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Background Lymphoma is a malignancy of lymphocytes and lymphoid tissues comprising a heterogeneous group of diseases, with up to 80 entities now described. Lymphoma is the 6th most common cancer in Australia, affecting patients of all ages, with rising incidence rates. With the proliferation of efficacious novel agents, therapeutic strategies are increasingly diverse and survival is improving. There is a clear need for contemporary robust and detailed data on diagnostic, investigational and management strategies for this disease in Australia, New Zealand and worldwide, to inform and benchmark local and international standards of care. Clinical quality registries can provide these data, and support development of strategies to address variations in management, including serving as platforms for clinical trials and research. The Lymphoma and Related Diseases Registry (LaRDR) was developed to capture details of patient demographics, disease characteristics, and management throughout their disease course and therapy and to develop outcome benchmarks nationally and internationally for lymphoma. This report describes the aims, development and implementation of the LaRDR, as well as challenges addressed in the process.Methods The LaRDR was established in 2016 as a multicentre, collaborative project at sites across Australia with a secure online database which collects prospective data on patients with a new diagnosis of lymphoma or chronic lymphocytic leukaemia (CLL). LaRDR development required multidisciplinary participation including specialist haematology, information technology, and biostatistical support, as well as secure funding. Here we describe the database development, data entry, ethics approval process, registry governance and support for participating sites and the coordinating centre.Results To date more than 4,700 patients have been enrolled from 27 sites. Multiple challenges arose during the development, which we describe, along with approaches used to overcome them. Several confirmed international collaborations are now in place, and the registry is providing valuable data for clinicians, researchers, industry and government, including through presentations of results at major national and international conferences.Conclusion Challenges in establishing the LaRDR have been successfully overcome and the registry is now a valuable resource for lymphoma clinicians, researchers, health economists and others in Australia and globally.

Monitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level

Background Graft-versus-myeloma (GvM) effect from allogeneic-SCT potentially affords long-term disease control in multiple myeloma (MM). A salvage program incorporating chemotherapy followed by tandem autologous + non-myeloablative allogeneic-SCT (TAA-SCT) may offer a survival advantage over chemotherapy alone (ChA) Method Consecutive patients with relapsed MM (R-MM) salvaged with chemotherapy followed by TAA-SCT at the Alfred between Jan-08 and Dec-19 were identified. A 2:1 comparator cohort salvaged with ChA (iMiD agent/PI available) matched for age/sex/ISS-stage, was extracted from the Myeloma and Related Diseases Registry (MRDR). All patients received autologous-SCT as part of their upfront treatment. Survival was assessed by Kaplan-Meier method and compared using log-rank test. Prognostic variables were adjusted using Cox-regression. Results 48 patients received TAA-SCT following salvage chemotherapy during the study period; 35% met criteria for high-risk myeloma at diagnosis (ISS-III and/or adverse CG/FISH) with a median age at salvage of 57 [range: 32-68] and 2 prior therapy lines [range: 1-7]. Preceding TAA-SCT, salvage chemotherapy yielded ≥ PR in ~95% of cases; iMiD® and/or PI were used in ~85%. 87 matched patients were identified from the MRDR as the ChA cohort. Baseline characteristics were comparable, except that the TAA-SCT cohort was more heavily pre-treated (p Conclusion In the iMiD® and PI era, TAA-SCT following chemotherapy remains an effective salvage strategy in selected patients with R-MM, providing an immunological platform for a GvM effect with OS and PFS advantage over chemotherapy alone.

Background Transformation of Chronic Lymphocytic Leukaemia (CLL) or Small Lymphocytic Lymphoma (SLL) to high-grade disease (Richter's Transformation; RT) carries a poor prognosis. Despite the advent of novel therapies, published data indicates that chemoimmunotherapy remains the standard of care for RT. This project evaluated real-world outcomes in patients with RT across eight Australian centres to validate known prognostic factors, as well as identify new predictors of survival in this cohort of patients. Our aims were also to determine if prior BTK inhibitors (BTKi), BCL 2 inhibitors (BCL2i), or escalation of treatment regimen impacted these patients' outcome. Methods This was a retrospective multicentre study conducted by members of the Australasian Lymphoma Alliance in 8 centres across 4 Australian states. Consecutive patients with biopsy proven Diffuse Large B-Cell Lymphoma (DLBCL) or Hodgkin Lymphoma (HL) type RT between 2010 and 2019 were identified using institutional databases. Patients' diagnoses were confirmed by review of local pathology reports. Patients' characteristics, treatment received, and outcomes were recorded and analysed. Univariate comparisons were made using Cox regression analysis. Kaplan Meier curves were used for analysis of overall survival (OS) measured from diagnosis of high-grade disease. Results Seventy-eight patients (55 with CLL and 23 with SLL) were included in the analysis. The majority had low Rai stage at diagnosis (stage 0 in 41% of patients, 1 in 39%, 2 in 16%, 3 in 3%, and 4 in 1%). 25% had prior treatment of low-grade disease with a BTKi and 18% with a BCL2i. At the time of low-grade diagnosis, 54/78 (69%) of patients (pts) had had mutational analysis: 24% (13/54) had a 17p deletion, 78% (17/22) were IgHv unmutated, and 33% (6/18) had a TP53 mutation. Median time to transformation from CLL diagnosis was 4.8 years (range 0-24). 42% had received 2 prior lines of treatment for CLL/SLL at the time of transformation (range 0-5). The predominant histology was DLBCL (71 pts with DLBCL; 6 pts with HL, 1 pt had HL and DLBCL concurrently). Majority of the pts had ECOG1.5x ULN) (HR 3.0; CI 1.6-5.8), 17p deletion (HR 2.34; CI 1.12-4.91), or bone marrow involvement by high grade disease (HR 2.99; CI 1.5-5.9) had an inferior OS. Prior low-grade treatment with a BTKi (HR 1.67; CI 0.88-3.18) or a BCL2i (HR 1.79; CI 0.92-3.45) did not impact outcome following transformation. Conclusions This is the largest Australian report on patient outcome following RT. Whilst prior CLL treatment was associated with worse outcome after transformation, prior BTKi or BCL2i use did not seem to have an impact on survival. Furthermore, elevated LDH >1.5 ULN and bone marrow involvement with RT were also predictors of poor patient outcome, with the latter not previously described. Finally, intensive chemotherapy regimens were found not to be superior to R-CHOP chemotherapy, suggesting that RCHOP remains the treatment of choice in this population. The OS for patients with RT is poor, and research into more effective therapies is needed. Figure 1 Figure 1. Disclosures Lewis: Roche: Consultancy, Honoraria; Janssen: Honoraria, Patents & Royalties: Conference attendance; Novartis: Patents & Royalties: Conference attendance; AstraZeneca: Consultancy, Honoraria. Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Tam: Beigene: Research Funding; Janssen: Research Funding; Abbvie: Research Funding; Loxo: Honoraria; Beigene: Honoraria; Janssen: Honoraria; Abbvie: Honoraria. Opat: Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astra Zeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Research Funding; Sandoz: Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees; Monash Health: Current Employment; Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cheah: Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding; Lilly: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; MSD: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Ascentage Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; TG therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Ku: Roche: Consultancy; Antegene: Consultancy; Genor Biopharma: Consultancy.

Acute monocytic leukaemia (French-British-American classification: AML-M5b) is characterised by a predominance of cells of the monocytic lineage on bone marrow examination. Furthermore, a discerning feature is its tendency for tissue infiltration. While gum hypertrophy and hepatosplenomegaly are common, ocular involvement is rare. Here, we present a case of a 75-year-old man referred with proptosis and monocytosis—subsequently diagnosed as AML-M5b, whose disease course was distinguished by extensive tissue invasion (ocular, pulmonary, liver, spleen). Cytogenetics and molecular tests were consistent with blastic transformation of previously undiagnosed chronic myelomonocytic leukaemia, supported by the presence of long-standing, low-grade monocytosis. Notably, a BRAF V600E mutation was also detected—an oncogenic driver previously reported in de novo and therapy-related, but not chronic myelomonocytic leukaemia-transformed, AML-M5b. While an initial response to cytoreductive treatment was observed, his tissue-invasive disease soon progressed with worsening pulmonary infiltrates, disseminated intravascular coagulation and renal failure, resulting in death.