Practice patterns and real-life outcomes for patients with acute promyelocytic leukemia in the United States.

Acute promyelocytic leukemia (APL) is associated with a favorable long-term prognosis if appropriate treatment is initiated promptly. Outcomes in clinical trials and population-based registries vary; potential explanations include a delay in treatment and lower adherence to guideline-recommended therapy in real-world practice. We used the Vizient Clinical Data Base to describe demographic characteristics, baseline clinical characteristics, and treatment patterns in patients newly diagnosed with APL during the study period of April 2017 to March 2020. Baseline white blood cell count was used to assign risk status and assess treatment concordance with National Comprehensive Cancer Network guidelines. Logistic regression models examined adjusted associations between patient, hospital, disease characteristics, and adverse outcomes (in-hospital death or discharge to hospice). Among 1464 patients with APL, 205 (14.0%) experienced an adverse outcome. A substantial subset (20.6%) of patients did not receive guideline-concordant regimens. Odds of adverse outcomes increased with failure to receive guideline-concordant treatment (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.43-3.75; P = .001), high-risk disease (OR, 2.48; 95% CI, 1.53-4.00; P < .001), and increasing age (≥60 years: OR, 11.13; 95% CI, 4.55-27.22; P < .001). Higher hospital acute myeloid leukemia (AML) patient volume was associated with lower odds of adverse outcome (OR, 0.44; 95% CI, 0.20-0.99 [for ≤50 vs >200 AML patients per year]; P = .046). In conclusion, in this large database analysis, 14.0% of patients newly diagnosed with APL died or were discharged to hospice. A substantial proportion of patients did not receive guideline-concordant therapy, potentially contributing to adverse outcomes.

Evolving therapies for lower-risk myelodysplastic syndromes.

The development in the therapeutic landscape of myelodysplastic syndromes (MDS) has substantially lagged behind other hematologic malignancies with no new drug approvals for MDS for 13 years since the approval of decitabine in the United States in 2006. While therapeutic concepts for MDS patients continue to be primarily defined by clinical-pathologic risk stratification tools such as the International Prognostic Scoring System (IPSS) and its revised version IPSS-R, our understanding of the genetic landscape and the molecular pathogenesis of MDS has greatly evolved over the last decade. It is expected that the therapeutic approach to MDS patients will become increasingly individualized based on prognostic and predictive genetic features and other biomarkers. Herein, we review the current treatment of lower-risk MDS patients and discuss promising agents in advanced clinical testing for the treatment of symptomatic anemia in lower-risk MDS patients such as luspatercept and imetelstat. Lastly, we review the clinical development of new agents and the implications of the wider availability of mutational analysis for the management of individual MDS patients.

Beyond Ruxolitinib: Fedratinib and Other Emergent Treatment Options for Myelofibrosis.

Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by clonal proliferation of differentiated myeloid cells leading to bone marrow fibrosis, cytopenias and extramedullary hematopoiesis. In late 2019, the FDA approved the highly selective JAK2 inhibitor, fedratinib, for intermediate-2 or high-risk primary or secondary MF, making it the second drug approved for MF after ruxolitinib, a JAK1/2 inhibitor, which was approved for MF in 2011. The approval of fedratinib was based on phase II trials and the phase III JAKARTA trial, in which the drug significantly reduced splenomegaly and symptom burden compared to placebo, including some patients previously treated with ruxolitinib. The main side effects of fedratinib include anemia, gastrointestinal symptoms, and elevations in liver transaminases. Fedratinib also has ablack box warning for encephalopathy, although this occurred only in about 1% of the treated patients, most of which were ultimately felt not to represent Wernicke's encephalopathy. Nonetheless, monitoring of thiamine levels and supplementation are recommended especially in high-risk patients. This concern has led to a prolonged clinical hold and delayed the drug approval by several years during which the drug exchanged manufacturers, highlighting the need for meticulous investigation and adjudication of serious, but rare, adverse events in drug development that could end up preventing drugs with favorable risk/benefit ratio from being approved. In this review, we discuss the pharmacokinetic data and efficacy, as well as the toxicity results of clinical trials of fedratinib. We also review ongoing trials of JAK inhibitors in MF and explore future treatment options for MF patients who are refractory to ruxolitinib.