No abstract

Background Patients with cancer are managed across the whole healthcare spectrum. This complex system of interdependencies has high potential for errors to occur. This is a focus area for pharmacists, who possess the skillset to optimise cancer care across the health care system, identifying errors and other medication‐related problems (MRP). Aim The aim of this study was to identify and describe the impact of the pharmacist’s contribution in reducing cancer therapy‐related errors. Methods A search of English‐language publications in Embase, Medline and CINAHL was conducted. Databases were searched from 1 January 2010 until 29 September 2020 to identify all quantitative studies of a descriptive, observational or experimental design. Articles describing pharmacist‐led interventions in adults receiving one or more cancer therapies including oral chemotherapy, intravenous chemotherapy or immunotherapy compared to no intervention, usual care or a service delivered by another healthcare professional were included. Researchers screened articles to identify eligible studies, and then data were extracted using a standardised data collection sheet. Quality assessment was undertaken using the modified Cochrane and the Newcastle Ottawa risk of bias tools. Data were reported as number or percentage. Results Of 2292 papers identified, nine studies were eligible for inclusion in this review. Pharmacist interventions consistently showed an increased identification of medication errors and medication‐related problems. Pharmacist contributions in many of the included studies comprised medication reviews and monitoring, laboratory monitoring, adverse drug reaction and drug–drug interaction management, adherence monitoring and medication counselling. All studies showed pharmacist intervention in cancer care resulted in fewer errors compared to control arms. Error minimisation was described for parenteral and oral cancer therapies and also for supportive medications such as antiemetics. Conclusion Pharmacists reduce errors and potential patient harm in practice settings where cancer patients are treated. Pharmacists are an integral component of cancer care teams.

No abstract

The rate of invasive fungal infection (IFI) in patients with myelodysplasia (MDS) and acute myeloid leukemia (AML) receiving 5‐azacytidine is incompletely defined and published recommendations for mold‐active fungal prophylaxis in such patients vary according to source. We performed a retrospective cohort study in order to identify contemporary IFI rates and infection‐related mortality in relation to known risk factors and the use of antifungal prophylaxis. One hundred and seventeen patients receiving 5‐azacytidine for MDS and low blast count AML were identified, of whom 71 (61%) received antifungal prophylaxis. The IFI rate was 7.7% across the entire cohort: 5.6% in those receiving prophylaxis vs 10.9% in the subgroup who did not (P = .30). The presence of neutropenia at three months of treatment was associated with increased IFI risk (hazard ratio [HR] 8.29; (95% confidence interval [CI)] 1.61‐42.6; P = .01), and on multivariate analysis, IFI was independently associated with increased all‐cause mortality risk (HR 8.37; 95% CI 3.67 ‐ 19.11; P < .0001). These data further highlight the risk of IFI in this population and support the use of mold‐active prophylaxis in neutropenic patients receiving 5‐azacytidine for MDS and AML.

No abstract

Aim: Primary Central Nervous System Lymphoma (PCNSL) [i.e. diffuse large B-cell lymphoma of the CNS] is a rare and poor-prognosis disease occurring predominantly in older patients (median age &gt;60 years old). Prospective studies of two commonly used chemoimmunotherapy (CIT) protocols, MATRix and MPV/Ara-C (± rituximab), have reported 2-year PFS and OS of 57-61% and 69-81% respectively. Our aim was to evaluate registry-reported outcomes of frontline CIT strategies employed at Australasian sites. Method: A retrospective study of consecutive, immunocompetent, adult PCNSL patients (WHO criteria: 2017) treated with curative-intent CIT, from 10 sites (9 Australian, 1 Singaporean) between 1 st January 2009 and 31 st December 2018 (i.e. ten-year period). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier (log-rank) method. Univariate associations were derived using a Cox model with variables p&lt;0.10 entered stepwise into a multivariate model. Results: Data was collected on 207 patients, 189 of whom met WHO diagnostic criteria for PCNSL (i.e. diffuse large B-cell lymphoma of the CNS). We excluded patients with insufficient data (6), non-DLBCL histology (6), secondary PCNSL (3) and post-transplant lymphoproliferative disorder (3). Of these, 176 (93%) received curative-intent CIT. The majority (66%) were over 65 years of age (median: 65, range: 25-87); ECOG performance status was ≥ 2 in 31% (data not available for 14% of patients). The majority were male (55%) and had deep structure involvement (64%). International Extranodal Lymphoma Study Group (IELSG) risk criteria could not be calculated in many patients due to missing data (predominantly LDH and CSF protein). CSF involvement was rare (n=23, 13%) but data was only available for 60% of patients. Of the 159 with documented renal function, 26% had renal impairment (defined as Cockroft-Gault creatinine clearance &lt;60ml/min or eGFR &lt;90ml/min). Five CIT regimens were used: MATRix (n=16), MPV/Ara-C + rituximab (Rtx) (n=94), MBVP+- Rtx (n=11), MTX +-Rtx (n=31) and MTX/Ara-C +- Rtx (n=24). Intrathecal chemotherapy was used in only 29 patients (16%), and almost exclusively in combination with R-MPV. Median cumulative MTX dose was 17,500mg/m 2 (range: 1,000-64,000mg/m 2) and 69% received Ara-C (median dose: 12,000mg/m 2 [range: 1,000-44,000mg/m 2]). Eighty percent of patients achieved an overall response at the end of MTX therapy, with 52% achieving a complete response [data unavailable in n=29, 16%]. Estimated 2-year PFS and OS for the entire cohort were 54% (95%CI: 0.46-0.62) and 77% (95%CI: 0.70-0.83) respectively at a median follow-up of 2 years. Older patients (&gt;60yo) had shorter PFS but similar OS compared to their younger counterparts (2-year PFS: 47% vs 68%, p: 0.015, HR: 1.73, 95%CI: 1.11-2.70; 2-year OS: 74% vs 80%, p: 0.145, HR: 1.38, 95%CI: 0.81-2.33). R-MPV achieved superior PFS compared to MATRix although comparison was limited by low numbers in the MATRix cohort (n=16 vs n=94), likely reflective of the census period [2-year PFS: 74% vs 44% p: 0.025, HR 0.41, 95%CI 0.13-1.28]. Neither WBRT (n=57, 32%) nor ASCT (n=13, 7%) conferred a survival advantage but addition of rituximab (n=153, 87%) was associated with improved PFS (p: 0.007, HR: 0.47, 95%CI: 0.19-0.75). On multivariate analysis, type of induction CIT (p: 0.004, HR: 1.42, 95%CI: 1.23-1.42), cumulative MTX dose (p: 0.022, HR: 0.88, 95%CI: 0.83-0.94) and cumulative Ara-C dose (p: 0.016, HR: 0.76, 95%CI: 0.64-0.87) were associated with improved PFS. Cumulative MTX dose (p: 0.02, HR: 0.85, 95%CI: 0.78-0.92) and cumulative Ara-C dose (p: 0.007, HR: 0.67, 95%CI: 0.51-082) were also associated with improved OS. Conclusion: Registry-reported outcomes of contemporary CIT induction for PCNSL are favourable when compared to published trials and historical regimens. PCNSL with contemporary treatment should no longer be considered an invariably poor-prognostic disease. Data supports recent literature highlighting prognostic significance associated with maintenance of chemotherapy dose intensity (Martinez-Calle et al., Br J Haematol. 2020 Aug; 190(3):394-404. doi. 10.1111/bjh.16592). Figure 1 Figure 1. Disclosures Lewis: AstraZeneca: Consultancy, Honoraria; Janssen: Honoraria, Patents & Royalties: Conference attendance; Novartis: Patents & Royalties: Conference attendance; Roche: Consultancy, Honoraria. Gunjur: Myers Squibb: Honoraria. Ku: Roche: Consultancy; Antegene: Consultancy; Genor Biopharma: Consultancy. Wight: Jannsen: Honoraria, Other: Travel subsidies; Abbvie: Honoraria, Other: Travel subsidies. Shortt: Amgen: Research Funding; Astex: Research Funding; BMS: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees; Astellas: Membership on an entity's Board of Directors or advisory committees. Talaulikar: Roche: Honoraria, Research Funding; Jansenn: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Takeda: Honoraria, Research Funding; EUSA Pharma: Honoraria, Research Funding. Hawkes: Gilead: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees, Other: Travel and accommodation expenses, Research Funding, Speakers Bureau; Regeneron: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees; Merck Sharpe Dohme: Membership on an entity's Board of Directors or advisory committees; Janssen: Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Merck KgA: Research Funding; Bristol Myers Squib/Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Specialised Therapeutics: Consultancy; Antigene: Membership on an entity's Board of Directors or advisory committees. Cheah: MSD: Consultancy, Honoraria, Other: advisory, Research Funding; Janssen: Consultancy, Honoraria, Other: advisory; TG Therapeutics: Consultancy, Honoraria, Other: advisory; Roche: Consultancy, Honoraria, Other: advisory and travel expenses, Research Funding; Loxo/Lilly: Consultancy, Honoraria, Other: advisory; AstraZeneca: Consultancy, Honoraria, Other: advisory; Celgene: Research Funding; AbbVie: Research Funding; Beigene: Consultancy, Honoraria, Other: advisory; Ascentage pharma: Consultancy, Honoraria, Other: advisory; Gilead: Consultancy, Honoraria, Other: advisory. Opat: Merck: Honoraria, Membership on an entity's Board of Directors or advisory committees; 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. Gregory: Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel fees, Speakers Bureau; Janssen: Consultancy; Novartis: Consultancy.

Objective: The infection risk in patients receiving ibrutinib, idelalisib or venetoclax for chronic lymphocytic leukaemia (CLL) or B-cell lymphoma treated outside of clinical trials is incompletely defined. We sought to identify the severe infection rate and associated risk factors in a 'real-world' cohort. Methods:We conducted a retrospective cohort study of adult patients with CLL or lymphoma treated with ibrutinib, idelalisib or venetoclax. Results: Of 67 patients identified (ibrutinib n = 53, idelalisib n = 8 and venetoclax n = 6), 32 (48%) experienced severe infection. Severe infection occurred at a rate of 65 infections per 100 person-years, with a median of 17.8 months of therapy. Median time to first infection (IQR) was 5.4 months (1.4-15.9). Poor baseline Eastern Cooperative Oncology Group (ECOG) performance status and high Charlson Comorbidity Index (CCI) score associated with increased risk of severe infection [hazard ratios (95% CI) 1.57 (1.07-2.31, p = .018) and 1.3 (1.05-1.62, p = .016) respectively]. Conclusion:The severe infection rate for patients receiving ibrutinib, idelalisib or venetoclax for lymphoma and CLL exceeded those reported in clinical trials. Patients with poor ECOG or high CCI should be closely monitored for early signs of infection and prevention strategies actively pursued. Further prospective research is required to define optimal antimicrobial prophylaxis recommendations.