Epworth Collection: Epworth Centre for Immunotherapies and Snowdome LaboratoriesEpworth Centre for Immunotherapies and Snowdome Laboratorieshttp://hdl.handle.net/11434/20282024-03-28T19:15:28Z2024-03-28T19:15:28ZThe Integration of Biobanking as standard practice across a range of haematological malignancies in the Australian private healthcare setting.Petley, EmmaNguyen-Ngo, CaitlynBrooks, NicoleJohnston, HayleyTan, CharmaineHappell, GretelRamnarain, JaiPrince, H MilesYannakou, Costashttp://hdl.handle.net/11434/21542022-10-06T10:02:58Z2022-10-01T00:00:00ZTitle: The Integration of Biobanking as standard practice across a range of haematological malignancies in the Australian private healthcare setting.
Epworth Authors: Petley, Emma; Nguyen-Ngo, Caitlyn; Brooks, Nicole; Johnston, Hayley; Tan, Charmaine; Happell, Gretel; Ramnarain, Jai; Prince, H Miles; Yannakou, Costas
Abstract: Biobanks are essential tools for researching risk factors that underlie complex diseases, including cancer The
Molecular Oncology and Cancer Immunology (MOCI) Biobank Study at Epworth HealthCare is a repository of
biospecimens and clinical information of participants from a variety of clinical backgrounds The primary aim of this study is to maintain a resource to facilitate ethically approved research studies to discover new ways to treat, monitor and prevent diseases with the overarching goal of developing a foundation for improved personalised medicine.2022-10-01T00:00:00ZIsatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma: follow-up analysis of the Phase 3 ICARIA-MM study.Prince, Henry Mileshttp://hdl.handle.net/11434/21262023-07-31T04:44:40Z2022-03-23T00:00:00ZTitle: Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in relapsed and refractory multiple myeloma: follow-up analysis of the Phase 3 ICARIA-MM study.
Epworth Authors: Prince, Henry Miles
Abstract: Abstract
Background: The primary analysis of the ICARIA-MM study showed significant improvement in progression-free survival with addition of isatuximab to pomalidomide-dexamethasone in relapsed and refractory multiple myeloma. Here, we report a prespecified updated overall survival analysis at 24 months after the primary analysis.
Methods: In this randomised, multicentre, open-label, phase 3 study adult patients (aged ≥18 years) with relapsed and refractory multiple myeloma who had received at least two previous lines of therapy, including lenalidomide and a proteasome inhibitor, and had an Eastern Cooperative Oncology Group performance status of 0-2 were recruited from 102 hospitals in 24 countries across Europe, North America, and the Asia-Pacific regions. Patients were excluded if they had anti-CD38 refractory disease or previously received pomalidomide. Patients were randomly assigned (1:1), using an interactive response technology with permuted blocked randomisation (block size of four) and stratified by number of previous treatment lines (2-3 vs >3) and aged (<75 vs ≥75 years), to isatuximab-pomalidomide-dexamethasone (isatuximab group) or pomalidomide-dexamethasone (control group). In the isatuximab group, intravenous isatuximab 10 mg/kg was administered on days 1, 8, 15, and 22 of the first 4-week cycle, and then on days 1 and 15 of subsequent cycles. Both groups received oral pomalidomide 4 mg on days 1-21 of each cycle, and weekly oral or intravenous dexamethasone 40 mg (20 mg if aged ≥75 years) on days 1, 8, 15, and 22 of each cycle. Treatment was continued until disease progression, unacceptable toxicity, or withdrawal of consent. Here' we report a prespecified second interim analysis of overall survival (time from randomisation to any-cause death), a key secondary endpoint, in the intention-to-treat population (ie, all patients who provided informed consent and allocated a randomisation number) at 24 months after the primary analysis. Safety was assessed in all patients who received at least one dose or part dose of study treatment. The prespecified stopping boundary for the overall survival analysis was when the derived p value was equal to or less than 0·0181. This study is registered with ClinicalTrials.gov, NCT02990338, and is active, but not recruiting.
Findings: Between Jan 10, 2017, and Feb 2, 2018, 387 patients were screened and 307 randomly assigned to either the isatuximab (n=154) or control group (n=153). Median follow-up at data cutoff (Oct 1, 2020) was 35·3 months (IQR 33·5-37·4). Median overall survival was 24·6 months (95% CI 20·3-31·3) in the isatuximab group and 17·7 months (14·4-26·2) in the control group (hazard ratio 0·76 [95% CI 0·57-1·01]; one-sided log-rank p=0·028, not crossing prespecified stopping boundary). The most common grade 3 or worse treatment-emergent adverse events in the isatuximab group versus the control group were neutropenia (76 [50%] of 152 patients vs 52 [35%] of 149 patients), pneumonia (35 [23%] vs 31 [21%]), and thrombocytopenia (20 [13%] vs 18 [12%]). Serious treatment-emergent adverse events were observed in 111 (73%) patients in the isatuximab group and 90 (60%) patients in the control group. Two (1%) treatment-related deaths occurred in the isatuximab group (one due to sepsis and one due to cerebellar infarction) and two (1%) occurred in the control group (one due to pneumonia and one due to urinary tract infection).
Interpretation: Addition of isatuximab plus pomalidomide-dexamethasone resulted in a 6·9-month difference in median overall survival compared with pomalidomide-dexamethasone and is a new standard of care for lenalidomide-refractory and proteasome inhibitor-refractory or relapsed multiple myeloma. Final overall survival analysis follow-up is ongoing.
Funding: Sanofi.
Description: Randomised, Multicentre, Open-label, Phase 3 study2022-03-23T00:00:00ZEpigenetic Modifications in Lymphoma and Their Role in the Classification of LymphomasPrince, Henry MilesYannakou, Costashttp://hdl.handle.net/11434/21252022-08-15T03:59:46Z2022-02-21T00:00:00ZTitle: Epigenetic Modifications in Lymphoma and Their Role in the Classification of Lymphomas
Epworth Authors: Prince, Henry Miles; Yannakou, Costas
Abstract: The characterisation of the lymphoma epigenome has provided insight into mechanisms involved in lymphomagenesis. Multiple lymphoma subtypes demonstrate recurrent mutations in key epigenetic regulators that have been utilised to define clinicogenetic groups that can predict clinical behaviour in these heterogenous entities. The high frequency of mutations in epigenetic regulators provides rationale to incorporate these in the classification of some subtypes of lymphoma. In addition, their recurrent nature provides a rationale to target such mutations, or the relevant pathway, for treatment. In this review, we summarised the available literature on epigenetic dysregulation in lymphoma and how it has been utilised in diagnosis and classification.2022-02-21T00:00:00ZManagement of hydroxyurea resistant or intolerant polycythemia vera.Raman, InduPrince, MilesYannakou, Costashttp://hdl.handle.net/11434/20552022-04-14T03:22:30Z2021-05-05T00:00:00ZTitle: Management of hydroxyurea resistant or intolerant polycythemia vera.
Epworth Authors: Raman, Indu; Prince, Miles; Yannakou, Costas
Abstract: Polycythemia vera is a Philadelphia negative myeloproliferative neoplasm characterized by erythrocytosis in which the major cause of morbidity and mortality is thrombosis. Aspirin and hematocrit reduction by venesection or cytoreductive therapy are at the cornerstone of management. First line cytoreductive therapy in high-risk patients is hydroxyurea; however, its use is associated with toxicities and resistance in a significant proportion of patients. In a disease with a long overall survival with appropriate treatment, it is imperative that other treatment options do not accelerate the risk of progression to acute leukemia. The following review will appraise the evidence of interferon, ruxolitinib, and other agents in management of hydroxyurea resistant or intolerant polycythemia vera.2021-05-05T00:00:00Z