compared three different strategies of CNS-directed therapy: intrathecal (IT) methotrexate (MTX) with (R)-CHOP 'group 1'; R-CHOP with IT MTX and two cycles of high-dose intravenous (IV) MTX 'group 2'; dose-intensive systemic antimetabolite-containing chemotherapy (Hyper-CVAD or CODOXM/IVAC) with IT/IV MTX 'group 3'. Overall, 217 patients were identified (49, 125 and 43 in groups 1-3, respectively). With median follow-up of 3.4 (range 0.2-18.6) years, 23 CNS relapses occurred (12, 10 and 1 in groups 1-3 respectively). The 3-year actuarial rates (95% CI) of CNS relapse were 18.4% (9.5-33.1%), 6.9% (3.5-13.4%) and 2.3% (0.4-15.4%) in groups 1-3, respectively (P=0.009). The addition of high-dose IV MTX and/or cytarabine was associated with lower incidence of CNS relapse compared with IT chemotherapy alone. However, these data are limited by their retrospective nature and warrant confirmation in prospective randomised studies.

Introduction. Despite favourable outcomes with chemoimmunotherapy for the majority of patients with diffuse large B-cell lymphoma (DLBCL), approximately one-third of patients experience relapsed or refractory disease portending poor prognosis. Patients ineligible for treatment intensification with salvage chemotherapy may be offered palliative chemotherapy or radiotherapy, and in the setting of single-site progression, salvage radiotherapy with curative intent. There remains a paucity of evidence for the latter with no randomised clinical trials or large series reported in the literature. The study was conducted to assess the outcomes of patients treated with salvage radiotherapy for limited stage relapsed / refractory DLBCL (rrDLBCL) at Monash Health, Australia, to determine its utility and inform future treatment algorithms. Methods. DLBCL cases (867 patients) diagnosed per WHO criteria at Monash Health, Melbourne, Australia, between 1996-2019 within the Haematology Database were analysed. Adult patients with rrDLBCL (including transformed indolent lymphoma) treated with salvage radiotherapy alone with curative intent were included in the study. Patients with inadequate clinical information or follow up data available or those in whom radiotherapy was administered as consolidation or clearly palliative intent were excluded. Results. From January 1996-December 2019, 18 eligible patients were identified for inclusion in the study (12 refractory and 6 relapsed). A further 14 patients were excluded due to radiotherapy for clearly palliative intent (n = 7), CNS relapse (n = 5), consolidation (n = 1) or prior indolent lymphoma (n = 1). Median age at radiotherapy commencement for the study population was 71 years (range 42-83). 11/18 had biopsy-proven refractory disease, a further 3/18 had inconclusive biopsy with high suspicion of active disease on imaging and remaining patients were treated on basis of high clinical suspicion from PET imaging with sites not amenable to

Introduction. Despite favourable outcomes with chemoimmunotherapy for the majority of patients with diffuse large B-cell lymphoma (DLBCL), approximately one-third of patients experience relapsed or refractory disease portending poor prognosis. Patients ineligible for treatment intensification with salvage chemotherapy may be offered palliative chemotherapy or radiotherapy, and in the setting of single-site progression, salvage radiotherapy with curative intent. There remains a paucity of evidence for the latter with no randomised clinical trials or large series reported in the literature. The study was conducted to assess the outcomes of patients treated with salvage radiotherapy for limited stage relapsed / refractory DLBCL (rrDLBCL) at Monash Health, Australia, to determine its utility and inform future treatment algorithms. Methods. DLBCL cases (867 patients) diagnosed per WHO criteria at Monash Health, Melbourne, Australia, between 1996-2019 within the Haematology Database were analysed. Adult patients with rrDLBCL (including transformed indolent lymphoma) treated with salvage radiotherapy alone with curative intent were included in the study. Patients with inadequate clinical information or follow up data available or those in whom radiotherapy was administered as consolidation or clearly palliative intent were excluded. Results. From January 1996-December 2019, 18 eligible patients were identified for inclusion in the study (12 refractory and 6 relapsed). A further 14 patients were excluded due to radiotherapy for clearly palliative intent (n = 7), CNS relapse (n = 5), consolidation (n = 1) or prior indolent lymphoma (n = 1). Median age at radiotherapy commencement for the study population was 71 years (range 42-83). 11/18 had biopsy-proven refractory disease, a further 3/18 had inconclusive biopsy with high suspicion of active disease on imaging and remaining patients were treated on basis of high clinical suspicion from PET imaging with sites not amenable to