Marliese Alexander

Ipilimumab in pretreated patients with unresectable or metastatic cutaneous, uveal and mucosal melanoma.

Objectives: To evaluate the efficacy and tolerability of ipilimumab in an Australian clinical setting, and to assess the association of response with melanoma subtype, BRAF mutation status, absolute lymphocyte count and incidence of serious immune‐related adverse events (AEs).

Australian consensus guidelines for the safe handling of monoclonal antibodies for cancer treatment by healthcare personnel

These consensus guidelines provide recommendations for the safe handling of monoclonal antibodies. Definitive recommendations are given for the minimum safe handling requirements to protect healthcare personnel. The seven recommendations cover: (i) appropriate determinants for evaluating occupational exposure risk; (ii) occupational risk level compared with other hazardous and non‐hazardous drugs; (iii) stratification of risk based on healthcare personnel factors; (iv) waste products; (v) interventions and safeguards; (vi) operational and clinical factors and (vii) handling recommendations. The seventh recommendation includes a risk assessment model and flow chart for institutions to consider and evaluate clinical and operational factors unique to individual healthcare services. These guidelines specifically evaluated monoclonal antibodies used in the Australian cancer clinical practice setting; however, the principles may be applicable to monoclonal antibodies used in non‐cancer settings. The guidelines are only applicable to parenterally administered agents.

A review of the evidence for occupational exposure risks to novel anticancer agents - A focus on monoclonal antibodies.

Introduction Evidence of occupational exposure risks to novel anticancer agents is limited and yet to be formally evaluated from the Australian healthcare perspective. Methods From March to September 2013 medical databases, organizational policies, drug monographs, and the World Wide Web were searched for evidence relating to occupational exposure to monoclonal antibodies, fusion proteins, gene therapies, and other unclassified novel anticancer agents. Results Australian legislation, national and international guidelines, and drug company information excluded novel agents or provided inconsistent risk assessments and safe handling recommendations. Monoclonal antibody guidelines reported conflicting information and were often divergent with available evidence and pharmacologic rationale demonstrating minimal internalisation ability and occupational exposure risk. Despite similar physiochemical, pharmacologic, and internalisation properties to monoclonal antibodies, fusion proteins were included in only a minority of guidelines. Clinical directives for the safe handling of gene therapies and live vaccines were limited, where available focusing on prevention against exposure and cross-contamination. Although mechanistically different, novel small molecule agents (proteasome inhibitors), possess similar physiochemical and internalisation properties to traditional cytotoxic agents warranting cytotoxic classification and handling. Conclusion Novel agents are rapidly emerging into clinical practice, and healthcare personnel have few resources to evaluate risk and provide safety recommendations. Novel agents possess differing physical, molecular and pharmacological profiles compared to traditional cytotoxic anticancer agents. Evaluation of occupational exposure risk should consider both toxicity and internalisation. Evidence-based guidance able to direct safe handling practices for novel anticancer agents across a variety of clinical settings is urgently required.

Thromboprophylaxis prescribing and thrombotic event rates in multiple myeloma patients treated with lenalidomide or thalidomide at a specialist cancer hospital

To assess thromboprophylaxis prescribing patterns against current guidelines and report thromboembolism (TE) incidence in multiple myeloma (MM) patients treated with thalidomide (thal) or lenalidomide (len) at a specialist cancer hospital over a one‐year period.

Pharmacist advice on the safety of Complementary and Alternative Medicines during conventional anticancer treatment

Complementary and alternative medicines (CAM) use is increasing, particularly in patients with a cancer diagnosis. When taken alone, many CAM are safe, but when taken concurrently with chemotherapy, radiotherapy or prior to surgery, serious side effects or interactions may occur.

A survey of manufacturing and handling practices for monoclonal antibodies by pharmacy, nursing and medical personnel

Introduction There is a paucity of data available to assess the occupational health and safety risk associated with exposure to monoclonal antibodies. Industry standards and published guidelines are conflicting or outdated. Guidelines offer contrary recommendations based on an array of methodological approaches. This survey aimed to describe current practices, beliefs and attitudes relating to the handling of monoclonal antibodies by Australian medical, nursing and pharmacy clinicians. Methods An electronic survey was distributed between June and September 2013. Respondents were surveyed on three focus areas: institutional guideline availability and content, current practices and attitudes. Demographic data relating to respondent and primary place of practice were also collected. Results A total of 222 clinicians completed the survey, with representation from all targeted professional groups and from a variety of geographic locations. 92% of respondents reported that their institution prepared or administered monoclonal antibodies, with 87% specifically handling anti-cancer monoclonal antibodies. Monoclonal antibodies were mostly prepared onsite (84–90%) and mostly within pharmacy clean-rooms (75%) and using cytotoxic cabinets (61%). 43% of respondents reported access to institutional monoclonal antibody handling guidelines with risk reduction strategies including training and education (71%), spill and waste management (71%), procedures for transportation (57%) and restricted handling (50%). Nurses had a stronger preference towards pharmacy manufacturing than both doctors and pharmacists for a range of clinical scenarios. 95% of all respondents identified that professional or regulatory body guidelines are an important resource when considering handling practices. Conclusion Monoclonal antibodies are most commonly handled according to cytotoxic drug standards and often in the absence of formal guidelines.

A systematic review of the impact of outpatient clinical pharmacy services on medication-related outcomes in patients receiving anticancer therapies:

Background Patients receiving anticancer therapies are frequently prescribed complex and high-risk medication regimens, which at times can result in medication misadventures. The objective of this review was to assess the effect of outpatient clinical pharmacy services on medication-related outcomes in patients receiving anticancer therapies, including patients undergoing radiotherapy. Methods A systematic review of original publications indexed in EMBASE, MEDLINE and Cochrane Library from June 2007 to June 2017. Eligible studies evaluated outpatient pharmacy clinic services for cancer patients and reported at least one medication-related quantitative outcome measure. Two authors independently reviewed full-text articles for inclusion, then extracted data and performed quality and risk of bias assessments. Results Of 908 identified publications, 13 met predefined eligibility criteria; 1 randomised control trial, 2 controlled cohort studies and 10 uncontrolled before–after studies. Many excluded studies described outpatient pharmacy services but lacked medication-related outcomes. All included studies had informative practice model designs, with interventions for drug-related problems including drug dose optimisation (nu2009=u20098), reduced drug interaction (nu2009=u20096) and adverse drug reaction reporting (nu2009=u20093). Most studies (nu2009=u200911) reported on symptom improvement, commonly nausea (nu2009=u20097) and pain (nu2009=u20095). Of four studies in radiotherapy cohorts, pharmacist involvement was associated with improved symptoms, satisfaction and wellbeing scores. Conclusion Few studies have objectively assessed outpatient pharmacy cancer services, even fewer in the radiotherapy settings. Although the results support these services, significant heterogeneity and bias in the study designs prohibit robust conclusions and further controlled trials are required.

Risk of thromboembolism with lymphoma: myth or reality?

Despite the availability of safe and efficacious antithrombotic agents, as well as the vast clinical experience justifying their use, thromboembolism (TE) remains a frequent complication among cancer patients, with substantial adverse health and economic consequences.[1] Cancer-associated thrombosis remains an important negative predictor of survival as well as a leading cause of death, and is associated with higher (2–3 fold) TE recurrence rates, higher (2–6 fold) bleeding complications on anticoagulant therapy, increased hospitalization and impaired quality of life.[2,3] Moreover, an incident TE event, once a cancer has been diagnosed and treatment started, often denotes a significant clinical hurdle, not only related to the morbidity and mortality associated with the TE event, but also the potential detrimental effect of an interruption or modification in therapy, attributable to the event and/or delivery of therapeutic anticoagulation. As such, risk-adapted primary thromboprophylaxis can have a substantial impact not only on TE reduction, but also disease response, survival, quality of life and healthcare resources. Much of the focus regarding prevention of cancer-associated TE has been with solid malignancies. However, recent studies, including Borg et al. in this issue of Leukemia and Lymphoma, have demonstrated that the risk of TE in patients with nonHodgkin lymphoma (NHL) is clinically relevant and that in appropriately risk-stratified populations, the observed risk is potentially comparable to other high TE risk subgroups.[4–12] In retrospective studies and pooled analyses, the reported incidence of TE among patients with NHL varies substantially from 1 to 15%. This variability in reported risk is largely due to the heterogeneity in patientand tumour-related factors (as well as therapy administered), with high grade lymphoma, such as diffuse large B-cell – including primary CNS and mediastinal lymphoma – conferring the highest rates.[5–7,10,11,13] A few prospective studies have equally demonstrated higher TE rates in DLBCL.[14,15] This burden of disease may well be underestimated, given the focus is generally on clinical macrovascular events and as such, under-appreciates the hemostatic, endothelial and inflammatory dysfunction that occurs at a microvascular level, which may still contribute to disease biology, morbidity and mortality. Risk stratification and predictive modeling tools, can be important enablers to facilitate the design of better targeted management strategies, to improve patient outcomes. Appropriate pharmacological thromboprophylaxis (P-TP) can reduce the rates of TE in up to 80% of at-risk patients, but this needs to be balanced against the potential serious complication of bleeding. Therefore the ability to identify patients, and the duration of risk, will allow a more personalized riskdirected approach, rather than the broad application in patients with lymphoma. Importantly, in all reported studies, the majority (>90%) of TE events among patients with NHL occur early, generally within three months from diagnosis, and during therapy.[4,8,9,12,13] The risk appears greatest in those patients with higher grade disease (i.e. DLBCL versus low grade lymphoma), primary CNS lymphoma, prior TE, more advanced stage disease, extra-nodal sites, increased BMI (>30 kg/m) and reduced performance status (ECOG 2–4).[4–9,11,12,15] Although this current study recognized only ECOG 2–4, advanced stage disease and prior TE event as predictors in multivariate analysis. An important limitation of this current study, and many studies to date, is the retrospective design and the limitation of source data to provide accurate assessment of proposed risk factors. Thrombosis Lymphoma (ThroLy) score was developed as a predictive tool for TE among patients with

Challenging historical perspectives of the 24-h chemotherapy day: Flexible chemotherapy dose-timing guidelines

Variation in dose‐timing within multiday chemotherapy regimens is largely unknown with convention being to administer subsequent days of treatment at 24‐h intervals. However, in reality there are many occasions where doses are given either earlier or later to accommodate a variety of clinical and operational priorities. This project aimed to evaluate the degree of existing variation in chemotherapy dose‐timing and to investigate whether deliberate variation could improve quality and efficiency outcomes such as reduction of after hours chemotherapy administration or reduced inpatient length of stay.

Does outpatient status really confer lower thrombotic risk

To the Editor, The 7th Biennial International Conference on Thrombosis and Haemostasis in Cancer (ICTHIC) was recently held in Bergamo, Italy. A key message from this congress was thatmorequality studies are required todirect thromboembolism (TE) preventive strategies in the ambulatory care (AC) setting. Some of the many high-quality scientific and clinical papers presented (conference proceedings available in Thrombosis Research 2014: 133, Suppl. 2) are summarised below to highlight this key issue. Anticancer care and therapy is increasingly being delivered in the AC setting, with a substantial burden of TEwell demonstrated in this forum, perhaps as high as the inpatient setting. 2 However, there is a lack of consensus in terms of expert guidance for TE prevention. Dr Garry Lyman presented the 2013 updated thromboprophylaxis guidelines from the American Society of Clinical Oncology (ASCO) recommending against routine pharmacologic thromboprophylaxis for AC patients. The American College of Chest Physicians (ACCP) recommend pharmacologic thromboprophylaxis for AC patients with TE risk factors who are at low risk of bleeding, and Italian guidelines specifically recommend pharmacologic thromboprophylaxis for lung and gastrointestinal cancer patients. 5 Wepresented our local research, surveyingAustralian clinicians involved in the delivery of care to lung cancer patients, and demonstrated the difficulty and uncertainty experienced by clinicians when considering thromboprophylaxis in the AC setting. Clinicians consistently identified patients with lung cancer receiving anticancer therapies as having a high thrombotic risk in both ambulatory and surgical settings, but with differences in recommendations and variation in practice. The concept of immobility and cancer-associatedTEwas also revisited in viewof the data from theRegistro Informatizado de la Enfermedad Tromboembólica (RIETE) Registry. Among more than 6000 patients with acute TE, 40% of those who suffered fatal pulmonary embolism had recent immobilisation (37%) or surgery (5.4%). Fatal pulmonary embolism was more commonly associated with immobilisation (5%, 95% confidence interval: 3.9–3.6) than surgery (0.8%, 95% confidence interval: 0.4–1.6). One in three patients dying of pulmonary embolism had recent immobilisation of ≥4 days; yet few immobilised patients received pharmacologic thromboprophylaxis (28%) compared to surgical patients (67%). In all, 58%of patientswere immobilised in the home, reinforcing the need for further studies in ‘ambulatory care’ settings. Whatdoesyourhospital guideline recommend?Popular opinion from the ICTHIC audience was that prioritisation of clinical data acquisition must supersede consensus guideline updates in order to improve patient care in this setting. The outpatient setting is increasingly the preferred treatment paradigm for anticancer care, reducing costs associated with hospitalisation and allowing patients to remain at home. TE is highly preventable yet remains the greatest cause of death in cancer patients aside from cancer itself; evidence-based models for TE prevention applicable to the AC setting are immediately required.