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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Lenalidomide and prednisone for myelofibrosis: Eastern Cooperative Oncology Group (ECOG) phase 2 trial E4903
Ruben A Mesa1, Xiaopan Yao, Larry D Cripe
1Mayo Clinic, Scottsdale, AZ, USA. mesa.ruben@mayo.edu
Abstract:
A multicenter Eastern Cooperative Group (ECOG) phase 2 trial assessed whether adding prednisone to lenalidomide would improve previously reported responses in persons with myelofibrosis (MF). Forty-eight subjects with anemia (42 evaluable) received lenalidomide, 10 mg/d, with a 3-month low-dose prednisone taper. Ten subjects received 3 months, and 25 received 6 months of therapy. Myelosuppression was the main toxicity with 88% with ≥ grade 3 hematologic toxicity and 45% ≥ grade 3 nonhematologic toxicity. There were responses in 10 subjects (23%) using the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT)-defined clinical improvement of anemia in 8 (19%) and/or decreased spleen size in 4 (10%). Serial bone marrow analysis showed no resolution of disease-related fibrosis or angiogenesis. With a median follow-up of 2.3 years, 23 subjects are alive. Lenali-domide and prednisone for myelofibro-sis evaluated through a multicentered-cooperative group mechanism is only modestly active and myelosuppre-sive. This study was registered at http://clinicaltrials.gov as NCT00227591.
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Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...