Publications by authors named "Ian Irving"

13 Publications

  • Page 1 of 1

Pralatrexate in relapsed/refractory T-cell lymphoma: a retrospective multicenter study.

Leuk Lymphoma 2021 02 7;62(2):330-336. Epub 2020 Oct 7.

Division of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

We present a retrospective multicenter study of pralatrexate treatment outcomes in an Australian practice setting for patients with relapsed/refractory T-cell lymphoma who had failed 1+ systemic therapies, treated a compassionate access program. Endpoints assessed included response rates, toxicities, and subsequent therapies. Progression-free survival (PFS), time to next treatment (TTNT), event-free survival (EFS), overall survival (OS), and time to best response, were assessed by Kaplan-Meier analysis. The study included 31 patients, with median age 69 years. We demonstrated ORR of 35.5% ( = 11), including 4 complete responses (13%) and 7 partial responses (23%). The predicted median OS was 10 months, with EFS of 9 months, and PFS of 9 months. Median TTNT was 8 months. Mucositis was the most commonly observed toxicity. This study - the second largest real-world cohort reported to date - underscores the importance of pralatrexate in relapsed/refractory T-cell lymphoma, as well as its acceptable toxicity profile.
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http://dx.doi.org/10.1080/10428194.2020.1827241DOI Listing
February 2021

A consensus statement on the use of biosimilar medicines in hematology in Australia.

Asia Pac J Clin Oncol 2020 Aug 14;16(4):211-221. Epub 2020 Apr 14.

Monash Haematology, Monash Health, Clayton, Victoria, Australia.

Despite their availability for over a decade, the exact nature of biosimilar medicines is still poorly understood with paucity of clear treatment guidelines for their use in clinical practice in Australia. Although hematologists have had experience with biosimilars in the setting of supportive care, with the approval of the first biosimilar rituximab in hematological malignancies, it is important to revisit this topic. To inform the use of biosimilar medicines in clinical practice, we have developed a consensus statement from an Expert Panel of Australian hematologists, oncologists, and cancer pharmacists. These recommendations address the approach to use of biosimilar products in place of the corresponding reference medicine in a number of different clinical contexts. Our recommendations are based on the premise that biosimilar medicines can be considered therapeutically equivalent to their reference brand and used in a similar way to the reference product in any approved indication. We advocate for local approaches to the provision of patient information, dispensing of the intended brand and pharmacovigilance, to be developed in consultation with local hematologists and aim to improve confidence in the appropriate use of biosimilar medicines and their expected outcomes among hematologists.
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http://dx.doi.org/10.1111/ajco.13337DOI Listing
August 2020

A 14-year retrospective analysis of indications and outcomes of autologous haemopoietic stem cell transplantation in regional Queensland: a single-centre experience.

Intern Med J 2020 02;50(2):214-221

Icon Group, Brisbane, Queensland, Australia.

Background: The Townsville Hospital is a tertiary hospital in North Queensland with one of the largest regional transplant centres in Australia, performing primarily autologous haemopoietic stem cell transplants (HSCT) for various haematological malignancies.

Aims: This single-centre, retrospective, observational study aims to describe the activity and outcomes of autologous HSCT at The Townsville Hospital between 2003 and 2017 to verify safety standards.

Methods: Patient-level data were collected, including demographics, frequency and indication for transplant, conditioning, current clinical status and cause of death. Key outcomes included overall survival, non-relapse mortality, incidence of therapy-related neoplasm and causes of death. Progression-free survival in the multiple myeloma (MM) subgroup was also assessed.

Results: There were 319 autologous HSCT in 286 patients, with a median age of 58 years (range 14-71 years); 62% of patients were male. Indications for transplantation were: MM 53.7%, non-Hodgkin lymphoma 29.4%, Hodgkin lymphoma 5.0% and other 11.9%. Causes of death were: disease progression/relapse (65.2%), second malignancy (17.0%), infection (9.8%) and other (8.0%). Non-relapse mortality was 1.2% (95% confidence interval 0.4-3.0) and 3.2% (1.7-5.7) at 100 days and 1 year, respectively, post-HSCT. Overall survival at 2 years was 81.0% (73.8-86.4) for MM and 69.6% (58.8-78.1) for non-Hodgkin lymphoma. The median progression-free survival in the MM cohort was 3.3 years.

Conclusion: The Townsville Hospital transplant centre provides an important transplant service in regional Queensland, with outcomes comparable to national data. We reported a relatively high rate of second malignancy as a cause of death.
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http://dx.doi.org/10.1111/imj.14395DOI Listing
February 2020

The relationship between CD34+ stem cell dose and time to neutrophil recovery in autologous haematopoietic stem cell recipients-A single centre experience.

Transfus Apher Sci 2018 Aug 6;57(4):532-536. Epub 2018 Jun 6.

Icon Cancer Care, Brisbane, Australia.

A retrospective, observational study was performed of 112 patients who underwent autologous haematopoietic stem cell transplantation (ASCT) to determine the relationship between CD34+ stem cell dose and neutrophil engraftment. Importantly, a novel approach to more accurately calculate time to neutrophil engraftment was employed. The results demonstrated that a higher CD34+ stem cell dose was associated with faster neutrophil recovery (P < 0.05). CD34+ stem cell dose using actual and ideal patient body weight were both equally predictive of neutrophil engraftment as were absolute and viable CD34+ measurements. The clinical implications for this relationship are limited with an increase in CD34+ stem cell dose by 1 × 10/kg reducing the neutrophil engraftment time by only 3 h and 50 min. The median time to neutrophil recovery was 217 h (9 days and 1 h) and this relatively early engraftment time may be related to an early initiation of granulocyte colony-stimulating factor (G-CSF) on day +1 post-transplant. Female patients engrafted 17 h faster than their male counterparts on multi-variate analysis (P < 0.05). Conditioning chemotherapy, bacteraemia, G-CSF dose/kg body weight and increasing age had no impact on time to neutrophil recovery.
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http://dx.doi.org/10.1016/j.transci.2018.05.031DOI Listing
August 2018

Efficacy and safety of nilotinib 300 mg twice daily in patients with chronic myeloid leukemia in chronic phase who are intolerant to prior tyrosine kinase inhibitors: Results from the Phase IIIb ENESTswift study.

Leuk Res 2018 04 21;67:109-115. Epub 2018 Feb 21.

Haematology Division, Royal Adelaide Hospital, University of Adelaide and South Australian Health and Medical Research Institute, Adelaide, Australia. Electronic address:

Background: Some patients receiving a tyrosine kinase inhibitor (TKI) for the first-line treatment of chronic phase chronic myeloid leukemia (CML-CP) experience intolerable adverse events. Management strategies include dose adjustments, interrupting or discontinuing therapy, or switching to an alternative TKI.

Methods: This multicenter, single-arm, Phase IIIb study included CML-CP patients intolerant of, but responsive to, first-line treatment with imatinib or dasatinib. All patients were switched to nilotinib 300 mg bid for up to 24 months. The primary endpoint was achievement of MR4.5 (BCR-ABL transcript level of ≤0.0032% on the International Scale) by 24 months.

Results: Twenty patients were enrolled in the study (16 imatinib-intolerant, 4 dasatinib-intolerant); which was halted early because of low recruitment. After the switch to nilotinib 300 mg bid, MR4.5 at any time point up to month 24 was achieved in 10 of 20 patients (50%) in the full analysis set. Of the non-hematological adverse events associated with intolerance to prior imatinib or dasatinib, 74% resolved within 12 weeks of switching to nilotinib 300 mg bid.

Conclusion: Nilotinib 300 mg bid shows minimal cross intolerance in patients with CML-CP who have prior toxicities to other TKIs and can lead to deep molecular responses.
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http://dx.doi.org/10.1016/j.leukres.2018.02.013DOI Listing
April 2018

FLT3-ITD positive acute myeloid leukemia: A retrospective analysis of the role of allogeneic transplant and allelic ratio in patient management.

Asia Pac J Clin Oncol 2018 Dec 31;14(6):426-430. Epub 2018 Jan 31.

Cancer Care Services, Royal Brisbane and women's Hospital, Brisbane, Australia.

Aim: FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) positive AML is associated with increased relapse risk and reduced overall survival (OS) compared to non-FLT3-mutated AML. The aim of this study was to evaluate the impact of allelic ratio and allogeneic transplant on outcomes in FLT3-ITD+ AML.

Methods: A retrospective study across five centers in Queensland, Australia, was conducted to examine survival outcomes and impact of FLT3-ITD allelic ratio and allograft.

Results: Seventy-one patients were included in the study. OS was significantly better for patients who were able to be allografted in first complete remission (CR1; 50.1 months vs 8.5 months; P = 0.0002). We did not find allelic ratio to be predictive of outcome.

Conclusion: Transplantation in first complete remission is associated with improved outcomes for patients with FLT3+ AML. When feasible transplantation in CR1 is recommended. We do not currently recommend using allelic ratio to stratify risk unless this has been validated by local results.
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http://dx.doi.org/10.1111/ajco.12827DOI Listing
December 2018

Effects of intensive induction and consolidation chemotherapy with idarubicin and high dose cytarabine on minimal residual disease levels in newly diagnosed adult precursor-B acute lymphoblastic leukemia.

Contemp Clin Trials Commun 2016 Dec 22;4:9-13. Epub 2016 Jun 22.

Department of Haematology, Peter MacCallum Cancer Centre, University of Melbourne, Victoria, Australia.

An intensive induction regimen, consisting of idarubicin and high dose cytarabine, was assessed in 19 adult patients, median age 44 years, with newly diagnosed precursor-B acute lymphoblastic leukemia (ALL). Patients achieving a complete response (CR) were given an attenuated consolidation course. The primary endpoints were induction death rate and incidence of serious non-hematological toxicity. Grades 3-4 diarrhoea occurred in 47% of patients during induction. Two patients (11%) died during induction therapy, and 2 were withdrawn due to resistant disease or prolonged marrow hypoplasia. Fifteen patients achieved CR (79%), but levels of minimal residual disease (MRD) after induction were comparable with those previously observed using a modified pediatric protocol. Overall survival at 5 years was 36.8% while leukemia-free survival was 44.1%. An intensive AML protocol used in adults with ALL resulted in substantial toxicity and provided similar levels of cytoreduction to conventional ALL protocols, without improving long-term outcomes.
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http://dx.doi.org/10.1016/j.conctc.2016.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935861PMC
December 2016

An imatinib-only window followed by imatinib and chemotherapy for Philadelphia chromosome-positive acute leukemia: long-term results of the CMLALL1 trial.

Leuk Lymphoma 2015 Mar 4;56(3):630-8. Epub 2014 Aug 4.

Cancer Therapeutics Unit, Nucleus Network , Melbourne, Victoria , Australia.

We report long-term results in 40 patients with Philadlephia chromosome-positive (Ph+) acute leukemia who received an imatinib monotherapy window to evaluate in vivo effects on BCR-ABL signaling prior to induction chemotherapy. The first 25 patients (cohort 1) received the LALA-94 protocol without further imatinib (newly diagnosed Ph+ acute lymphoblastic leukemia [ALL]) or induction chemotherapy followed by single-agent imatinib. Subsequent patients (cohort 2) continued imatinib concurrently with either LALA-94 (newly diagnosed Ph + ALL) or other intensive chemotherapy regimens. Cohort 2 had a complete response (CR) rate of 93% and 5-year survival of 69%. For newly diagnosed Ph+ ALL, survival was superior in cohort 2 compared with cohort 1. Toxicity was similar to that expected for chemotherapy alone. Among 10 evaluable patients, rapid loss of phospho-CRKL occurred during the imatinib window in seven patients (all achieved CR) and incomplete inhibition in three patients (none with CR). In summary, a pharmacodynamic window design permitted biomarker assessment of BCR-ABL targeting without compromising clinical outcomes.
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http://dx.doi.org/10.3109/10428194.2014.925547DOI Listing
March 2015

Excellent outcomes for adolescents and adults with acute lymphoblastic leukemia and lymphoma without allogeneic stem cell transplant: the FRALLE-93 pediatric protocol.

Leuk Lymphoma 2014 Dec 19;55(12):2801-7. Epub 2014 Mar 19.

Box Hill Hospital , Box Hill , Australia.

Adolescents and adults with acute lymphoblastic leukemia/lymphoma (ALL) have better outcomes when treated using pediatric protocols compared with treatment using adult protocols. We reviewed the progress and outcomes of 40 adolescents and adults up to 45 years of age, from three Australian centers, treated on the intensive French group for childhood ALL (FRALLE)-93 pediatric protocol. All except one patient achieved a morphologic complete remission following induction chemotherapy. Three-year overall survival for all-risk and standard-risk disease was 70% and 75%, respectively. The treatment protocol was generally well tolerated with no treatment related mortality. The FRALLE-93 pediatric protocol showed excellent overall survival for patients with standard-risk disease, without the need for allogeneic hematopoietic stem cell transplant in first remission.
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http://dx.doi.org/10.3109/10428194.2014.894191DOI Listing
December 2014

Chronic myeloid leukemia in the Asia-Pacific region: current practice, challenges and opportunities in the targeted therapy era.

Leuk Res 2010 Nov;34(11):1459-71

Division of Hematology, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.

Chronic myeloid leukemia (CML) management varies across Asia due to disparities in affluence and healthcare provision. We surveyed CML management practice at 33 hospitals in 14 countries/regions to identify treatment challenges and opportunities for harmonization. Patients were generally treated according to international guidelines; however, tyrosine kinase inhibitors (TKIs) and molecular monitoring are inaccessible to many patients not covered by national insurance or eligible for subsidized treatment. Late diagnosis and suboptimal monitoring, often due to cost and accessibility issues, are challenges. Priorities for Asia include: extending accessibility to TKIs; specialist laboratory monitoring; and enriching data to support regional CML management guidelines.
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http://dx.doi.org/10.1016/j.leukres.2010.03.033DOI Listing
November 2010

Hemoglobin Titusville, a low oxygen affinity variant hemoglobin, in a family of Northern European background.

Am J Hematol 2004 Dec;77(4):384-6

Hemoglobin Diagnostic Reference Laboratory, Boston Medical Center, Boston, Massachusetts 02118, USA.

We report the second case of Hb Titusville in a family of Northern European background. This variant hemoglobin caused by an alpha-globin gene mutation has decreased oxygen affinity. Correct diagnosis is clinically important to spare affected individuals extensive investigations into other causes of low oxygen saturation in peripheral blood.
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http://dx.doi.org/10.1002/ajh.20209DOI Listing
December 2004