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Background There is an absence of clinically relevant epidemiological data in regional Australia pertaining to haematological malignancies. Aim To determine the incidence and geographical variation of haematological malignancies in North Queensland using a clinically appropriate disease classification. Methods Retrospective, observational study of individual patient data records of all adults diagnosed with a haematological malignancy between 2005-2014 and residing within The Townsville Hospital Haematology catchment region. We report descriptive summaries, incidence rates and incidence-rate ratios of haematologic malignancies by geographic regions. Results 1581 haematological malignancies (69% lymphoid, 31% myeloid) were diagnosed over the 10-year study period. Descriptive data is presented for 58 major subtypes as per the WHO diagnostic classification of tumours of haematopoietic and lymphoid tissues. The overall median age at diagnosis was 66 years with a male predominance (60%). We demonstrate a temporal increase in the incidence of haematologic malignancies over the study period. We observed geographical variations in the age-standardised incidence rates per 100,000 ranging from 0.5 to 233.5. Our data suggests an increased incidence rate ratio for haematological malignancies in some postcodes within the Mackay area compared to other regions. Conclusion This study successfully reports on the incidence of haematological malignancies in regional Queensland using a clinically meaningful diagnostic classification system and identifies potential geographic hotspots. We advocate for such contemporary, comprehensive, and clinically meaningful epidemiological data reporting of blood cancer diagnoses in wider Australia. Such an approach will have significant implications toward developing appropriate data-driven management strategies and public health responses for haematological malignancies. This article is protected by copyright. All rights reserved.

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.