ORCID Profile
0000-0002-9210-5373
Current Organisations
Peter MacCallum Cancer Centre and Royal Melbourne Hospital
,
Royal College of Physicians
,
University of Melbourne
,
University of Pune
,
Royal Australasian College of Physicians
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Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22537006
Abstract: Exposure-response relationship between CX-5461 levels and rDNA transcription rate in normal PBMCs
Publisher: Informa UK Limited
Date: 07-10-2010
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22537003
Abstract: All Supplementary Methods and associated references
Publisher: Informa UK Limited
Date: 22-01-2019
Publisher: Informa UK Limited
Date: 02-12-2021
DOI: 10.1080/17474086.2021.2022471
Abstract: Multiple Myeloma (MM) accounts for 1-2% of all malignancies but is the second most common hematological malignancy. It is characterized by a proliferation of malignant plasma cells. The treatment paradigm of MM in Australia is traditionally hospital-based, complex, and costly. While MM comprises 1-2% of cancer diagnoses, it appears in the top 10 cancer diagnoses requiring hospital admission. The cumulative time spent receiving treatment is a significant burden for patients. The ability to receive treatment at home and maximize time away from hospital-based settings is a key preference for patients receiving anticancer therapies over a prolonged period of time. The Peter MacCallum Cancer Centre and Royal Melbourne Hospital's combined Clinical Hematology Unit has collaborated with their Hospital in the Home departments to develop several innovative programs to address this. We describe our current active programs and potential developments in home-based MM therapy. We have enabled large numbers of patients to receive complex therapies in their own home and the COVID-19 pandemic has increased the pace of the roll out without any compromise in safety. We anticipate that the next raft of immunotherapies will be able to transition into the @Home treatment setting in the coming years.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22537000
Abstract: All Supplementary Tables
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.JBIOMECH.2013.05.011
Abstract: The objective of this study was to examine mechanisms underpinning the reduction in knee adduction moment (KAM) and changes in frontal plane knee-ground reaction force (GRF) lever arm with a modified shoe that incorporates both a variable-stiffness sole and lateral wedging. Thirty in iduals with symptomatic knee osteoarthritis (OA) and 30 overweight asymptomatic in iduals underwent gait analyses wearing modified and standard shoes. In both groups, there was a decrease in the lever arm (p<0.001), and a lateral shift in the center of pressure (COP) offset (p ≤ 0.001). There was no change in frontal plane or medial-lateral GRF magnitudes, lateral trunk lean or stance duration in either group. There was no significant change in the frontal plane hip-knee-ankle angle in the OA group but a significant decrease in the overweight group (p=0.003). In both groups, changes in lever arm and frontal plane GRF magnitude predicted change in peak KAM (p<0.01), but only change in lever arm predicted change in KAM impulse (p<0.001). In the OA group, changes in COP offset and medial-lateral GRF magnitude predicted change in lever arm (p<0.05), whereas changes in trunk lean and hip-knee-ankle angle predicted change in lever arm in the overweight group (p=0.01). In conclusion, the change in lever arm contributed the most to explaining change in KAM parameters with modified shoes. The change in the lever arm was driven by changes evident at the foot in the OA participants (COP and medial-lateral GRF), and by more proximal changes (hip-knee-ankle angle and trunk lean) in the overweight group.
Publisher: Informa UK Limited
Date: 24-08-2023
Publisher: American Society of Hematology
Date: 05-01-2012
Publisher: Future Medicine Ltd
Date: 12-2013
DOI: 10.2217/FON.13.220
Abstract: Cutaneous T-cell lymphomas are relatively rare lymphomas and the most common form is mycosis fungoides. Its rare leukemic variant is Sezary syndrome. Advanced-stage disease is typically treated with bexarotene (a retinoid), IFN-α or conventional chemotherapeutic agents, but relapses are inevitable. Histone deacetylase inhibitors that modify the epigenome are an attractive addition to the armamentarium. Based on two large Phase II studies, the US FDA approved intravenous romidepsin for patients with relapsed/refractory cutaneous T-cell lymphomas. Romidepsin provides a subset of patients with an opportunity for prolonged clinical responses with a tolerable side-effect profile.
Publisher: MDPI AG
Date: 26-10-2020
Abstract: Peripheral T-cell lymphomas (PTCLs) are distinct pathological entities with clinical advancements lagging behind their B-cell lymphoma counterpart. Frequently aggressive in their clinical behaviour, clinicians are constantly challenged with low complete remission rates, early relapses and failure to achieve long-term responses despite aggressive first-line chemotherapy, resulting in poor overall survival in the majority of patients. There is currently no consensus regarding the optimal therapy for PTCL and treatment approaches are mainly derived from prospective phase II studies, registry data and retrospective studies. Despite its biological heterogeneity, a less than satisfactory “one-size-fits-all” approach has been adopted to date. Although its role remains controversial, for many years, haematopoietic stem cell transplantation has been adopted by clinicians with the aim of overcoming poor outcomes by consolidating responses. In this review, we aim to define the role of both autologous and allogeneic stem cell transplantation in PTCL in both frontline and salvage settings, especially in the context of recent advancements in this field.
Publisher: Informa UK Limited
Date: 09-09-2013
Publisher: Springer Science and Business Media LLC
Date: 05-10-2021
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 13-08-2021
Publisher: Informa UK Limited
Date: 25-10-2022
Publisher: Informa UK Limited
Date: 09-08-2017
Publisher: Springer Science and Business Media LLC
Date: 26-08-2022
Publisher: Research Square Platform LLC
Date: 16-08-2022
DOI: 10.21203/RS.3.RS-1952346/V1
Abstract: Purpose Health care professionals (HCP) play a vital role in effectiveness of prehabilitation programs, but information is limited about what assists HCP deliver an effective service. This study evaluated HCP perceptions of enablers and barriers to two behaviours: referral for, and delivery of, multidisciplinary prehabilitation prior to autologous stem cell transplant. Methods Based on the Theoretical Domains Framework (TDF) of behaviour change, we conducted semi-structured interviews, purposively s ling 14 participants (from various healthcare disciplines) at a tertiary cancer centre. Discipline-specific topic guides were created based on the TDF and the behaviours appropriate to each discipline. Interviews were audio-recorded, transcribed verbatim, anonymised, content analysed (grouping, then labelling, thematically similar responses) and classified into theoretical domains. Structured decision rules were used to classify themes as high, medium or low priority. Results Fifty enablers and 31 barriers were identified of these 26 enablers and 16 barriers classified as high priority. Four domains had the most frequent high-priority enablers: Social professional role and identity (e.g., multidisciplinary teamwork) Beliefs about consequences (e.g., patient benefit) Memory, attention and decision processes (e.g., refer as early as possible) and Environmental context and resources (e.g., electronic medical records are beneficial). High-priority barriers were most frequent in four domains: Memory, attention and decision processes (e.g., conflicting views about who should be referred) Environmental context and resources (e.g., lack of time) Social influences (e.g., families) and Emotions (e.g., patient distress). Conclusion Participants reported more enablers than barriers. Findings can support delivery of prehabilitation programs in hospital settings where uptake remains low.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22537003.V1
Abstract: All Supplementary Methods and associated references
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22537015
Abstract: Significant dermatological toxicities associated with CX-5461 treatment
Publisher: Elsevier BV
Date: 02-2023
Publisher: S. Karger AG
Date: 2012
DOI: 10.1159/000343661
Abstract: b i Background: /i /b The Stanford BCNU protocol (carmustine, etoposide and cyclophosphamide) is a high-dose conditioning regimen widely used prior to autologous stem cell transplantation. While acute renal failure requiring renal replacement therapy is a known but rare complication of autologous stem cell transplantation, acute nephrotoxicity following carmustine and etoposide has not yet been reported. b i Case: /i /b We present the first case of carmustine-induced acute kidney injury in the setting of autologous stem cell transplantation and perform a review of the literature. Renal failure was associated with a sharp rise in serum creatinine, oliguria and trace proteinuria. Urgent haemodialysis was required however, renal failure resolved after 7 days. b i Con /i /b b i clusion: /i /b Although a rare complication, its severity mandates close monitoring of renal function as early recognition and treatment may limit long-term sequelae.
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 19-05-2016
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22537012
Abstract: Pharmacokinetics analysis of CX-5461 in patients with advanced hematological disease
Publisher: American Society of Hematology
Date: 24-11-2011
DOI: 10.1182/BLOOD-2011-08-372854
Abstract: Intravenous alemtuzumab is an effective and well-tolerated treatment for T-cell prolymphocytic leukemia (T-PLL). Alemtuzumab given intravenously as first-line treatment in 32 patients resulted in an overall response rate of 91% with 81% complete responses. Studies in B-cell chronic lymphocytic leukemia have shown subcutaneous alemtuzumab to be equally as effective as intravenous alemtuzumab. The UKCLL05 pilot study examined the efficacy and toxicity of this more convenient method of administration in 9 previously untreated patients with T-PLL. Only 3 of 9 patients (33%) responded to treatment. Furthermore, 2 of 9 patients (22%) died while on treatment. Recruitment was terminated because of these poor results. After rescue therapy with intravenous alemtuzumab and/or pentostatin, median progression-free survival and overall survival were similar to the intravenous group. Alemtuzumab delivered intravenously, but not subcutaneously, remains the treatment of choice for previously untreated T-PLL. This study is registered at www.eudract.ema.europa.eu as #2004-004636-31.
Publisher: Springer Science and Business Media LLC
Date: 20-07-2021
Publisher: Impact Journals, LLC
Date: 06-07-2016
Publisher: Wiley
Date: 18-07-2022
DOI: 10.1111/IMJ.15496
Abstract: High‐intensity chemotherapy and advances in novel immunotherapies have seen the emergence of cytomegalovirus (CMV) infections in cancer patients other than allogeneic haemopoietic cell transplantation (HCT). Aim To evaluate the epidemiology, clinical characteristics and outcomes of CMV infection in this population. A retrospective review of cancer patients other than allogeneic HCT who had CMV DNAemia and/or disease from July 2013 till May 2020 at a quaternary cancer centre was performed. Of 11 485 cancer patients who underwent treatment during this period, 953 patients had CMV DNA testing performed and 238 of them had CMV DNAemia. After excluding patients with allogeneic HCT, 62 patients with CMV DNAemia were identified, of whom 10 had concurrent CMV disease. The most frequent underlying malignancies were B‐cell lymphoproliferative disease (LPD) (31% 19/62), T‐cell LPD (21% 13/62), chronic lymphocytic leukaemia (11% 7/62) and multiple myeloma (10% 6/62). Most patients had lymphopenia (77% 48/62), multiple cancer therapies (63% 39/62 received ≥2 previous therapies), co‐infection (56% 35/62 had ≥1 co‐infection) and corticosteroid therapy (48% 30/62) within 1 month before CMV diagnosis. CMV DNAemia and disease were observed in patients receiving novel immunotherapies, including bispecific antibody therapy, chimeric‐antigen receptor T‐cell therapy and immune checkpoint inhibitors. Patients with haematological malignancy, particularly B‐cell LPD, T‐cell LPD, chronic lymphocytic leukaemia and multiple myeloma, were frequently identified to have CMV DNAemia and disease. Lymphopenia, multiple cancer therapies, co‐infection and recent receipt of systemic corticosteroids were also commonly observed. Future studies are necessary to determine optimal identification and management of CMV in these patients.
Publisher: Springer Science and Business Media LLC
Date: 20-08-2015
DOI: 10.1038/LEU.2014.247
Abstract: The BTK (Bruton's tyrosine kinase) inhibitor ibrutinib is associated with an increased risk of bleeding. A previous study reported defects in collagen- and adenosine diphosphate (ADP)-dependent platelet responses when ibrutinib was added ex vivo to patient s les. Whereas the collagen defect is expected given the central role of BTK in glycoprotein VI signaling, the ADP defect lacks a mechanistic explanation. In order to determine the real-life consequences of BTK platelet blockade, we performed light transmission aggregometry in 23 patients receiving ibrutinib treatment. All patients had reductions in collagen-mediated platelet aggregation, with a significant association between the degree of inhibition and the occurrence of clinical bleeding or bruising (P=0.044). This collagen defect was reversible on drug cessation. In contrast to the previous ex vivo report, we found no in vivo ADP defects in subjects receiving standard doses of ibrutinib. These results establish platelet light transmission aggregometry as a method for gauging, at least qualitatively, the severity of platelet impairment in patients receiving ibrutinib treatment.
Publisher: Wiley
Date: 23-06-2013
DOI: 10.1111/TID.12106
Abstract: Cytomegalovirus (CMV) retinitis is an uncommon manifestation of CMV disease and is a marker of severe and profound immunosuppression in human immunodeficiency virus-positive patients. Here, we describe 2 cases of CMV retinitis in myeloma patients with progressive disease, following autologous stem cell transplantation and immunomodulatory therapy for myeloma. To our knowledge, this is the first report of CMV retinitis in this patient population. This report illustrates the need for close monitoring of relapsed and refractory myeloma patients for new presentations of opportunistic infections secondary to severe immunosuppression.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.C.6548299.V1
Abstract: Abstract RNA polymerase I (Pol I) transcription of ribosomal RNA genes (rDNA) is tightly regulated downstream of oncogenic pathways, and its dysregulation is a common feature in cancer. We evaluated CX-5461, the first-in-class selective rDNA transcription inhibitor, in a first-in-human, phase I dose-escalation study in advanced hematologic cancers. Administration of CX-5461 intravenously once every 3 weeks to 5 cohorts determined an MTD of 170 mg/m sup /sup , with a predictable pharmacokinetic profile. The dose-limiting toxicity was palmar–plantar erythrodysesthesia photosensitivity was a dose-independent adverse event (AE), manageable by preventive measures. CX-5461 induced rapid on-target inhibition of rDNA transcription, with p53 activation detected in tumor cells from one patient achieving a clinical response. One patient with anaplastic large cell lymphoma attained a prolonged partial response and 5 patients with myeloma and diffuse large B-cell lymphoma achieved stable disease as best response. CX-5461 is safe at doses associated with clinical benefit and dermatologic AEs are manageable. Significance: CX-5461 is a first-in-class selective inhibitor of rDNA transcription. This first-in-human study establishes the feasibility of targeting this process, demonstrating single-agent antitumor activity against advanced hematologic cancers with predictable pharmacokinetics and a safety profile allowing prolonged dosing. Consistent with preclinical data, antitumor activity was observed in i TP53 /i wild-type and mutant malignancies. i This article is highlighted in the In This Issue feature, p. 983 /i /
Publisher: Wiley
Date: 26-12-2020
DOI: 10.1111/AJD.13467
Abstract: Primary cutaneous lymphomas represent a heterogeneous group of T‐ and B‐cell lymphomas with distinct clinical presentations, histopathologic features, treatment approaches and outcomes. The cutaneous T‐cell lymphomas, which include mycosis fungoides and Sézary syndrome, account for the majority of the cutaneous lymphomas. This Clinical Practice Statement is reflective of the current clinical practice in Australia. An expanded form of the Clinical Practice Statement (and updates), along with helpful patient resources and access to support groups, can be found at the following ( www.australasianlymphomaalliance.org.au ).
Publisher: Informa UK Limited
Date: 08-2013
DOI: 10.1586/17474086.2013.814833
Abstract: Peripheral T-cell lymphoma (PTCL) is comprised of a rare heterogeneous group of diseases with erse clinical presentations however outcomes associated with conventional chemotherapy are generally poor in the majority of patients. Newer approaches, which include dose-intensification and agents with novel mechanisms of action, are needed to improve outcomes in this group of patients. In this review we examine the results of two recent large Phase II trials with romidepsin, a histone deacetylase inhibitor which shows considerable activity and good tolerability in patients with T-cell lymphoma. These initial results observed with single-agent romidepsin provide a foundation for exploring combination strategies and demonstrates proof-of-principle that other such drugs with similar mechanisms of action may be effective in T-cell lymphoma.
Publisher: Elsevier BV
Date: 06-2021
DOI: 10.1016/J.CLML.2021.01.012
Abstract: Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphomas that are frequently associated with a poor prognosis. For many decades, the standard-of-care has been CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone)-based therapy, but it is well-recognized that survival outcomes are unsatisfactory, especially when compared with B-cell lymphomas. Major recent advances in cancer diagnosis and management have the potential to significantly improve PTCL outcomes. These include: (1) improved diagnostic techniques that incorporate molecular genetic data to further refine diagnosis and subtyping (2) the development of novel agents and (3) improved monitoring modalities, such as
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22537000.V1
Abstract: All Supplementary Tables
Publisher: Springer Science and Business Media LLC
Date: 24-10-2005
Publisher: American Association for Cancer Research (AACR)
Date: 31-05-0770
DOI: 10.1158/2159-8290.22537006.V1
Abstract: Exposure-response relationship between CX-5461 levels and rDNA transcription rate in normal PBMCs
Publisher: American Society of Hematology
Date: 26-10-2023
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.CLML.2012.09.017
Abstract: The routine use of recombinant human granulocyte-colony stimulating factor (rhG-CSF) after high-dose chemotherapy and autologous stem cell transplantation (auto-SCT) is associated with increased costs. We prospectively explored a strategy that used prophylactic delayed filgrastim only in patients with risk factors. This sequential cohort analysis compared the outcomes of consecutive patients, treated on the risk-adapted protocol (RAP) (risk factors: prior febrile neutropenia age >60 years and CD34+ cell infused dose of <2 × 10(6/)/kg), who received filgrastim from day +6 after auto-SCT with a historical cohort (historical day-1 cohort [HD1]), who received filgrastim from day +1. Eighty-two patients were treated in the RAP cohort and compared with 115 patients in the HD1 cohort. There were no differences in median age (55 years) or median CD34+ cell dose (5.21 × 10(6)/kg [range, 2-62.2 × 10(6)/kg] vs. 5.24 × 10(6)/kg [range, 2.4-29.8 × 10(6)/kg]). Filgrastim was used for 6 fewer days in the RAP cohort (median 5 days [range, 0-11 days] vs. 11 days [range, 9-47 days]). There was a small absolute but significant difference in median time to neutrophil recovery in the HD1 cohort for the whole group, 10 days (range, 8-46 days) vs. 11 days (range, 9-22 days) (P = .03) and in patients with myeloma 10 days (range, 9-14 days) vs. 11 days (range, 9-18 days) (P < .0001) as compared to the RAP cohort. There was no difference in median inpatient duration, 13 days (range, 10-26 days) vs. 12 days (range, 1-38 days) (P = .22) and 3-year survival (79% vs. 83% [P = .43]) between HD1 and RAP cohorts respectively. The use of a RAP to identify patients likely to benefit from prophylactic filgrastim is safe and results in cost savings. Patients with myeloma benefit from earlier introduction of filgrastim in terms of neutrophil recovery this disease-specific observation is an important consideration for future studies.
Publisher: Wiley
Date: 28-12-2021
DOI: 10.1111/TID.13547
Abstract: In iduals diagnosed with acute lymphoid and myeloid malignancies are at significant risk of invasive fungal and bacterial infections secondary to their marked immunocompromised states with a significant high risk of mortality. The role of metabolic imaging with 18F‐Fluorodeoxyglucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) has been increasingly recognized in optimizing the diagnosis of invasive infection, monitoring the response to therapy and guiding the duration of antimicrobial therapy or need to escalate to surgical intervention. Two distinct cases of pulmonary co‐infection of rare fungal and bacterial pathogens are explored in severely immunocompromised in iduals where FDG PET/CT aided both patients to make a full recovery and transition to HCT. The first case explores mixed Scedosporium apiospermum and Rhizomucor pulmonary infection on a background of T cell/myeloid mixed phenotype acute leukemia ultimately warranting long‐term antifungal therapy and lobectomy prior to HCT. The second case explores Fusarium and Nocardia pulmonary infection on a background of relapsed AML also warranting surgical resection with lobectomy and long‐term antimicrobials prior to transition to HCT. The cases highlight the utility of FDG PET/CT to support the diagnosis of infections, including the presence or absence of disseminated infection, and to provide highly sensitive monitoring of the infection over time. FDG PET/CT played a key role in directing therapy duration decisions and prompted the necessity for surgical intervention. Ultimately, the use of FDG PET/CT allowed for a successful transition to HCT highlighting its value in this clinical setting. FDG PET/CT has an emerging role in the diagnostic and monitoring pathway for complex infections in high‐risk immunocompromised patients.
Publisher: Informa UK Limited
Date: 03-2009
Abstract: T-cell prolymphocytic leukemia is a rare post-thymic lymphoid disorder, which has distinctive clinical, morphologic, immunophenotypic and cytogenetic features. It has previously been associated with an aggressive course, poor response to conventional chemotherapy and a short median survival. Treatment with purine analogs and the monoclonal antibody alemtuzumab has resulted in significantly higher response rates and increased survival. However, responses are transient and allogeneic hematopoietic progenitor-cell transplantation remains the only potential curative option. The proportion of patients eligible for transplant is low, owing to the older age group of patients, and nonmyeloablative transplantation is a promising alternative that needs to be explored.
Publisher: Informa Healthcare
Date: 03-07-2013
DOI: 10.1517/13543784.2013.815165
Abstract: Histone deacetylase inhibitors (HDACIs) are a class of antineoplastic agent targeting the epigenome, specifically chromatin remodelling, resulting in modulation of genes responsible for apoptosis and cell cycle regulation, and also hyperacetylation of many non-histone proteins. Panobinostat is a potent pan-histone inhibitor of HDAC enzymes implicated in cancer development and progression. Activity has been demonstrated in hematological diseases, such as cutaneous T-cell lymphoma (CTCL), Hodgkin lymphoma (HL), myeloma and myeloid malignancies. We discuss basic pharmacology, followed by early phase trial results and analyse recent large Phase II trials in HL, CTCL, myeloid malignancies and Waldenstrom's macroglobulinemia (WM). Future directions for drug development including potential predictive biomarkers are considered. The results of Phase II trials prove that oral panobinostat is deliverable with dosing regimens of three times per week, either weekly or biweekly. The major hematologic side-effect of myelosuppression, in particular thrombocytopenia, is transient and manageable, as are the non-hematologic side-effects. Encouraging responses are observed in HL, CTCL, myelofibrosis and WM. The safety and efficacy results from studies of combination therapy with azacitidine in acute myeloid leukemia and myelodysplastic syndromes suggest that this agent may find a place in the management of a range of hematologic cancers.
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22537012.V1
Abstract: Pharmacokinetics analysis of CX-5461 in patients with advanced hematological disease
Publisher: American Society of Hematology
Date: 2015
DOI: 10.1182/BLOOD-2014-07-588236
Abstract: Chemotherapy results in a short median time to next treatment in patients with mycosis fungoides/Sézary syndrome. α-interferon achieves a superior time to next treatment compared with chemotherapy, regardless of stage.
Publisher: American Society of Hematology
Date: 16-03-2023
Publisher: American Association for Cancer Research (AACR)
Date: 07-2019
DOI: 10.1158/1078-0432.CCR-18-3470
Abstract: IL6 is important for the growth and survival of myeloma cells. This study evaluated blocking IL6 with siltuximab to delay the transition from high-risk smoldering multiple myeloma (SMM) to multiple myeloma. In a randomized, double-blind, placebo-controlled, multicenter study, 85 patients with high-risk SMM were randomized to 15 mg/kg siltuximab (43 patients) or placebo (42 patients). The primary endpoint was 1-year progression-free survival (PFS) rate, based on IMWG CRAB criteria. Secondary endpoints included progressive disease indicator rate, PFS, and safety. Median age was 62 years (range: 21–84) 57% were male and 87% had a baseline Eastern Cooperative Oncology Group score of 0. The 1-year PFS rate was 84.5% (siltuximab) and 74.4% (placebo). After a median follow-up of 29.2 months, 32.6% of PFS events occurred with siltuximab and 42.9% with placebo. Median PFS was not reached with siltuximab but was 23.5 months with placebo [HR 0.50 (95% confidence interval, 0.24–1.04) P = 0.0597]. The safety profile of siltuximab was comparable with placebo. Most adverse events in the siltuximab group were grade 2/3 the most common serious adverse events were infections/infestations, and renal/urinary disorders. Mortality was low in both groups (3 deaths in the siltuximab group and 4 in the placebo group). Although this study did not meet the prespecified protocol hypothesis criteria, data suggest that siltuximab may delay the progression of high-risk SMM.
Publisher: Elsevier BV
Date: 09-2018
Publisher: Informa UK Limited
Date: 07-09-2022
Publisher: American Association for Cancer Research (AACR)
Date: 08-2019
DOI: 10.1158/2159-8290.CD-18-1455
Abstract: CX-5461 is a first-in-class selective inhibitor of rDNA transcription. This first-in-human study establishes the feasibility of targeting this process, demonstrating single-agent antitumor activity against advanced hematologic cancers with predictable pharmacokinetics and a safety profile allowing prolonged dosing. Consistent with preclinical data, antitumor activity was observed in TP53 wild-type and mutant malignancies. This article is highlighted in the In This Issue feature, p. 983
Publisher: American Association for Cancer Research (AACR)
Date: 03-04-2023
DOI: 10.1158/2159-8290.22537015.V1
Abstract: Significant dermatological toxicities associated with CX-5461 treatment
Publisher: Informa UK Limited
Date: 29-01-2021
Publisher: Elsevier BV
Date: 11-2013
DOI: 10.1038/MT.2013.154
Publisher: Elsevier BV
Date: 08-2022
Publisher: Informa UK Limited
Date: 25-08-2016
Publisher: Informa UK Limited
Date: 02-08-2023
Publisher: Wiley
Date: 26-10-2017
DOI: 10.1111/BJH.14987
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Amit Khot.