Clinical characteristics and outcomes of EZH2-mutant myelodysplastic syndrome: A large single institution analysis of 1774 patients.

EZH2 mutations in myeloid neoplasms are loss of function type, and have been linked to poor overall survival (OS) in patients with myelodysplastic syndrome (MDS). However, the specific determinants of outcomes in EZH2-mutant (mut) MDS are not well characterized. In this single-center retrospective study, clinical and genomic data were collected on 1774 patients with MDS treated at Moffitt Cancer Center. In our cohort, 83 (4.7%) patients had a pathogenic EZH2 mutation. Patients with EZH2mut MDS were older than EZH2-wild type (wt) group (median age- 72 vs. 69 years, p = 0.010). The most common co-occurring mutation in EZH2mut MDS was ASXL1, with a significantly higher frequency than EZH2wt (54% vs. 19%, p < 0.001). Patients with EZH2mut MDS had lower response rates to hypomethylating agents compared to EZH2wt MDS (26% vs. 39%; p = 0.050). Median OS of patients with EZH2mut MDS was 30.8 months, with a significantly worse OS than EZH2wt group (35.5 vs. 61.2 months, p = 0.003) in the lower-risk IPSS-R categories. Among patients with EZH2mut MDS, co-presence of ASXL1 or RUNX1 mutations was associated with inferior median OS compared to their wt counterparts (26.8 vs. 48.7 months, p = 0.031). Concurrent chromosome 7 abnormalities (12%) were also associated with significantly worse OS (median OS- 20.8 vs. 35.5 months, p = 0.002) in EZH2mut MDS. Future clinical trials should explore the potential role of novel targeted therapies in improving outcomes in patients with EZH2mut MDS.

Safety profiles of second-line tyrosine kinase inhibitors in patients with chronic myeloid leukaemia.

AIMS AND OBJECTIVES: To review the use of second-line tyrosine kinase inhibitors in patients with chronic myeloid leukaemia (CML) and provide recommendations for managing adverse events (AEs) to maximise patient benefit. BACKGROUND: Treatment of CML has been revolutionised with the advent of tyrosine kinase inhibitors (TKIs) that target the breakpoint cluster region-Abelson (BCR-ABL) kinase. Imatinib is the only first-line TKI currently available for the treatment of CML; however, intolerance and resistance remain significant clinical challenges. The approved second-line treatment options for CML are dasatinib, nilotinib or escalated-dose imatinib. DESIGN: Review article. METHODS: Searches of PubMed, ASCO and ASH electronic databases for relevant search terms were performed between July 2008-January 2009. FINDINGS: Dasatinib has no cross-intolerance with imatinib, and the most frequent AEs (cytopenias and pleural and pericardial effusions) can generally be managed by dose interruption and reduction. Nilotinib has a high degree of haematologic cross-intolerance with first-line imatinib. As might be expected, high-dose imatinib has the potential for more severe AEs than standard-dose imatinib. CONCLUSIONS: There are known safety issues inherent to each TKI and close monitoring by nursing staff is necessary to identify and effectively manage AEs. RELEVANCE TO CLINICAL PRACTICE: All three TKIs have demonstrated potential for fluid retention and cardiotoxicity. Nurses should be aware of how these AEs manifest and intervene appropriately. The safety profiles of these TKIs clearly differs and it is important to consider factors such as comorbidities when making treatment decisions.

Transitioning Patients With Iron Overload From Exjade to Jadenu.

Iron overload is a concern for patients who require chronic transfusions as a result of inherited or acquired anemias, including sickle cell disease, thalassemia, and myelodysplastic syndromes. Iron chelation therapy (ICT) is the primary treatment for iron overload in these patients. The ICT deferasirox, which has been available as an oral dispersible tablet for liquid suspension, is now also available as a once-daily, film-coated tablet (FCT). Deferasirox FCT allows greater convenience and may be associated with fewer gastrointestinal side effects versus the original formulation. Dose adjustment increments, determined by titration monitoring, are lower for the FCT because of greater bioavailability.

Potential of Biosimilars to Increase Access to Biologics: Considerations for Advanced Practice Providers in Oncology.

Biosimilars are biologic products that are highly similar, but not identical, to a licensed reference (or "originator") biologic product. These agents have the potential to provide efficiencies and improve access to treatment for patients. Biosimilars are currently available for use in clinical practice, including oncology indications, and several more are in clinical development. Due to several key differences in their fundamental properties, production and manufacturing of biosimilars is more complex compared with that of small-molecule generic drugs. Accordingly, the generic drug approval process is not suitable or transferable to biosimilars, the approval of which involves extensive and thorough comparison with the originator biologic. Advanced practice providers play an important role in evaluating treatment options available to patients, prescribing, patient education, and product monitoring. In order to perform these tasks effectively, advanced practice providers should understand the concepts related to biosimilars in clinical practice, particularly regarding extrapolation to other indications, product labeling, interchangeability between products, and routine pharmacovigilance, among other clinical considerations. However, many health-care providers have limited awareness and minimal experience regarding biosimilars. Thus, the purpose of this review is to provide an overview of biosimilars and discuss the clinical considerations for oncology advanced practice providers concerning these therapies.

Treatment Choices: A Quality of Life Comparison in Acute Myeloid Leukemia and High-risk Myelodysplastic Syndrome.

BACKGROUND: In the present exploratory, observational study, we compared the effect of intensive versus nonintensive treatment on quality of life for patients aged ≥ 60 years diagnosed with acute myeloid leukemia or high-risk myelodysplastic syndrome at 1 month after treatment. PATIENTS AND METHODS: A total of 73 patients with acute myeloid leukemia or high-risk myelodysplastic syndrome who had been treated at the inpatient and outpatient malignant hematology at Moffitt Cancer Center, a National Cancer Institute-designated comprehensive cancer center, were included. Two paired measurements of self-reported quality of life were used, 1 before treatment and 1 at 1 month after treatment to compare intensive versus nonintensive treatment. Patients completed the Functional Assessment of Cancer Therapy-Leukemia version for the quality-of-life measurement. Repeated measures analysis of variance was used to compare the effect of treatment and time and the interaction of treatment and time. The main research variables were intensive versus nonintensive treatment as the independent variable and quality of life measured using the Functional Assessment of Cancer Therapy-Leukemia version as the dependent variable. RESULTS: Physical function and leukemia symptoms improved for patients treated with intensive chemotherapy. A trend was found for improved quality of life for the intensive treatment compared with nonintensive treatment, for which the quality of life was stable at 1 month. CONCLUSION: The study participants treated with inpatient, induction chemotherapy experienced statistically significant improvement in their quality of life at 1 month. The outpatient, nonintensive study participants had stable quality of life at 1 month.

Practical Management of Lenalidomide-Related Rash.

Lenalidomide (LEN) is an immunomodulatory drug with US Food and Drug Administration approval for use in myelodysplastic syndromes (MDS), multiple myeloma (MM), and mantle cell lymphoma (MCL). The toxicity profile for LEN is similar across indications, with the most common adverse events reported in registration trials being hematologic in nature, and Grade ≥ 3 hematologic toxicities the most common reasons for treatment interruption or permanent LEN discontinuation. However, an analysis of the Celgene Global Drug Safety database showed that nonserious rash was the leading cause of permanent early discontinuation of LEN in patients with MDS treated in the postmarketing setting (similar data not available for patients with MM or MCL). In registration trials, rash was reported in up to a third of patients, but Grade ≥ 3 rash was uncommon and rash rarely led to LEN treatment interruption or permanent discontinuation. This suggests differences in management of LEN-related rash in clinical trials versus real-world use. Most LEN-related rash is mild to moderate in severity and might present as patchy, raised, macular skin lesions, sometimes with localized urticaria, which might be associated with pruritus. Mild to moderate rash might be treated with topical corticosteroids and/or oral antihistamines. Any grade LEN-related rash should be appropriately managed through awareness of symptoms, appropriate and prompt intervention, and maximizing patient self-reporting of early signs of rash using upfront educational initiatives. This guide to management of LEN-related rash reviews key clinical data from registration trials, and the incidence and physiology of LEN-related rash, grading of rash, and guidelines for patients and caregivers.