Sara Tinsley

Phase II clinical study of erlotinib for treatment of myelodysplastic syndromes.

Outcome in patients with myelodysplastic syndrome (MDS) after azanucleoside failure is poor with unmet need for active novel agents. Preclinical data have suggested that erlotinib has in vivo and in vitro off epidermal growth factor receptor (EGFR)‐target activity in MDS. We conducted a phase II study with single‐agent erlotinib 150 mg/day orally in MDS patients following azanucleoside failure. All intermediate‐2 or high‐risk MDS patients by International Prognostic Scoring System and only those low/intermediate‐1 patients with transfusion‐dependent anemia or platelet counts <50 × 109/L or a significant clinical hemorrhage requiring platelet transfusion or ANC <1 × 109/L were eligible, with most of our patients being at high risk. In 35 eligible patients, overall best response was 14% (3 patients having marrow complete response and 2 hematological improvement). Four deaths occurred on study (sepsis, intracranial hemorrhage, sudden death, and acute myeloid leukemia (AML)). The most common observed grade 3/4 toxicities according to CTCAE v3 were diarrhea (17.1%), rash (17.1%), and infection (11.6%), accompanied by fatigue, thrombocytopenia, and anorexia at 5.7% each. Median overall survival was 6.8 months (95% CI 4.9–13.2), and leukemia‐free survival was 5 months (95% CI 3.4–7.3). Erlotinib was generally well tolerated, with modest single‐agent activity. Given these results and preclinical data suggesting synergistic effect with azanucleosides, the combination should be further explored. Am. J. Hematol. 89:809–812, 2014.

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.

Caring for Patients with Chronic Myeloid Leukemia (CML) Receiving Tyrosine Kinase Inhibitor (TKI) Therapy in an Era of Evolving Treatment Goals

S224 CML-121 Predictors of Success in Treatment-Free Remission: A Single Centre Experience Naranie Shanmuganathan , Susan Branford, Agnes Yong, Devendra Hiwase, David Yeung, David Ross, Timothy Hughes Department of Haematology, Royal Adelaide Hospital, Adelaide, South Australia, Australia; Department of Haematology, SA Pathology, Adelaide, South Australia, Australia; Department of Genetics and Molecular Pathology, SA Pathology, Adelaide, South Australia, Australia; Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, Australia; Department of Haematology, Flinders Medical Centre, Adelaide, South Australia, Australia; Cancer Theme, South Australian Health & Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia; Adelaide Cancer Centre, Adelaide, South Australia, Australia; School of Pharmacy and Medical Science, University of South Australia, Adelaide, South Australia, Australia; School of Medicine, University of Adelaide, Adelaide, South Australia, Australia; School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia; School of Medicine, Flinders University, Adelaide, South Australia, Australia

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. Micro‐Abstract The results of the present pilot study can be used to counsel older patients with acute myeloid leukemia and high‐risk myelodysplastic syndrome regarding treatment choices that will align with their goals for their quality of life. Future studies are needed with a larger and more diverse patient sample to address whether the more intensive treatment approach improves patients’ quality of life.