NEDD8 and HDACs: promising cotargets in AML.

Abstract

adverse events (40% and 39%, respectively). In contrast, 4 cycles of ABVD was associated with a considerably higher rate of early treatment termination (18%) and grade 3-4 toxicity (65%). With regard to bleomycininduced lung toxicity, 0% and 1.5% cases were reported among patients receiving 2 cycles of AVD and ABVD, respectively, whereas 7 cases (10%) were reported among patients receiving 4 cycles ABVD, 3 of which were fatal. In applying this data to the care of older patients with HL, it is important to note that most patients included in this analysis had good performance status (most with Eastern Cooperative Oncology Group grade 0 or 1) and were fairly young in age (median age, 64-66 years). Furthermore, as mentioned by the authors, comprehensive geriatric assessments were not included in the HD10 or HD13 studies, therefore the impact of factors such as functional status, fall risk, and social support on treatment toxicity within these studies is not known. In the retrospective analysis by Evens et al, age 70 (or greater) and loss of activities of daily living were the most important adverse prognostic factors in this patient population. Ongoing and future prospective studies will determine whether these factors predict for treatment toxicity and need to be considered when deciding upon treatment courses. Current studies for elderly patients incorporating novel agents for HL, such as the ongoing study with sequential brentuximab vedotin and AVD (clinicaltrials.gov #NCT01476410) may obviate the need for bleomycin in this population. For now, though, this analysis from the GHSG provides us with a framework for using bleomycin in older patients (see figure). At the very least, we should aim to use no more than 2 cycles of chemotherapy with bleomycin for older HL patients. In early-stage disease, this is accomplished by using radiation consolidation to shorten the course of chemotherapy. In advanced-stage disease, it is appropriate to treat as per the response-adjusted therapy for HL study, in which patients with PET-2–negative scans had bleomycin removed after 2 cycles of ABVD with no adverse impact on tumor control. As the authors mention, known risk factors for bleomycin toxicity, such as underlying lung disease, renal insufficiency, pulmonary radiation, and the tobacco history could not be assessed in their analysis due to the small numbers; however, the use of bleomycin for patients with these comorbities should likely be avoided altogether. Ongoing and future prospective studies, which incorporate comprehensive geriatric assessments and novel HL agents, are likely to facilitate the development of risk-adapted treatment approaches for older patients with HL and hopefully improve outcomes for this group. Conflict-of-interest disclosure: A.M. received research funding from Seattle Genetics. n

DOI: 10.1182/blood-2016-02-699058

Cite this paper

@article{Bhalla2016NEDD8AH, title={NEDD8 and HDACs: promising cotargets in AML.}, author={Kapil N. Bhalla and Warren Fiskus}, journal={Blood}, year={2016}, volume={127 18}, pages={2168-70} }